Bipolar disorder not otherwise specified (BD-NOS) is a diagnosis for bipolar disorder (BD) when it does not fall within the other established sub-types.
Bipolar disorder NOS is sometimes referred to as subthreshold bipolar disorder.
BD-NOS is a mood disorder and one of three subtypes on the bipolar spectrum, which also includes bipolar I disorder and bipolar II disorder. BD-NOS was a classification in the DSM-IV and has since been changed to Bipolar “Other Specified” and “Unspecified” in the 2013 released DSM-5.
Bipolar disorder is difficult to diagnose. If a person displays some symptoms of bipolar disorder but not others, the clinician may diagnose bipolar NOS. The diagnosis of bipolar NOS is indicated when there is a rapid change (days) between manic and depressive symptoms and can also include recurring episodes of hypomania. Bipolar NOS may be diagnosed when it is difficult to tell whether bipolar is the primary disorder due to another general medical condition, such as a substance use disorder.
Individual approaches to treatment are recommended, usually involving a combination of mood stabilisers and atypical antipsychotics. Psychotherapy may be beneficial and should be started early.
Tranylcypromine (sold under the trade name Parnate among others) is a monoamine oxidase inhibitor (MAOI); more specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO).
Tranylcypromine is a propylamine formed from the cyclisation of amphetamine’s side chain; therefore, it is classified as a substituted amphetamine.
Tranylcypromine was originally developed as an analogue of amphetamine. Although it was first synthesized in 1948, its MAOI action was not discovered until 1959. Precisely because tranylcypromine was not, like isoniazid and iproniazid, a hydrazine derivative, its clinical interest increased enormously, as it was thought it might have a more acceptable therapeutic index than previous MAOIs.
The drug was introduced by Smith, Kline and French in the United Kingdom in 1960, and approved in the United States in 1961. It was withdrawn from the market in February 1964 due to a number of patient deaths involving hypertensive crises with intracranial bleeding. However, it was reintroduced later that year with more limited indications and specific warnings of the risks.
Tranylcypromine is used to treat major depressive disorder, including atypical depression, especially when there is an anxiety component, typically as a second-line treatment. It is also used in depression that is not responsive to reuptake inhibitor antidepressants, such as the SSRIs, TCAs, or bupropion.
Cardiovascular or cerebrovascular disease.
Tyramine, found in several foods, is metabolized by MAO. Ingestion and absorption of tyramine causes extensive release of norepinephrine, which can rapidly increase blood pressure to the point of causing hypertensive crisis.
Concomitant use of serotonin-enhancing drugs, including SSRIs, serotonergic TCAs, dextromethorphan, and meperidine may cause serotonin syndrome.
Concomitant use of MRAs, including fenfluramine, amphetamine, and pseudoephedrine may cause toxicity via serotonin syndrome or hypertensive crisis.
L-DOPA given without carbidopa may cause hypertensive crisis.
Tyramine is a common component in many foods, and is normally rapidly metabolised by MAO-A. Individuals not taking MAOIs may consume at least 2 grams of tyramine in a meal and not experience an increase in blood pressure, whereas those taking MAOIs such as tranylcypromine may experience a sharp increase in blood pressure following consumption of as little as 10 mg of tyramine, which can lead to hypertensive crisis.
Foods containing tyramine include aged cheeses, cured meats, tofu and certain red wines. Some, such as yeast extracts, contain enough tyramine to be potentially fatal in a single serving. Spoiled food is also likely to contain dangerous levels of tyramine.
Incidence of Adverse Effects
Very common (>10% incidence) adverse effects include:
Dizziness secondary to orthostatic hypotension (17%).
Common (1-10% incidence) adverse effects include:
Weight loss (2%).
Dry mouth (2%).
Sexual function disorders (2%).
Hypertension (1-2 hours after ingestion) (2%).
Urinary retention (2%).
Other (unknown incidence) adverse effects include:
Sensation of cold.
Of note, there has not been found to be a correlation between sex and age below 65 regarding incidence of adverse effects.
Tranylcypromine is not associated with weight gain and has a low risk for hepatotoxicity compared to the hydrazine MAOIs.
It is generally recommended that MAOIs be discontinued prior to anaesthesia; however, this creates a risk of recurrent depression. In a retrospective observational cohort study, patients on tranylcypromine undergoing general anaesthesia had a lower incidence of intraoperative hypotension, while there was no difference between patients not taking an MAOI regarding intraoperative incidence of bradycardia, tachycardia, or hypertension. The use of indirect sympathomimetic drugs or drugs affecting serotonin reuptake, such as meperidine or dextromethorphan poses a risk for hypertension and serotonin syndrome respectively; alternative agents are recommended. Other studies have come to similar conclusions. Pharmacokinetic interactions with anaesthetics are unlikely, given that tranylcypromine is a high-affinity substrate for CYP2A6 and does not inhibit CYP enzymes at therapeutic concentrations.
Tranylcypromine abuse has been reported at doses ranging from 120-600 mg per day. It is thought that higher doses have more amphetamine-like effects and abuse is promoted by the fast onset and short half-life of tranylcypromine.
Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.
Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.
In addition to contraindicated concomitant medications, tranylcypromine inhibits CYP2A6, which may reduce the metabolism and increase the toxicity of substrates of this enzyme, such as:
TSNAs (found in cured tobacco products, including cigarettes).
Norepinephrine reuptake inhibitors prevent neuronal uptake of tyramine and may reduce its pressor effects.
Tranylcypromine acts as a nonselective and irreversible inhibitor of monoamine oxidase. Regarding the isoforms of monoamine oxidase, it shows slight preference for the MAOB isoenzyme over MAOA. This leads to an increase in the availability of monoamines, such as serotonin, norepinephrine, and dopamine, as well as a marked increase in the availability of trace amines, such as tryptamine, octopamine, and phenethylamine. The clinical relevance of increased trace amine availability is unclear.
It may also act as a norepinephrine reuptake inhibitor at higher therapeutic doses. Compared to amphetamine, tranylcypromine shows low potency as a dopamine releasing agent, with even weaker potency for norepinephrine and serotonin release.
Tranylcypromine has also been shown to inhibit the histone demethylase, BHC110/LSD1. Tranylcypromine inhibits this enzyme with an IC50 < 2 μM, thus acting as a small molecule inhibitor of histone demethylation with an effect to de-repress the transcriptional activity of BHC110/LSD1 target genes. The clinical relevance of this effect is unknown.
Tranylcypromine has been found to inhibit CYP46A1 at nanomolar concentrations. The clinical relevance of this effect is unknown.
Tranylcypromine reaches its maximum concentration (tmax) within 1-2 hours. After a 20 mg dose, plasma concentrations reach at most 50-200 ng/mL. While its half-life is only about 2 hours, its pharmacodynamic effects last several days to weeks due to irreversible inhibition of MAO.
Metabolites of tranylcypromine include 4-hydroxytranylcypromine, N-acetyltranylcypromine, and N-acetyl-4-hydroxytranylcypromine, which are less potent MAO inhibitors than tranylcypromine itself. Amphetamine was once thought to be a metabolite of tranylcypromine, but has not been shown to be.
Tranylcypromine inhibits CYP2A6 at therapeutic concentrations.
Tranylcypromine is known to inhibit LSD1, an enzyme that selectively demethylates two lysines found on histone H3. Genes promoted downstream of LSD1 are involved in cancer cell growth and metastasis, and several tumour cells express high levels of LSD1. Tranylcypromine analogues with more potent and selective LSD1 inhibitory activity are being researched in the potential treatment of cancers.
Tranylcypromine may have neuroprotective properties applicable to the treatment of Parkinson’s disease, similar to the MAO-B inhibitors selegiline and rasagiline. As of 2017, only one clinical trial in Parkinsonian patients has been conducted, which found some improvement initially and only slight worsening of symptoms after a 1.5 year follow-up.
Depression is a symptom of some physical diseases; a side effect of some drugs and medical treatments; and a symptom of some mood disorders such as major depressive disorder or dysthymia. Physical causes are ruled out with a clinical assessment of depression that measures vitamins, minerals, electrolytes, and hormones. Management of depression may involve a number of different therapies: medications, behaviour therapy, psychotherapy, and medical devices.
Though psychiatric medication is the most frequently prescribed therapy for major depression, psychotherapy may be effective, either alone or in combination with medication. Combining psychotherapy and antidepressants may provide a “slight advantage”, but antidepressants alone or psychotherapy alone are not significantly different from other treatments, or “active intervention controls”. Given an accurate diagnosis of major depressive disorder, in general the type of treatment (psychotherapy and/or antidepressants, alternate or other treatments, or active intervention) is “less important than getting depressed patients involved in an active therapeutic program.”
Psychotherapy is the treatment of choice in those under the age of 18, with medication offered only in conjunction with the former and generally not as a first line agent. The possibility of depression, substance misuse or other mental health problems in the parents should be considered and, if present and if it may help the child, the parent should be treated in parallel with the child.
Psychotherapy and Behaviour Therapy
There are a number of different psychotherapies for depression which are provided to individuals or groups by psychotherapists, psychiatrists, psychologists, clinical social workers, counsellors or psychiatric nurses. With more chronic forms of depression, the most effective treatment is often considered to be a combination of medication and psychotherapy. Psychotherapy is the treatment of choice in people under 18. A meta-analysis examined the effectiveness of psychotherapy for depression across ages from younger than 13 years to older than 75 years. It summarizes results from 366 trials included 36,702 patients. It found that the best results were for young adults, with an average effect size of g=.98 (95% CI, 0.79-1.16). The effects were smallest for young children (<13 years), g = .35 (95% CI, 0.15-0.55), and second largest in the oldest group, g = .97 (95% CI, 0.42-1.52). The study was not able to compare the different types of therapy to each other. Most of the studies with children used therapies originally developed with adults, which may have reduced the effectiveness. The greater benefits with young adults might be due to a large number of studies including college students, who might have an easier time learning therapy skills and techniques. Most of the studies in children were done in the USA, whereas in older age groups, more balanced numbers of studies came from Europe and other parts of the world as well.
As the most studied form of psychotherapy for depression, cognitive behavioural therapy (CBT) is thought to work by teaching clients to learn a set of cognitive and behavioural skills, which they can employ on their own. Earlier research suggested that cognitive behavioural therapy was not as effective as antidepressant medication in the treatment of depression; however, more recent research suggests that it can perform as well as antidepressants in treating patients with moderate to severe depression. Beck’s treatment manual, Cognitive therapy of depression, has undergone the most research and accumulated the most evidence for its use. However, a number of other CBT manuals also have evidence to support their effectiveness with depression.
The effect of psychotherapy on patient and clinician rated improvement as well as on revision rates have declined steadily from the 1970s.
A systematic review of data comparing low-intensity CBT (such as guided self-help by means of written materials and limited professional support, and website-based interventions) with usual care found that patients who initially had more severe depression benefited from low-intensity interventions at least as much as less-depressed patients.
For the treatment of adolescent depression, one published study found that CBT without medication performed no better than a placebo, and significantly worse than the antidepressant fluoxetine. However, the same article reported that CBT and fluoxetine outperformed treatment with only fluoxetine. Combining fluoxetine with CBT appeared to bring no additional benefit in two different studies or, at the most, only marginal benefit, in a fourth study.
Behaviour therapy for depression is sometimes referred to as behavioural activation. Studies exist showing behavioural activation to be superior to CBT. In addition, behavioural activation appears to take less time and lead to longer lasting change. Two well-researched treatment manuals include Social skills training for depression and Behavioural activation treatment for depression.
Emotionally focused therapy, founded by Sue Johnson and Les Greenberg in 1985, treats depression by identifying and processing underlying emotions. The treatment manual, Facilitating emotional change, outlines treatment techniques.
Acceptance and commitment therapy (ACT), a mindfulness form of CBT, which has its roots in behaviour analysis, also demonstrates that it is effective in treating depression, and can be more helpful than traditional CBT, especially where depression is accompanied by anxiety and where it is resistant to traditional CBT.
A review of four studies on the effectiveness of mindfulness-based cognitive therapy (MBCT), a recently developed class-based program designed to prevent relapse, suggests that MBCT may have an additive effect when provided with the usual care in patients who have had three or more depressive episodes, although the usual care did not include antidepressant treatment or any psychotherapy, and the improvement observed may have reflected non-specific or placebo effects. Of note, although Mindfulness-based cognitive therapy for depression prevented relapse of future depressive episodes, there is no research on whether it can cause the remission of a current depressive episode.
Interpersonal psychotherapy (IPT) focuses on the social and interpersonal triggers that may cause depression. There is evidence that it is an effective treatment for depression. Here, the therapy takes a fairly structured course (often 12 sessions, as in the original research versions) as in the case with CBT; however, the focus is on relationships with others. Unlike family therapy, IPT is an individual format, so it is possible to work on interpersonal themes even if other family members do not come to the session. Therapy can be used to help a person develop or improve interpersonal skills in order to allow him or her to communicate more effectively and reduce stress. In a meta-analysis of 16 studies and 4,356 patients, the average improvement in depressive symptoms was an effect size of d = 0.63 (95% CI, 0.36 to 0.90). IPT combined with pharmacotherapy was more effective in preventing relapse than pharmacotherapy alone, number needed to treat = 7.63.
Psychoanalysis, a school of thought founded by Sigmund Freud that emphasizes the resolution of unconscious mental conflicts, is used by its practitioners to treat clients presenting with major depression. A more widely practiced technique, called psychodynamic psychotherapy, is loosely based on psychoanalysis and has an additional social and interpersonal focus. In a meta-analysis of three controlled trials, psychodynamic psychotherapy was found to be as effective as medication for mild to moderate depression.
Shared decision making is an approach whereby patients and clinicians freely share important evidence when tasked with decision making and where patients are guided to consider the best available options to make an informed decision. The principles are well documented, but there is a gap in that it’s hard to apply them in routine clinical practice. The steps have been simplified into five steps. The first step is seeking patient participation in that the health practitioner is tasked with communicating existing choices and therefore inviting them to the decision making process. The next step involves assisting the patient to explore and compare the treatment options by a critical analysis of the risks and benefits. The third step involves the assessment of the patient’s values and what they prefer taking to account what is of paramount urgency to the patient. Step 4 involves decision making where the patient and the practitioner make a conclusive decision on the best option and arrange for subsequent follow up meetings. Finally, the fifth step involves the analysis of the patient’s decision’. Five steps for you and your patients to work together to make the best possible health care decisions. The step involves monitoring of the degree of implementation, overcoming of barriers of decision implantation consequently the decisions need to be revisited and optimised thus ensuring the decision has a positive impact on health outcomes its success relies on the ability of the health practitioner to create a good interpersonal relationship with the patient.
Depression still remains a major problem in the US whereby statistics have it that 16 million people were affected in the year 2017. The depression is multifactorial and has been on the increase due to societal pressure, genetic association and increase in use of drugs. incorporation of nursing in management of depression may seem important in that nursing holds a pivotal role in health care delivery where they are the health practitioners that have been trained to be versatile from clinical to psychological care. Their incorporation in shared decision making in treating depression may be important as nurses are known to have the best interpersonal relationship with the patients thus a better collaborative model can be achieved due to this fact. With this in mind, the nurses may serve to administer drugs in management, prepare and maintain the patient’s records, interaction with other care staff to achieve optimum care, and organising therapy sessions. In a study another study concerning shared decision-making interventions for people with mental health conditions there were no overt benefits that were discovered and the called for further research in this area. Another study found that it is important to begin the dissemination and implementation of SDM as they proved that it has benefits in healthcare especially in mental health care and has received social and government support and however transitioning to SDM has proven to be an uphill task. It has been suggested that SDM is of importance in demonstrating patient preferences in decision making when there is no clear approach to treatment. In addition, numerous tools can be used to make the decision making the process easier these include the Controlled Preferences Scale that informs clinicians on how to actively involve patients
Commentators suggest that providers need to embrace shared decision making by making sure that patients participate actively in their management thus enabling the success of the model.
To find the most effective pharmaceutical drug treatment, the dosages of medications must often be adjusted, different combinations of antidepressants tried, or antidepressants changed. Norepinephrine reuptake inhibitor (NRIs) can be used as antidepressants. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft, Lustral), escitalopram (Lexapro, Cipralex), fluoxetine (Prozac), paroxetine (Seroxat), and citalopram, are the primary medications considered, due to their relatively mild side effects and broad effect on the symptoms of depression and anxiety, as well as reduced risk in overdose, compared to their older tricyclic alternatives. Those who do not respond to the first SSRI tried can be switched to another. If sexual dysfunction is present prior to the onset of depression, SSRIs should be avoided. Another popular option is to switch to the atypical antidepressant bupropion (Wellbutrin) or to add bupropion to the existing therapy; this strategy is possibly more effective. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating noradrenergic and specific serotonergic antidepressant (NaSSA) antidepressant mirtazapine (Zispin, Remeron) can be used in such cases. CBT for Insomnia can also help to alleviate the insomnia without additional medication. Venlafaxine (Effexor) from the SNRI class may be moderately more effective than SSRIs; however, it is not recommended as a first-line treatment because of the higher rate of side effects, and its use is specifically discouraged in children and adolescents. Fluoxetine is the only antidepressant recommended for people under the age of 18, though, if a child or adolescent patient is intolerant to fluoxetine, another SSRI may be considered. Evidence of effectiveness of SSRIs in those with depression complicated by dementia is lacking.
Tricyclic antidepressants (TCAs) have more side effects than SSRIs (but less sexual dysfunctions) and are usually reserved for the treatment of inpatients, for whom the tricyclic antidepressant amitriptyline, in particular, appears to be more effective. A different class of antidepressants, the monoamine oxidase inhibitors, have historically been plagued by questionable efficacy (although early studies used dosages now considered too low) and life-threatening adverse effects. They are still used only rarely, although newer agents of this class (RIMA), with a better side effect profile, have been developed.
In older patients TCAs and SSRIs are of the same efficacy. However, there are differences between TCA related antidepressants and classical TCAs in terms of side effect profiles and withdrawal when compared to SSRIs.
There is evidence a prominent side-effect of antidepressants, emotional blunting, is confused with a symptom of depression itself. The cited study, according to Professor Linda Gask was: ‘funded by a pharmaceutical company (Servier) and two of its authors are employees of that company’, which may bias the results. The study authors’ note: “emotional blunting is reported by nearly half of depressed patients on antidepressants and that it appears to be common to all monoaminergic antidepressants not only SSRIs”. Additionally, they note: “The OQuESA scores are highly correlated with the HAD depression score; emotional blunting cannot be described simply as a side-effect of antidepressant, but also as a symptom of depression…More emotional blunting is associated with a poorer quality of remission…”
Acetylcarnitine levels were lower in depressed patients than controls and in rats it causes rapid antidepressant effects through epigenetic mechanisms. A systematic review and meta-analysis of 12 randomised controlled trials found “supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects.”
A 2012 cross-sectional study found an association between zinc deficiency and depressive symptoms among women, but not men, and a 2013 meta-analysis of 17 observational studies found that blood zinc concentrations were lower in depressed subjects than in control subjects. A 2012 meta-analysis found that zinc supplementation as an adjunct to antidepressant drug treatment significantly lowered depressive symptom scores of depressed patients. The potential mechanisms underlying the association between low serum zinc and depression remain unclear, but may involve the regulation of neurotransmitter, endocrine and neurogenesis pathways. Zinc supplementation has been reported to improve symptoms of ADHD and depression. A 2013 review found that zinc supplementation may be an effective treatment in major depression.
Many studies have found an association between magnesium intake and depression. Magnesium was lower in serum of depressed patients than controls. One trial found magnesium chloride to be effective for depression in seniors with type 2 diabetes while another trial found magnesium citrate decreased depression in patients with fibromyalgia. One negative trial used magnesium oxide, which is poorly absorbed. A randomised, open-label study found that consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in depression, and that effects were observed within 2 weeks.
Physicians often add a medication with a different mode of action to bolster the effect of an antidepressant in cases of treatment resistance; a 2002 large community study of 244,859 depressed Veterans Administration patients found that 22% had received a second agent, most commonly a second antidepressant. Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. Addition of atypical antipsychotics when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit at the cost of more frequent and potentially serious side effects. There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function. Stephen M. Stahl, renowned academician in psychopharmacology, has stated resorting to a dynamic psychostimulant, in particular, d-amphetamine is the “classical augmentation strategy for treatment-refractory depression”. However, the use of stimulants in cases of treatment-resistant depression is relatively controversial.
Efficacy of Medication and Psychotherapy
Antidepressants are statistically superior to placebo but their overall effect is low-to-moderate. In that respect they often did not exceed the National Institute for Health and Clinical Excellence (NICE) criteria for a “clinically significant” effect. In particular, the effect size was very small for moderate depression but increased with severity, reaching “clinical significance” for very severe depression. These results were consistent with the earlier clinical studies in which only patients with severe depression benefited from either psychotherapy or treatment with an antidepressant, imipramine, more than from the placebo treatment. Despite obtaining similar results, the authors argued about their interpretation. One author concluded that there “seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit.” The other author agreed that “antidepressant ‘glass’ is far from full” but disagreed “that it is completely empty”. He pointed out that the first-line alternative to medication is psychotherapy, which does not have superior efficacy.
Antidepressants in general are as effective as psychotherapy for major depression, and this conclusion holds true for both severe and mild forms of MDD. In contrast, medication gives better results for dysthymia. The subgroup of SSRIs may be slightly more efficacious than psychotherapy. On the other hand, significantly more patients drop off from the antidepressant treatment than from psychotherapy, likely because of the side effects of antidepressants. Successful psychotherapy appears to prevent the recurrence of depression even after it has been terminated or replaced by occasional “booster” sessions. The same degree of prevention can be achieved by continuing antidepressant treatment.
Two studies suggest that the combination of psychotherapy and medication is the most effective way to treat depression in adolescents. Both TADS (Treatment of Adolescents with Depression Study) and TORDIA (Treatment of Resistant Depression in Adolescents) showed very similar results. TADS resulted in 71% of their teen subjects having “much” or “very much” improvement in mood over the 61% with medication alone and 43% with CBT alone. Similarly, TORDIA showed a 55% improvement with CBT and drugs versus a 41% with drug therapy alone. However, a more recent meta-analysis of 34 trials of 14 drugs used with children and adolescents found that only fluoxetine produced significant benefit compared to placebo, with a medium sized effect (standardize mean difference = .5).
The risk factors for treatment resistant depression are: the duration of the episode of depression, severity of the episode, if bipolar, lack of improvement in symptoms within the first couple of treatment weeks, anxious or avoidant and borderline comorbidity and old age. Treatment resistant depression is best handled with a combination of conventional antidepressant together with atypical antipsychotics. Another approach is to try different antidepressants. It is inconclusive which approach is superior. Treatment resistant depression can be misdiagnosed if subtherapeutic doses of antidepressants is the case, patient nonadherence, intolerable adverse effects or their thyroid disease or other conditions is misdiagnosed as depression.
Clinical and experimental studies have reported antidepressant activity of chromium particularly in atypical depression, characterised by increased appetite and carbohydrate craving.
Essential Fatty Acids
A 2015 Cochrane Collaboration review found insufficient evidence with which to determine if omega-3 fatty acid has any effect on depression. A 2016 review found that if trials with formulations containing mostly eicosapentaenoic acid (EPA) are separated from trials using formulations containing docosahexaenoic acid (DHA), it appeared that EPA may have an effect while DHA may not, but there was insufficient evidence to be sure.
The amino acid creatine, commonly used as a supplement to improve the performance of bodybuilders, has been studied for its potential antidepressant properties. A double-blinded, placebo-controlled trial focusing on women with major depressive disorder found that daily creatine supplementation adjunctive to escitalopram was more effective than escitalopram alone. Studies on mice have found that the antidepressant effects of creatine can be blocked by drugs that act against dopamine receptors, suggesting that the drug acts on dopamine pathways.
Dopamine Receptor Agonist
Some research suggests dopamine receptor agonist may be effective in treating depression, however studies are few and results are preliminary.
Inositol, an alcohol sugar found in fruits, beans grains and nuts may have antidepressant effects in high doses. Inositol may exert its effects by altering intracellular signalling.
Research on the antidepressant effects of ketamine infusions at subanaesthetic doses has consistently shown rapid (4 to 72 hours) responses from single doses, with substantial improvement in mood in the majority of patients and remission in some. However, these effects are often short-lived, and attempts to prolong the antidepressant effect with repeated doses and extended (“maintenance”) treatment have resulted in only modest success.
A systematic review and meta-analysis of 5 studies found that N-Acetylcysteine reduces depressive symptoms more than placebo and has good tolerability. N-Acetylecysteine may exert benefits as a precursor to the antioxidant glutathione, thus modulating glutamatergic, neurotropic, and inflammatory pathways.
St John’s Wort
A 2008 Cochrane Collaboration meta-analysis concluded that:
“The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.”
The United States National Centre for Complementary and Integrative Health advice is that “St. John’s wort may help some types of depression, similar to treatment with standard prescription antidepressants, but the evidence is not definitive.” and warns that “Combining St. John’s wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, a brain chemical targeted by antidepressants. St. John’s wort can also limit the effectiveness of many prescription medicines.”
A 2011 review reported Rhodiola rosea “is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects.” A 6 week double-blind, placebo-controlled, randomised study with 89 patients with mild to moderate depression found that R. rosea statistically significantly reduced depression symptoms, and no side effects were reported.
A 2013 meta-analysis found that saffron supplementation significantly reduced depression symptoms compared to placebo, and both saffron supplementation and the antidepressant groups were similarly effective in reducing depression symptoms. A 2015 meta-analysis supported the “efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior.” The antidepressant effect of saffron stigma extracts may be mediated via its components safranal and crocin: “crocin may act via the uptake inhibition of dopamine and norepinephrine, and safranal via serotonin.” Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.
S-Adenosyl methionine (SAMe) is available as a prescription antidepressant in Europe and an over-the-counter dietary supplement in the US. Evidence from 16 clinical trials with a small number of subjects, reviewed in 1994 and 1996 suggested it to be more effective than placebo and as effective as standard antidepressant medication for the treatment of major depression.
Tryptophan and 5-HTP
The amino acid tryptophan is converted into 5-hydroxytryptophan (5-HTP) which is subsequently converted into the neurotransmitter serotonin. Since serotonin deficiency has been recognized as a possible cause of depression, it has been suggested that consumption of tryptophan or 5-HTP may therefore improve depression symptoms by increasing the level of serotonin in the brain. 5-HTP and tryptophan are sold over the counter in North America, but requires a prescription in Europe. The use of 5-HTP instead of tryptophan bypasses the conversion of tryptophan into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin, and 5-HTP easily crosses the blood–brain barrier unlike tryptophan, which requires a transporter.
Small studies have been performed using 5-HTP and tryptophan as adjunctive therapy in addition to standard treatment for depression. While some studies had positive results, they were criticised for having methodological flaws, and a more recent study did not find sustained benefit from their use. The safety of these medications has not been well studied. Due to the lack of high quality studies, preliminary nature of studies showing effectiveness, the lack of adequate study on their safety, and reports of Eosinophilia-myalgia syndrome from contaminated tryptophan in 1989 and 1990, the use of tryptophan and 5-HTP is not highly recommended or thought to be clinically useful.
A variety of medical devices are in use or under consideration for treatment of depression including devices that offer electroconvulsive therapy, vagus nerve stimulation, repetitive transcranial magnetic stimulation, and cranial electrotherapy stimulation. The use of such devices in the United States requires approval by the US Food and Drug Administration (FDA) after field trials. In 2010 an FDA advisory panel considered the question of how such field trials should be managed. Factors considered were whether drugs had been effective, how many different drugs had been tried, and what tolerance for suicides should be in field trials.
Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in patients to provide relief from psychiatric illnesses. ECT is used with informed consent as a last line of intervention for major depressive disorder. Among the elderly, who often experience depression, the efficacy of ECT is difficult to determine due to the lack of trials comparing ECT to other treatments.
A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar. Follow-up treatment is still poorly studied, but about half of people who respond, relapse with twelve months.
Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anaesthesia. Immediately following treatment, the most common adverse effects are confusion and memory loss. ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.
A usual course of ECT involves multiple administrations, typically given two or three times per week until the patient is no longer suffering symptoms ECT is administered under anaesthetic with a muscle relaxant. Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some patients receive maintenance ECT.
ECT appears to work in the short term via an anticonvulsant effect mostly in the frontal lobes, and longer term via neurotrophic effects primarily in the medial temporal lobe.
Deep Brain Stimulation
The support for the use of deep brain stimulation in treatment-resistant depression comes from a handful of case studies, and this treatment is still in a very early investigational stage. In this technique electrodes are implanted in a specific region of the brain, which is then continuously stimulated. A March 2010 systematic review found that “about half the patients did show dramatic improvement” and that adverse events were “generally trivial” given the younger psychiatric patient population than with movements disorders. Deep brain stimulation is available on an experimental basis only in the United States; no systems are approved by the FDA for this use. It is available in Australia.
Repetitive Transcranial Magnetic Stimulation
Transcranial magnetic stimulation (TMS) or deep transcranial magnetic stimulation is a non-invasive method used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or “coil” is placed near the head of the person receiving the treatment. The coil produces small electric currents in the region of the brain just under the coil via electromagnetic induction. The coil is connected to a pulse generator, or stimulator, that delivers electric current to the coil.
TMS was approved by the FDA for treatment-resistant major depressive disorder in 2008 and as of 2014 clinical evidence supports this use. The American Psychiatric Association, the Canadian Network for Mood and Anxiety Disorders, and the Royal Australia and New Zealand College of Psychiatrists have endorsed rTMS for trMDD.
Vagus Nerve Stimulation
Vagus nerve stimulation (VNS) uses an implanted electrode and generator to deliver electrical pulses to the vagus nerve, one of the primary nerves emanating from the brain. It is an approved therapy for treatment-resistant depression in the EU and US and is sometimes used as an adjunct to existing antidepressant treatment. The support for this method comes mainly from open-label trials, which indicate that several months may be required to see a benefit. The only large double-blind trial conducted lasted only 10 weeks and yielded inconclusive results; VNS failed to show superiority over a sham treatment on the primary efficacy outcome, but the results were more favourable for one of the secondary outcomes. The authors concluded “This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.”
Cranial Electrotherapy Stimulation
A 2014 Cochrane review found insufficient evidence to determine whether or not Cranial electrotherapy stimulation with alternating current is safe and effective for treating depression.
Transcranial Direct Current Stimulation
A 2016 meta-analysis of transcranial direct current stimulation (tDCS) reported some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression, and that use of 2 mA current strength over 20 minutes per day over a short time span can be considered safe.
Bright Light Therapy
A meta-analysis of bright light therapy commissioned by the American Psychiatric Association found a significant reduction in depression symptom severity associated with bright light treatment. Benefit was found for both seasonal affective disorder and for non-seasonal depression, with effect sizes similar to those for conventional antidepressants. For non-seasonal depression, adding light therapy to the standard antidepressant treatment was not effective. A meta-analysis of light therapy for non-seasonal depression conducted by Cochrane Collaboration, studied a different set of trials, where light was used mostly in combination with antidepressants or wake therapy. A moderate statistically significant effect of light therapy was found, with response significantly better than control treatment in high-quality studies, in studies that applied morning light treatment, and with patients who respond to total or partial sleep deprivation. Both analyses noted poor quality of most studies and their small size, and urged caution in the interpretation of their results. The short 1-2 weeks duration of most trials makes it unclear whether the effect of light therapy could be sustained in the longer term.
The 2013 Cochrane Collaboration review on physical exercise for depression noted that, based upon limited evidence, it is moderately more effective than a control intervention and comparable to psychological or antidepressant drug therapies. Smaller effects were seen in more methodologically rigorous studies. Three subsequent 2014 systematic reviews that included the Cochrane review in their analysis concluded with similar findings: one indicated that physical exercise is effective as an adjunct treatment with antidepressant medication; the other two indicated that physical exercise has marked antidepressant effects and recommended the inclusion of physical activity as an adjunct treatment for mild-moderate depression and mental illness in general. These studies also found smaller effect sizes in more methodologically rigorous studies. All four systematic reviews called for more research in order to determine the efficacy or optimal exercise intensity, duration, and modality. The evidence for brain-derived neurotrophic factor (BDNF) in mediating some of the neurobiological effects of physical exercise was noted in one review which hypothesized that increased BDNF signalling is responsible for the antidepressant effect.
Mindfulness meditation programs may help improve symptoms of depression, but they are no better than active treatments such as medication, exercise, and other behavioural therapies.
A 2009 review found that 3 to 10 sessions of music therapy resulted in a noticeable improvement in depressive symptoms, with still greater improvement after 16 to 51 sessions.
Depression is sometimes associated with insomnia – (difficulty in falling asleep, early waking, or waking in the middle of the night). The combination of these two results, depression and insomnia, will only worsen the situation. Hence, good sleep hygiene is important to help break this vicious circle. It would include measures such as regular sleep routines, avoidance of stimulants such as caffeine and management of sleeping disorders such as sleep apnoea.
Quitting smoking cigarettes is associated with reduced depression and anxiety, with the effect “equal or larger than” those of antidepressant treatments.
Total/Partial Sleep Deprivation
Sleep deprivation (skipping a night’s sleep) has been found to improve symptoms of depression in 40-60% of patients. Partial sleep deprivation in the second half of the night may be as effective as an all night sleep deprivation session. Improvement may last for weeks, though the majority (50-80%) relapse after recovery sleep. Shifting or reduction of sleep time, light therapy, antidepressant drugs, and lithium have been found to potentially stabilise sleep deprivation treatment effects.
Shared care, when primary and specialty physicians have joint management of an individual’s health care, has been shown to alleviate depression outcomes.
The gut-brain axis is the biochemical signalling that takes place between the gastrointestinal tract (GI tract) and the central nervous system (CNS).
The term “gut-brain axis” is occasionally used to refer to the role of the gut flora in the interplay as well, whereas the term “microbiota–gut–brain (MGB or BGM) axis” explicitly includes the role of gut flora in the biochemical signalling events that take place between the GI tract and CNS.
Broadly defined, the gut-brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, including the hypothalamic-pituitary-adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, including the enteric nervous system and the vagus nerve, and the gut microbiota. The first of the brain-gut interactions shown, was the cephalic phase of digestion, in the release of gastric and pancreatic secretions in response to sensory signals, such as the smell and sight of food. This was first demonstrated by Pavlov.
Interest in the field was sparked by a 2004 study showing that germ-free (GF) mice showed an exaggerated HPA axis response to stress compared to non-GF laboratory mice.
As of October 2016, most of the work done on the role of gut flora in the gut-brain axis had been conducted in animals, or on characterising the various neuroactive compounds that gut flora can produce. Studies with humans – measuring variations in gut flora between people with various psychiatric and neurological conditions or when stressed, or measuring effects of various probiotics (dubbed “psychobiotics” in this context) – had generally been small and were just beginning to be generalised. Whether changes to gut flora are a result of disease, a cause of disease, or both in any number of possible feedback loops in the gut–brain axis, remained unclear.
The gut flora is the complex community of microorganisms that live in the digestive tracts of humans and other animals. The gut metagenome is the aggregate of all the genomes of gut microbiota. The gut is one niche that human microbiota inhabit.
In humans, the gut microbiota has the largest quantity of bacteria and the greatest number of species, compared to other areas of the body. In humans, the gut flora is established at one to two years after birth; by that time, the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms.
The relationship between gut flora and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship. Human gut microorganisms benefit the host by collecting the energy from the fermentation of undigested carbohydrates and the subsequent absorption of short-chain fatty acids (SCFAs), acetate, butyrate, and propionate. Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolising bile acids, sterols, and xenobiotics. The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ; dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.
The composition of human gut flora changes over time, when the diet changes, and as overall health changes.
Enteric Nervous System
The enteric nervous system is one of the main divisions of the nervous system and consists of a mesh-like system of neurons that governs the function of the gastrointestinal system; it has been described as a “second brain” for several reasons. The enteric nervous system can operate autonomously. It normally communicates with the central nervous system (CNS) through the parasympathetic (e.g. via the vagus nerve) and sympathetic (e.g. via the prevertebral ganglia) nervous systems. However, vertebrate studies show that when the vagus nerve is severed, the enteric nervous system continues to function.
In vertebrates, the enteric nervous system includes efferent neurons, afferent neurons, and interneurons, all of which make the enteric nervous system capable of carrying reflexes in the absence of CNS input. The sensory neurons report on mechanical and chemical conditions. Through intestinal muscles, the motor neurons control peristalsis and churning of intestinal contents. Other neurons control the secretion of enzymes. The enteric nervous system also makes use of more than 30 neurotransmitters, most of which are identical to the ones found in CNS, such as acetylcholine, dopamine, and serotonin. More than 90% of the body’s serotonin lies in the gut, as well as about 50% of the body’s dopamine; the dual function of these neurotransmitters is an active part of gut-brain research.
The first of the gut-brain interactions was shown to be between the sight and smell of food and the release of gastric secretions, known as the cephalic phase, or cephalic response of digestion.
The gut-brain axis, a bidirectional neurohumoral communication system, is important for maintaining homeostasis and is regulated through the central and enteric nervous systems and the neural, endocrine, immune, and metabolic pathways, and especially including the hypothalamic-pituitary-adrenal axis (HPA axis). That term has been expanded to include the role of the gut flora as part of the “microbiome-gut-brain axis”, a linkage of functions including the gut flora.
Interest in the field was sparked by a 2004 study (Nobuyuki Sudo and Yoichi Chida) showing that germ-free mice (genetically homogeneous laboratory mice, birthed and raised in an antiseptic environment) showed an exaggerated HPA axis response to stress, compared to non-GF laboratory mice.
The gut flora can produce a range of neuroactive molecules, such as acetylcholine, catecholamines, γ-aminobutyric acid, histamine, melatonin, and serotonin, which are essential for regulating peristalsis and sensation in the gut. Changes in the composition of the gut flora due to diet, drugs, or disease correlate with changes in levels of circulating cytokines, some of which can affect brain function. The gut flora also release molecules that can directly activate the vagus nerve, which transmits information about the state of the intestines to the brain.
Likewise, chronic or acutely stressful situations activate the hypothalamic-pituitary-adrenal axis, causing changes in the gut flora and intestinal epithelium, and possibly having systemic effects. Additionally, the cholinergic anti-inflammatory pathway, signalling through the vagus nerve, affects the gut epithelium and flora. Hunger and satiety are integrated in the brain, and the presence or absence of food in the gut and types of food present also affect the composition and activity of gut flora.
That said, most of the work that has been done on the role of gut flora in the gut-brain axis has been conducted in animals, including the highly artificial germ-free mice. As of 2016, studies with humans measuring changes to gut flora in response to stress, or measuring effects of various probiotics, have generally been small and cannot be generalised; whether changes to gut flora are a result of disease, a cause of disease, or both in any number of possible feedback loops in the gut-brain axis, remains unclear.
The history of ideas about a relationship between the gut and the mind dates from the nineteenth century. The concepts of dyspepsia and neurasthenia gastrica referred to the influence of the gut on human emotions and thoughts.
A unifying theory that tied gastrointestinal mechanisms to anxiety, depression, and skin conditions such as acne was proposed as early as 1930. In a paper in 1930, it was proposed that emotional states might alter normal intestinal flora which could lead to increased intestinal permeability and therefore contribute to systemic inflammation. Many aspects of this theory have been validated since then. Gut microbiota and oral probiotics have been found to influence systemic inflammation, oxidative stress, glycaemic control, tissue lipid content, and mood.
A 2016 systematic review of laboratory animal studies and preliminary human clinical trials using commercially available strains of probiotic bacteria found that certain species of the Bifidobacterium and Lactobacillus genera (i.e. B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei) had the most potential to be useful for certain central nervous system disorders.
Anxiety and Mood Disorders
As of 2018 work on the relationship between gut flora and anxiety disorders and mood disorders, as well as attempts to influence that relationship using probiotics or prebiotics (called “psychobiotics”), was at an early stage, with insufficient evidence to draw conclusions about a causal role for gut flora changes in these conditions, or about the efficacy of any probiotic or prebiotic treatment.
People with anxiety and mood disorders tend to have gastrointestinal problems; small studies have been conducted to compare the gut flora of people with major depressive disorder and healthy people, but those studies have had contradictory results.
Much interest was generated in the potential role of gut flora in anxiety disorders, and more generally in the role of gut flora in the gut-brain axis, by studies published in 2004 showing that germ-free mice have an exaggerated HPA axis response to stress caused by being restrained, which was reversed by colonising their gut with a Bifidobacterium species. Studies looking at maternal separation for rats shows neonatal stress leads to long-term changes in the gut microbiota such as its diversity and composition, which also led to stress and anxiety-like behaviour. Additionally, while much work had been done as of 2016 to characterise various neurotransmitters known to be involved in anxiety and mood disorders that gut flora can produce (for example, Escherichia, Bacillus, and Saccharomyces species can produce noradrenalin; Candida, Streptococcus, and Escherichia species can produce serotonin, etc.) the interrelationships and pathways by which the gut flora might affect anxiety in humans were unclear.
In one study, germ-free mice underwent faecal transplants with microbes from humans with or without major depressive disorder (MDD). Mice with microbes from humans with MDD displayed more behaviours associated with anxiety and depression than mice transplanted with microbes from humans without MDD. The taxonomic composition of microbiota between depressed patients and healthy patients, as well as between the respective mice, also differed. Germ-free mice in another study also displayed behaviours associated with anxiety and depression as compared to mice with normal microbiota, and had higher levels of corticosterone after exposure to behavioural tests. Using rodents in microbiome and mental health studies allows researchers to compare behaviour and microbial composition of rodents to humans, ideally to elucidate therapeutic application for mental disorders.
Additionally, there is a link between the gut microbiome, mood disorders and anxiety, and sleep. The microbial composition of the gut microbiome changes depending on the time of day, meaning that throughout the day, the gut is exposed to varying metabolites produced by the microbes active during that time. These time-dependent microbial changes are associated with differences in the transcription of circadian clock genes involved in circadian rhythm. One mouse study showed that altering clock gene transcription by disrupting circadian rhythm, such as through sleep deprivation, potentially has a direct effect on the composition of the gut microbiome. Another study found that mice that could not produce the CLOCK protein, made by a clock gene, were more likely to develop depression. Stress and sleep disturbances can lead to greater gut mucosal permeability via activation of the HPA axis. This in turn causes immune inflammatory responses that contribute to the development of illnesses that cause depression and anxiety.
Around 70% of people with autism also have gastrointestinal problems, and autism is often diagnosed at the time that the gut flora becomes established, indicating that there may be a connection between autism and gut flora. Some studies have found differences in the gut flora of children with autism compared with children without autism – most notably elevations in the amount of Clostridium in the stools of children with autism compared with the stools of the children without – but these results have not been consistently replicated. Many of the environmental factors thought to be relevant to the development of autism would also affect the gut flora, leaving open the question of whether specific developments in the gut flora drive the development of autism or whether those developments happen concurrently. As of 2016, studies with probiotics had only been conducted with animals; studies of other dietary changes to treat autism have been inconclusive.
As of 2015, one study had been conducted comparing the gut flora of people with Parkinson’s disease to healthy controls; in that study people with Parkinson’s had lower levels of Prevotellaceae and people with Parkinson’s who had higher levels of Enterobacteriaceae had more clinically severe symptoms; the authors of the study drew no conclusions about whether gut flora changes were driving the disease or vice versa.
Seasonal affective disorder (SAD) is a mood disorder subset in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year, most commonly in winter. Common symptoms include sleeping too much and having little to no energy, and overeating. The condition in the summer can include heightened anxiety.
In the Diagnostic and Statistical Manual of Mental Disorders DSM-IV and DSM-5, its status was changed. It is no longer classified as a unique mood disorder but is now a specifier, called “with seasonal pattern”, for recurrent major depressive disorder that occurs at a specific time of the year and fully remits otherwise. Although experts were initially sceptical, this condition is now recognised as a common disorder.
In the United States, the percentage of the population affected by SAD ranges from 1.4% of the population in Florida, to 9.9% in Alaska. SAD was formally described and named in 1984 by Norman E. Rosenthal and colleagues at the National Institute of Mental Health.
SAD was first systematically reported and named in the early 1980s by Norman E. Rosenthal, M.D., and his associates at the National Institute of Mental Health (NIMH). Rosenthal was initially motivated by his desire to discover the cause of his own experience of depression during the dark days of the northern US winter. He theorised that the reduction in available natural light during winter was the cause. Rosenthal and his colleagues then documented the phenomenon of SAD in a placebo-controlled study utilising light therapy. A paper based on this research was published in 1984. Although Rosenthal’s ideas were initially greeted with scepticism, SAD has become well recognised, and his 1993 book, Winter Blues has become the standard introduction to the subject.
Research on SAD in the United States began in 1979 when Herb Kern, a research engineer, had also noticed that he felt depressed during the winter months. Kern suspected that scarcer light in winter was the cause and discussed the idea with scientists at the NIMH who were working on bodily rhythms. They were intrigued, and responded by devising a lightbox to treat Kern’s depression. Kern felt much better within a few days of treatments, as did other patients treated in the same way.
Signs and Symptoms
SAD is a type of major depressive disorder (MDD), and sufferers may exhibit any of the associated symptoms, such as feelings of hopelessness and worthlessness, thoughts of suicide, loss of interest in activities, withdrawal from social interaction, sleep and appetite problems, difficulty with concentrating and making decisions, decreased libido, a lack of energy, or agitation. Symptoms of winter SAD often include oversleeping or difficulty waking up in the morning, nausea, and a tendency to overeat, often with a craving for carbohydrates, which leads to weight gain. SAD is typically associated with winter depression, but springtime lethargy or other seasonal mood patterns are not uncommon. Although each individual case is different, in contrast to winter SAD, people who experience spring and summer depression may be more likely to show symptoms such as insomnia, decreased appetite and weight loss, and agitation or anxiety.
With seasonal pattern is a specifier for bipolar and related disorders, including bipolar I disorder and bipolar II disorder. Most people with SAD experience major depressive disorder, but as many as 20% may have a bipolar disorder. It is important to discriminate between diagnoses because there are important treatment differences. In these cases, people who have the With seasonal pattern specifier may experience a depressive episode either due to MDD or as part of bipolar disorder during the winter and remit in the summer. Around 25% of patients with bipolar disorder may present with a depressive seasonal pattern, which is associated with bipolar II disorder, rapid cycling, eating disorders, and more depressive episodes. Differences in biological sex display distinct clinical characteristics associated to seasonal pattern: males present with more Bipolar II disorder and a higher number of depressive episodes, and females with rapid cycling and eating disorders.
In many species, activity is diminished during the winter months in response to the reduction in available food, the reduction of sunlight (especially for diurnal animals) and the difficulties of surviving in cold weather. Hibernation is an extreme example, but even species that do not hibernate often exhibit changes in behaviour during the winter. Presumably, food was scarce during most of human prehistory, and a tendency toward low mood during the winter months would have been adaptive by reducing the need for calorie intake. The preponderance of women with SAD suggests that the response may also somehow regulate reproduction.
Various proximate causes have been proposed. One possibility is that SAD is related to a lack of serotonin, and serotonin polymorphisms could play a role in SAD, although this has been disputed. Mice incapable of turning serotonin into N-acetylserotonin (by serotonin N-acetyltransferase) appear to express “depression-like” behaviour, and antidepressants such as fluoxetine increase the amount of the enzyme serotonin N-acetyltransferase, resulting in an antidepressant-like effect. Another theory is that the cause may be related to melatonin which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the retinohypothalamic tract and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light.
One study looked at whether some people could be predisposed to SAD based on personality traits. Correlations between certain personality traits, higher levels of neuroticism, agreeableness, openness, and an avoidance-oriented coping style, appeared to be common in those with SAD.
Seasonal mood variations are believed to be related to light. An argument for this view is the effectiveness of bright-light therapy. SAD is measurably present at latitudes in the Arctic region, such as northern Finland (64°00′N), where the rate of SAD is 9.5%. Cloud cover may contribute to the negative effects of SAD. There is evidence that many patients with SAD have a delay in their circadian rhythm, and that bright light treatment corrects these delays which may be responsible for the improvement in patients.
The symptoms of it mimic those of dysthymia or even major depressive disorder. There is also potential risk of suicide in some patients experiencing SAD. One study reports 6-35% of sufferers required hospitalization during one period of illness. At times, patients may not feel depressed, but rather lack energy to perform everyday activities.
Subsyndromal Seasonal Affective Disorder is a milder form of SAD experienced by an estimated 14.3% (vs. 6.1% SAD) of the US population. The blue feeling experienced by both SAD and SSAD sufferers can usually be dampened or extinguished by exercise and increased outdoor activity, particularly on sunny days, resulting in increased solar exposure. Connections between human mood, as well as energy levels, and the seasons are well documented, even in healthy individuals.
According to the American Psychiatric Association DSM-IV criteria, Seasonal Affective Disorder is not regarded as a separate disorder. It is called a “course specifier” and may be applied as an added description to the pattern of major depressive episodes in patients with major depressive disorder or patients with bipolar disorder.
The “Seasonal Pattern Specifier” must meet four criteria: depressive episodes at a particular time of the year; remissions or mania/hypomania at a characteristic time of year; these patterns must have lasted two years with no non-seasonal major depressive episodes during that same period; and these seasonal depressive episodes outnumber other depressive episodes throughout the patient’s lifetime. The Mayo Clinic describes three types of SAD, each with its own set of symptoms.
Treatments for classic (winter-based) seasonal affective disorder include light therapy, medication, ionized-air administration, cognitive-behavioural therapy (CBT) and carefully timed supplementation of the hormone melatonin.
Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a lightbox which emits far more lumens than a customary incandescent lamp. Bright white “full spectrum” light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred.
Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30-60 cm, in front of the box with her/his eyes open but not staring at the light source for 30-60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient and as many as 19% stop use because of this.
Dawn simulation has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Most studies have found it effective without use year round but rather as a seasonal treatment lasting for several weeks until frequent light exposure is naturally obtained.
Light therapy can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that don’t block the ultraviolet range should be avoided due to the threat of skin cancer.
The evidence base for light therapy as a preventive treatment for seasonal affective disorder is limited. The decision to use light therapy to treat people with a history of winter depression before depressive symptoms begin should be based on a persons preference of treatment.
SSRI (selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine, sertraline, or paroxetine. Both fluoxetine and light therapy are 67% effective in treating SAD according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in four people, but has not been compared directly to other preventive options in trials.
Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression.
Another explanation is that vitamin D levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese nor among elderly British women.
Depending upon the patient, one treatment (e.g. lightbox) may be used in conjunction with another (e.g. medication).
Negative air ionisation, which involves releasing charged particles into the sleep environment, has been found effective with a 47.9% improvement if the negative ions are in sufficient density (quantity).
Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day along with the same amount of time underneath the UV light were seen to make quick recovery.
Of all the psychological therapies aimed at the prevention of SAD, cognitive-behaviour therapy, typically involving thought records, activity schedules and a positive data log, has been the subject of the most empirical work, however, evidence for CBT or any of the psychological therapies aimed at preventing SAD remains inconclusive.
Winter depression is a common slump in the mood of some inhabitants of most of the Nordic countries. It was first described by the 6th century Goth scholar Jordanes in his Getica wherein he described the inhabitants of Scandza (Scandinavia). Iceland, however, seems to be an exception. A study of more than 2000 people there found the prevalence of seasonal affective disorder and seasonal changes in anxiety and depression to be unexpectedly low in both sexes. The study’s authors suggested that propensity for SAD may differ due to some genetic factor within the Icelandic population. A study of Canadians of wholly Icelandic descent also showed low levels of SAD. It has more recently been suggested that this may be attributed to the large amount of fish traditionally eaten by Icelandic people, in 2007 about 90 kilograms per person per year as opposed to about 24 kg in the US and Canada, rather than to genetic predisposition; a similar anomaly is noted in Japan, where annual fish consumption in recent years averages about 60 kg per capita. Fish are high in vitamin D. Fish also contain docosahexaenoic acid (DHA), which help with a variety of neurological dysfunctions.
In the US, a diagnosis of SAD was first proposed by Norman E. Rosenthal, M.D. in 1984. Rosenthal wondered why he became sluggish during the winter after moving from sunny South Africa to (cloudy in winter) New York. He started experimenting increasing exposure to artificial light, and found this made a difference. In Alaska it has been established that there is a SAD rate of 8.9%, and an even greater rate of 24.9% for subsyndromal SAD.
Around 20% of Irish people are affected by SAD, according to a survey conducted in 2007. The survey also shows women are more likely to be affected by SAD than men. An estimated 3% of the population in the Netherlands suffer from winter SAD.
Beating OCD and Anxiety – 75 Tried and Tested Strategies for Sufferers and their Supporters.
Author(s): Helena Tarrant.
Edition: First (1st).
Publisher: Cherish Editions.
Type(s): Paperback and Kindle.
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Mood disorder, also known as mood affective disorders, is a group of conditions where a disturbance in the person’s mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD).
Mood disorders fall into the basic groups of elevated mood, such as mania or hypomania; depressed mood, of which the best-known and most researched is major depressive disorder (MDD) (commonly called clinical depression, unipolar depression, or major depression); and moods which cycle between mania and depression, known as bipolar disorder (BD) (formerly known as manic depression). There are several sub-types of depressive disorders or psychiatric syndromes featuring less severe symptoms such as dysthymic disorder (similar to but milder than MDD) and cyclothymic disorder (similar to but milder than BD). Mood disorders may also be substance induced or occur in response to a medical condition.
English psychiatrist Henry Maudsley proposed an overarching category of affective disorder. The term was then replaced by mood-disorder, as the latter term refers to the underlying or longitudinal emotional state, whereas the former refers to the external expression observed by others.
According to a substantial amount of epidemiology studies conducted, women are twice as likely to develop certain mood disorders, such as major depression. Although there is an equal number of men and women diagnosed with bipolar II disorder, women have a slightly higher frequency of the disorder.
The prevalence of depressive symptoms has increased over the years with recent generations reporting a 6% increase in symptoms of depression compared to individuals from older generations.
In 2011, mood disorders were the most common reason for hospitalization among children aged 1-17 years in the United States, with approximately 112,000 stays. Mood disorders were top principal diagnosis for Medicaid super-utilisers in the United States in 2012. Further, a study of 18 States found that mood disorders accounted for the highest number of hospital readmissions among Medicaid patients and the uninsured, with 41,600 Medicaid patients and 12,200 uninsured patients being readmitted within 30 days of their index stay – a readmission rate of 19.8 per 100 admissions and 12.7 per 100 admissions, respectively. In 2012, mood and other behavioural health disorders were the most common diagnoses for Medicaid-covered and uninsured hospital stays in the United States (6.1% of Medicaid stays and 5.2% of uninsured stays).
A study conducted in 1988 to 1994 amongst young American adults involved a selection of demographic and health characteristics. A population-based sample of 8,602 men and women ages 17-39 years participated. Lifetime prevalence were estimated based on six mood measures:
Major depressive episode (MDE) 8.6%.
Major depressive disorder with severity (MDE-s) 7.7%.
MDE-s with dysthymia 3.4%.
Any bipolar disorder 1.6%.
Any mood disorder 11.5%.
Major depressive disorder (MDD):
Commonly called major depression, unipolar depression, or clinical depression, wherein a person has one or more major depressive episodes.
After a single episode, Major Depressive Disorder (single episode) would be diagnosed.
After more than one episode, the diagnosis becomes Major Depressive Disorder (Recurrent).
Depression without periods of mania is sometimes referred to as unipolar depression because the mood remains at the bottom “pole” and does not climb to the higher, manic “pole” as in bipolar disorder.
Individuals with a major depressive episode or major depressive disorder are at increased risk for suicide.
Seeking help and treatment from a health professional dramatically reduces the individual’s risk for suicide.
Studies have demonstrated that asking if a depressed friend or family member has thought of committing suicide is an effective way of identifying those at risk, and it does not “plant” the idea or increase an individual’s risk for suicide in any way.
Epidemiological studies carried out in Europe suggest that, at this moment, roughly 8.5% of the world’s population have a depressive disorder. No age group seems to be exempt from depression, and studies have found that depression appears in infants as young as 6 months old who have been separated from their mothers.
Depressive disorder is frequent in primary care and general hospital practice but is often undetected.
Unrecognised depressive disorder may slow recovery and worsen prognosis in physical illness, therefore it is important that all doctors be able to recognise the condition, treat the less severe cases, and identify those requiring specialist care.
Diagnosticians recognise several subtypes or course specifiers:
Atypical depression (AD):
This is characterised by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (“comfort eating”), excessive sleep or somnolence (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.
Difficulties in measuring this subtype have led to questions of its validity and prevalence.
This is characterised by a loss of pleasure (anhedonia) in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.
Psychotic major depression (PMD):
Or simply psychotic depression, is the term for a major depressive episode, in particular of melancholic nature, wherein the patient experiences psychotic symptoms such as delusions or, less commonly, hallucinations.
These are most commonly mood-congruent (content coincident with depressive themes).
This is a rare and severe form of major depression involving disturbances of motor behaviour and other symptoms.
Here, the person is mute and almost stuporose, and either is immobile or exhibits purposeless or even bizarre movements.
Catatonic symptoms can also occur in schizophrenia or a manic episode, or can be due to neuroleptic malignant syndrome.
Postpartum depression (PPD)
This is listed as a course specifier in DSM-IV-TR; it refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth.
Postpartum depression, which affects 10-15% of women, typically sets in within three months of labour, and lasts as long as three months.
It is quite common for women to experience a short-term feeling of tiredness and sadness in the first few weeks after giving birth; however, postpartum depression is different because it can cause significant hardship and impaired functioning at home, work, or school as well as, possibly, difficulty in relationships with family members, spouses, or friends, or even problems bonding with the newborn.
In the treatment of postpartum major depressive disorders and other unipolar depressions in women who are breastfeeding, nortriptyline, paroxetine (Paxil), and sertraline (Zoloft) are in general considered to be the preferred medications.
Women with personal or family histories of mood disorders are at particularly high risk of developing postpartum depression.
Premenstrual dysphoric disorder (PMDD):
This is a severe and disabling form of premenstrual syndrome affecting 3-8% of menstruating women.
The disorder consists of a “cluster of affective, behavioural and somatic symptoms” that recur monthly during the luteal phase of the menstrual cycle.
PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013.
The exact pathogenesis of the disorder is still unclear and is an active research topic. Treatment of PMDD relies largely on antidepressants that modulate serotonin levels in the brain via serotonin reuptake inhibitors as well as ovulation suppression using contraception.
Seasonal affective disorder (SAD):
Also known as “winter depression” or “winter blues”, is a specifier.
Some people have a seasonal pattern, with depressive episodes coming on in the autumn or winter, and resolving in spring.
The diagnosis is made if at least two episodes have occurred in colder months with none at other times over a two-year period or longer.
It is commonly hypothesised that people who live at higher latitudes tend to have less sunlight exposure in the winter and therefore experience higher rates of SAD, but the epidemiological support for this proposition is not strong (and latitude is not the only determinant of the amount of sunlight reaching the eyes in winter).
It is said that this disorder can be treated by light therapy.
SAD is also more prevalent in people who are younger and typically affects more females than males.
This is a condition related to unipolar depression, where the same physical and cognitive problems are evident, but they are not as severe and tend to last longer (usually at least 2 years).
Can be defined as a fairly depressed mood (dysthymia) that lasts for at least two years and is punctuated by periods of major depression.
Depressive Disorder Not Otherwise Specified (DD-NOS):
This is designated by the code 311 for depressive disorders that are impairing but do not fit any of the officially specified diagnoses.
According to the DSM-IV, DD-NOS encompasses “any depressive disorder that does not meet the criteria for a specific disorder.”
It includes the research diagnoses of recurrent brief depression, and minor depressive disorder listed below.
Depressive personality disorder (DPD)
This is a controversial psychiatric diagnosis that denotes a personality disorder with depressive features.
Originally included in the DSM-II, depressive personality disorder was removed from the DSM-III and DSM-III-R.
Recently, it has been reconsidered for reinstatement as a diagnosis. Depressive personality disorder is currently described in Appendix B in the DSM-IV-TR as worthy of further study.
Recurrent brief depression (RBD):
Distinguished from major depressive disorder primarily by differences in duration.
Individuals with RBD have depressive episodes about once per month, with individual episodes lasting less than two weeks and typically less than 2-3 days.
Diagnosis of RBD requires that the episodes occur over the span of at least one year and, in female patients, independently of the menstrual cycle.
Individuals with clinical depression can develop RBD, and vice versa, and both illnesses have similar risks.
Minor depressive disorder:
Or simply minor depression, which refers to a depression that does not meet full criteria for major depression but in which at least two symptoms are present for two weeks.
Bipolar disorder (BD) (also called “manic depression” or “manic-depressive disorder”), an unstable emotional condition characterised by cycles of abnormal, persistent high mood (mania) and low mood (depression), which was formerly known as “manic depression” (and in some cases rapid cycling, mixed states, and psychotic symptoms). Subtypes include:
This is distinguished by the presence or history of one or more manic episodes or mixed episodes with or without major depressive episodes.
A depressive episode is not required for the diagnosis of Bipolar I Disorder, but depressive episodes are usually part of the course of the illness.
Bipolar II :
Consisting of recurrent intermittent hypomanic and depressive episodes or mixed episodes.
This is a form of bipolar disorder, consisting of recurrent hypomanic and dysthymic episodes, but no full manic episodes or full major depressive episodes.
Bipolar disorder not otherwise specified (BD-NOS):
Sometimes called “sub-threshold” bipolar, indicates that the patient has some symptoms in the bipolar spectrum (e.g. manic and depressive symptoms) but does not fully qualify for any of the three formal bipolar DSM-IV diagnoses mentioned above.
It is estimated that roughly 1% of the adult population has bipolar I, a further 1% has bipolar II or cyclothymia, and somewhere between 2% and 5% percent have “sub-threshold” forms of bipolar disorder. Furthermore, the possibility of getting bipolar disorder when one parent is diagnosed with it is 15-30%. Risk, when both parents have it, is 50-75%. Also, while with bipolar siblings the risk is 15-25%, with identical twins it is about 70%.
A minority of people with bipolar disorder have high creativity, artistry or a particular gifted talent. Before the mania phase becomes too extreme, its energy, ambition, enthusiasm and grandiosity often bring people with this type of mood disorder life’s masterpieces.
A mood disorder can be classified as substance-induced if its aetiology can be traced to the direct physiologic effects of a psychoactive drug or other chemical substance, or if the development of the mood disorder occurred contemporaneously with substance intoxication or withdrawal. Also, an individual may have a mood disorder coexisting with a substance abuse disorder. Substance-induced mood disorders can have features of a manic, hypomanic, mixed, or depressive episode. Most substances can induce a variety of mood disorders. For example, stimulants such as amphetamine, methamphetamine, and cocaine can cause manic, hypomanic, mixed, and depressive episodes.
High rates of major depressive disorder occur in heavy drinkers and those with alcoholism. Controversy has previously surrounded whether those who abused alcohol and developed depression were self-medicating their pre-existing depression. But recent research has concluded that, while this may be true in some cases, alcohol misuse directly causes the development of depression in a significant number of heavy drinkers. Participants studied were also assessed during stressful events in their lives and measured on a Feeling Bad Scale. Likewise, they were also assessed on their affiliation with deviant peers, unemployment, and their partner’s substance use and criminal offending. High rates of suicide also occur in those who have alcohol-related problems. It is usually possible to differentiate between alcohol-related depression and depression that is not related to alcohol intake by taking a careful history of the patient. Depression and other mental health problems associated with alcohol misuse may be due to distortion of brain chemistry, as they tend to improve on their own after a period of abstinence.
Benzodiazepines, such as alprazolam, clonazepam, lorazepam and diazepam, can cause both depression and mania.
Benzodiazepines are a class of medication commonly used to treat anxiety, panic attacks and insomnia, and are also commonly misused and abused. Those with anxiety, panic and sleep problems commonly have negative emotions and thoughts, depression, suicidal ideations, and often have comorbid depressive disorders. While the anxiolytic and hypnotic effects of benzodiazepines disappear as tolerance develops, depression and impulsivity with high suicidal risk commonly persist. These symptoms are “often interpreted as an exacerbation or as a natural evolution of previous disorders and the chronic use of sedatives is overlooked”. Benzodiazepines do not prevent the development of depression, can exacerbate pre-existing depression, can cause depression in those with no history of it, and can lead to suicide attempts. Risk factors for attempted and completed suicide while using benzodiazepines include high dose prescriptions (even in those not misusing the medications), benzodiazepine intoxication, and underlying depression.
The long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and are also implicated in depression. As with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for the increased depression. Additionally, benzodiazepines can indirectly worsen mood by worsening sleep (i.e. benzodiazepine-induced sleep disorder). Like alcohol, benzodiazepines can put people to sleep but, while asleep, they disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep sleep (the most restorative part of sleep for both energy and mood). Just as some antidepressants can cause or worsen anxiety in some patients due to being activating, benzodiazepines can cause or worsen depression due to being a central nervous system depressant – worsening thinking, concentration and problem solving (i.e. benzodiazepine-induced neurocognitive disorder). However, unlike antidepressants, in which the activating effects usually improve with continued treatment, benzodiazepine-induced depression is unlikely to improve until after stopping the medication.
In a long-term follow-up study of patients dependent on benzodiazepines, it was found that 10 people (20%) had taken drug overdoses while on chronic benzodiazepine medication despite only two people ever having had any pre-existing depressive disorder. A year after a gradual withdrawal programme, no patients had taken any further overdoses.
Just as with intoxication and chronic use, benzodiazepine withdrawal can also cause depression. While benzodiazepine-induced depressive disorder may be exacerbated immediately after discontinuation of benzodiazepines, evidence suggests that mood significantly improves after the acute withdrawal period to levels better than during use. Depression resulting from withdrawal from benzodiazepines usually subsides after a few months but in some cases may persist for 6-12 months.
Due to Another Medical Condition
“Mood disorder due to a general medical condition” is used to describe manic or depressive episodes which occur secondary to a medical condition. There are many medical conditions that can trigger mood episodes, including neurological disorders (e.g. dementias), metabolic disorders (e.g. electrolyte disturbances), gastrointestinal diseases (e.g. cirrhosis), endocrine disease (e.g. thyroid abnormalities), cardiovascular disease (e.g. heart attack), pulmonary disease (e.g. chronic obstructive pulmonary disease), cancer, and autoimmune diseases (e.g. multiple sclerosis).
Not Otherwise Specified
Mood disorder not otherwise specified (MD-NOS) is a mood disorder that is impairing but does not fit in with any of the other officially specified diagnoses. In the DSM-IV MD-NOS is described as “any mood disorder that does not meet the criteria for a specific disorder.” MD-NOS is not used as a clinical description but as a statistical concept for filing purposes.
Most cases of MD-NOS represent hybrids between mood and anxiety disorders, such as mixed anxiety-depressive disorder or atypical depression. An example of an instance of MD-NOS is being in minor depression frequently during various intervals, such as once every month or once in three days. There is a risk for MD-NOS not to get noticed, and for that reason not to get treated.
Meta-analyses show that high scores on the personality domain neuroticism are a strong predictor for the development of mood disorders. A number of authors have also suggested that mood disorders are an evolutionary adaptation. A low or depressed mood can increase an individual’s ability to cope with situations in which the effort to pursue a major goal could result in danger, loss, or wasted effort. In such situations, low motivation may give an advantage by inhibiting certain actions. This theory helps to explain why negative life incidents precede depression in around 80% of cases, and why they so often strike people during their peak reproductive years. These characteristics would be difficult to understand if depression were a dysfunction.
A depressed mood is a predictable response to certain types of life occurrences, such as loss of status, divorce, or death of a child or spouse. These are events that signal a loss of reproductive ability or potential, or that did so in humans’ ancestral environment. A depressed mood can be seen as an adaptive response, in the sense that it causes an individual to turn away from the earlier (and reproductively unsuccessful) modes of behaviour.
A depressed mood is common during illnesses, such as influenza. It has been argued that this is an evolved mechanism that assists the individual in recovering by limiting his/her physical activity. The occurrence of low-level depression during the winter months, or seasonal affective disorder, may have been adaptive in the past, by limiting physical activity at times when food was scarce. It is argued that humans have retained the instinct to experience low mood during the winter months, even if the availability of food is no longer determined by the weather.
Much of what is known about the genetic influence of clinical depression is based upon research that has been done with identical twins. Identical twins have exactly the same genetic code. It has been found that when one identical twin becomes depressed the other will also develop clinical depression approximately 76% of the time. When identical twins are raised apart from each other, they will both become depressed about 67% of the time. Because both twins become depressed at such a high rate, the implication is that there is a strong genetic influence. If it happened that when one twin becomes clinically depressed the other always develops depression, then clinical depression would likely be entirely genetic.
Bipolar disorder is also considered a mood disorder and it is hypothesized that it might be caused by mitochondrial dysfunction.
Mood disorders, specifically stress-related mood disorders such as anxiety and depression, have been shown to have differing rates of diagnosis based on sex. In the United States, women are two times more likely than men to be diagnosed with a stress-related mood disorder. Underlying these sex differences, studies have shown a dysregulation of stress-responsive neuroendocrine function causing an increase in the likelihood of developing these affective disorders. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis could provide potential insight into how these sex differences arise. Neuropeptide corticotropin-releasing factor (CRF) is released from the paraventricular nucleus (PVN) of the hypothalamus, stimulating adrenocorticotropic hormone (ACTH) release into the blood stream. From here ACTH triggers the release of glucocorticoids such as cortisol from the adrenal cortex. Cortisol, known as the main stress hormone, creates a negative feedback loop back to the hypothalamus to deactivate the stress response. When a constant stressor is present, the HPA axis remains overactivated and cortisol is constantly produced. This chronic stress is associated with sustained CRF release, resulting in the increased production of anxiety- and depressive-like behaviours and serving as a potential mechanism for differences in prevalence between men and women.
The DSM-5, released in May 2013, separates the mood disorder chapter from the DSM-TR-IV into two sections: Depressive and related disorders and bipolar and related disorders. Bipolar disorders falls in between depressive disorders and schizophrenia spectrum and related disorders “in recognition of their place as a bridge between the two diagnostic classes in terms of symptomatology, family history and genetics” (Ref. 1, p 123). Bipolar disorders underwent a few changes in the DSM-5, most notably the addition of more specific symptomology related to hypomanic and mixed manic states. Depressive disorders underwent the most changes, the addition of three new disorders: disruptive mood dysregulation disorder, persistent depressive disorder (previously dysthymia), and premenstrual dysphoric disorder (previously in appendix B, the section for disorders needing further research). Disruptive mood dysregulation disorder is meant as a diagnosis for children and adolescents who would normally be diagnosed with bipolar disorder as a way to limit the bipolar diagnosis in this age cohort. Major depressive disorder (MDD) also underwent a notable change, in that the bereavement clause has been removed. Those previously exempt from a diagnosis of MDD due to bereavement are now candidates for the MDD diagnosis.
There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants; a combination of antidepressants and cognitive behavioural therapy has shown to be more effective than one treatment alone. Bipolar disorder medications can consist of antipsychotics, mood stabilisers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options. In determining treatment, there are many types of depression scales that are used.
One of the depression scales is a self-report scale called Beck Depression Inventory (BDI).
Another scale is the Hamilton Depression Rating Scale (HAMD).
HAMD is a clinical rating scale in which the patient is rated based on clinician observation.
The Centre for Epidemiologic Studies Depression Scale (CES-D) is a scale for depression symptoms that applies to the general population.
This scale is typically used in research and not for self-reports.
The PHQ-9 which stands for Patient-Health Questionnaire-9 questions, is a self-report as well.
Finally, the Mood Disorder Questionnaire (MDQ) evaluates bipolar disorder.
Kay Redfield Jamison and others have explored the possible links between mood disorders – especially bipolar disorder – and creativity. It has been proposed that a “ruminating personality type may contribute to both [mood disorders] and art.”
Jane Collingwood notes an Oregon State University study that:
“…looked at the occupational status of a large group of typical patients and found that ‘those with bipolar illness appear to be disproportionately concentrated in the most creative occupational category.’ They also found that the likelihood of ‘engaging in creative activities on the job’ is significantly higher for bipolar than nonbipolar workers”.
In Liz Paterek’s article “Bipolar Disorder and the Creative Mind” she wrote:
“Memory and creativity are related to mania. Clinical studies have shown that those in a manic state will rhyme, find synonyms, and use alliteration more than controls. This mental fluidity could contribute to an increase in creativity. Moreover, mania creates increases in productivity and energy. Those in a manic state are more emotionally sensitive and show less inhibition about attitudes, which could create greater expression. Studies performed at Harvard looked into the amount of original thinking in solving creative tasks. Bipolar individuals, whose disorder was not severe, tended to show greater degrees of creativity.”
The relationship between depression and creativity appears to be especially strong among poets.
Depression, one of the most commonly diagnosed psychiatric disorders, is being diagnosed in increasing numbers in various segments of the population worldwide. For example, depression in the United States (US) alone affects 17.6 million Americans each year or 1 in 6 people. Depressed patients are at increased risk of type 2 diabetes, cardiovascular disease and suicide. Within the next twenty years depression is expected to become the second leading cause of disability worldwide and the leading cause in high-income nations, including the US. In approximately 75% of completed suicides, the individuals had seen a physician within the prior year before their death, 45-66% within the prior month. About a third of those who completed suicide had contact with mental health services in the prior year, a fifth within the preceding month.
There are many psychiatric and medical conditions that may mimic some or all of the symptoms of depression or may occur comorbid to it. A disorder either psychiatric or medical that shares symptoms and characteristics of another disorder, and may be the true cause of the presenting symptoms is known as a differential diagnosis.
Many psychiatric disorders such as depression are diagnosed by allied health professionals with little or no medical training, and are made on the basis of presenting symptoms without proper consideration of the underlying cause, adequate screening of differential diagnoses is often not conducted. According to one study, non-medical mental health care providers may be at increased risk of not recognising masked medical illnesses in their patients.
Misdiagnosis or missed diagnoses may lead to lack of treatment or ineffective and potentially harmful treatment which may worsen the underlying causative disorder. A conservative estimate is that 10% of all psychological symptoms may be due to medical reasons, with the results of one study suggesting that about half of individuals with a serious mental illness have general medical conditions that are largely undiagnosed and untreated and may cause or exacerbate psychiatric symptoms.
In a case of misdiagnosed depression recounted in Newsweek, a writer received treatment for depression for years; during the last 10 years of her depression the symptoms worsened, resulting in multiple suicide attempts and psychiatric hospitalisations. When an MRI finally was performed, it showed the presence of a tumour. However, she was told by a neurologist that it was benign. After a worsening of symptoms, and upon the second opinion of another neurologist, the tumour was removed. After the surgery, she no longer suffered from depressive symptoms.
This is an autoimmune disorder in which the body is unable to digest gluten which is found in various food grains, most notably wheat, and also rye and barley.
Current research has shown its neuropsychiatric symptoms may manifest without the gastrointestinal symptoms.
However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology.
Systemic lupus erythematosus (SLE), is a chronic autoimmune connective tissue disease that can affect any part of the body.
Lupus can cause or worsen depression.
This is a bacterial infection caused by Borrelia burgdorferi, a spirochete bacterium transmitted by the Deer tick (Ixodes scapularis).
Lyme disease is one of a group of diseases which have earned the name the “great imitator” for their propensity to mimic the symptoms of a wide variety of medical and neuropsychiatric disorders.
Lyme disease is an underdiagnosed illness, partially as a result of the complexity and unreliability of serologic testing.
Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.
The prevalence of which is on the rise, is another of the “great imitators”, which if left untreated can progress to neurosyphilis and affect the brain, can present with solely neuropsychiatric symptoms.
This case emphasises that neurosyphilis still has to be considered in the differential diagnosis within the context of psychiatric conditions and diseases.
Owing to current epidemiological data and difficulties in diagnosing syphilis, routine screening tests in the psychiatric field are necessary.
This is an infection of the brain or spinal cord caused by the larval stage of the pork tapeworm, Taenia solium.
NCC is the most common helminthic (parasitic worm) infestation of the central nervous system worldwide. Humans develop cysticercosis when they ingest eggs of the pork tapeworm via contact with contaminated fecal matter or eating infected vegetables or undercooked pork.
While cysticercosis is endemic in Latin America, it is an emerging disease with increased prevalence in the United States.
The rate of depression in those with neurocysticercosis is higher than in the general population.
This is an infection caused by Toxoplasma gondii an intracellular protozoan parasite. Humans can be infected in 3 different ways:
Ingestion of tissue cysts;
Ingestion of oocysts; or
In utero infection with tachyzoites.
One of the prime methods for transmission to humans is contact with the faeces of the host species, the domesticated cat.
Toxoplasma gondii infects approximately 30% of the world’s human population, but causes overt clinical symptoms in only a small segment of those infected.
Exposure to Toxoplasma gondii (seropositivity) without developing Toxoplasmosis has been proven to alter various characteristics of human behaviour as well as being a causative factor in some cases of depression, in addition, studies have linked seropositivity with an increased rate of suicide
West Nile virus (WNV):
This can cause encephalitis has been reported to be a causal factor in developing depression in 31% of those infected in a study conducted in Houston, Texas and reported to the Centre for Disease Control (CDC).
The primary vectors for disease transmission to humans are various species of mosquito.
WNV which is endemic to Southern Europe, Africa the Middle East and Asia was first identified in the United States in 1999.
Between 1999 and 2006, 20,000 cases of confirmed symptomatic WNV were reported in the US, with estimates of up to 1 million being infected.
WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future.
This is a decrease in normal number of red blood cells (RBCs) or less than the normal quantity of haemoglobin in the blood.
Depressive symptoms are associated with anaemia in a general population of older persons living in the community.
Chronic Fatigue Syndrome
Between 1 and 4 million Americans are believed to have chronic fatigue syndrome (CFS), yet only 50% have consulted a physician for symptoms of CFS. In addition individuals with CFS symptoms often have an undiagnosed medical or psychiatric disorder such as diabetes, thyroid disease or substance abuse. CFS, at one time considered to be psychosomatic in nature, is now considered to be a valid medical condition in which early diagnosis and treatment can aid in alleviating or completely resolving symptoms. While frequently misdiagnosed as depression, differences have been noted in rate of cerebral blood flow.
CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression.
Fructose malabsorption and lactose intolerance; deficient fructose transport by the duodenum, or by the deficiency of the enzyme, lactase in the mucosal lining, respectively.
As a result of this malabsorption the saccharides reach the colon and are digested by bacteria which convert them to short chain fatty acids, CO2, and H2.
Approximately 50% of those afflicted exhibit the physical signs of irritable bowel syndrome.
Fructose malabsorption may play a role in the development of depressed mood. Fructose malabsorption should be considered in patients with symptoms of major depression.
Fructose and sorbitol reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression.
Endocrine System Disorders
Dysregulation of the endocrine system may present with various neuropsychiatric symptoms; irregularities in the hypothalamic-pituitary- adrenal (HPA) axis and the hypothalamic-pituitary-thyroid (HPT) axis have been shown in patients with primary depression.
HPT and HPA axes abnormalities observed in patients with depression:
HPT axes irregularities:
Alterations in thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH).
An abnormally high rate of antithyroid antibodies.
Elevated cerebrospinal fluid (CSF) TRH concentrations.
HPA axes irregularities:
Enlarged pituitary and adrenal gland size (organomegaly).
Also known as chronic adrenal insufficiency, hypocortisolism, and hypocorticism) is a rare endocrine disorder wherein the adrenal glands, located above the kidneys, produce insufficient steroid hormones (glucocorticoids and often mineralocorticoids).
Addison’s disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed.
Also known as hypercortisolism, is an endocrine disorder characterised by an excess of cortisol.
In the absence of prescribed steroid medications, it is caused by a tumour on the pituitary or adrenal glands, or more rarely, an ectopic hormone-secreting tumour.
Depression is a common feature in diagnosed patients and it often improves with treatment.
Thyroid and Parathyroid Glands
An autoimmune disease where the thyroid is overactive, resulting in hyperthyroidism and thyrotoxicosis.
Also known chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes.
Hashimoto’s thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies
Can affect calcium homeostasis, supplementation of which has completely resolved cases of depression in which hypoparathyroidism is the sole causative factor.
Tumours of the pituitary gland are fairly common in the general population with estimates ranging as high as 25%. Most tumours are considered to be benign and are often an incidental finding discovered during autopsy or as of neuroimaging in which case they are dubbed “incidentalomas”. Even in benign cases, pituitary tumours can affect cognitive, behavioural and emotional changes. Pituitary microadenomas are smaller than 10 mm in diameter and are generally considered benign, yet the presence of a microadenoma has been positively identified as a risk factor for suicide.
Patients with pituitary disease are diagnosed and treated for depression and show little response to the treatment for depression.
An overproduction of insulin causes reduced blood levels of glucose.
In one study of patients recovering from acute lung injury in intensive care, those patients who developed hypoglycaemia while hospitalised showed an increased rate of depression.
Central Nervous System Tumours
In addition to pituitary tumours, tumours in various locations in the central nervous system (CNS) may cause depressive symptoms and be misdiagnosed as depression.
Post Concussion Syndrome
Post-concussion syndrome (PCS), is a set of symptoms that a person may experience for weeks, months, or occasionally years after a concussion with a prevalence rate of 38-80% in mild traumatic brain injuries, it may also occur in moderate and severe cases of traumatic brain injury. A diagnosis may be made when symptoms resulting from concussion, depending on criteria, last for more than three to six months after the injury, in which case it is termed persistent post-concussive syndrome (PPCS). In a study of the prevalence of post concussion syndrome symptoms in patients with depression utilising the British Columbia Post-concussion Symptom Inventory: “Approximately 9 out of 10 patients with depression met liberal self-report criteria for a post-concussion syndrome and more than 5 out of 10 met conservative criteria for the diagnosis.” These self reported rates were significantly higher than those obtained in a scheduled clinical interview. Normal controls have exhibited symptoms of PCS as well as those seeking psychological services. There is considerable debate over the diagnosis of PCS in part because of the medico-legal and thus monetary ramifications of receiving the diagnosis.
Pseudobulbar affect (PBA) is an affective disinhibition syndrome that is largely unrecognised in clinical settings and thus often untreated due to ignorance of the clinical manifestations of the disorder; it may be misdiagnosed as depression. It often occurs secondary to various neurodegenerative diseases such as amyotrophic lateral sclerosis, and also can result from head trauma. PBA is characterised by involuntary and inappropriate outbursts of laughter and/or crying. PBA has a high prevalence rate with estimates of 1.5-2 million cases in the United States alone.
Multiple sclerosis is a chronic demyelinating disease in which the myelin sheaths of cells in the brain and spinal cord are irreparably damaged. Symptoms of depression are very common in patients at all stages of the disease and may be exacerbated by medical treatments, notably interferon beta-1a.
Various compounds have been shown to have neurotoxic effects many of which have been implicated as having a causal relationship in the development of depression.
There has been research which suggests a correlation between cigarette smoking and depression. The results of one recent study suggest that smoking cigarettes may have a direct causal effect on the development of depression. There have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts.
In a study conducted among nurses, those smoking between 1-24 cigarettes per day had twice the suicide risk; 25 cigarettes or more, 4 times the suicide risk, than those who had never smoked. In a study of 300,000 male US Army soldiers, a definitive link between suicide and smoking was observed with those smoking over a pack a day having twice the suicide rate of non-smokers.
Various medications have been suspected of having a causal relation in the development of depression; this has been classified as “organic mood syndrome”. Some classes of medication such as those used to treat hypertension, have been recognised for decades as having a definitive relationship with the development of depression.
Monitoring of those taking medications which have shown a relationship with depression is often indicated, as well as the necessity of factoring in the use of such medications in the diagnostic process.
Topical Tretinoin (Retin-A):
Derived from Vitamin A and used for various medical conditions such as in topical solutions used to treat acne vulgaris.
Although applied externally to the skin, it may enter the bloodstream and cross the blood brain barrier where it may have neurotoxic effects.
Proteins produced by the human body, three types have been identified alpha, beta and gamma.
Synthetic versions are utilised in various medications used to treat different medical conditions such as the use of interferon-alpha in cancer treatment and hepatitis C treatment.
All three classes of interferons may cause depression and suicidal ideation.
Chronic Exposure to Organophosphates
The neuropsychiatric effects of chronic organophosphate exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue.
Bipolar disorder is frequently misdiagnosed as major depression, and is thus treated with antidepressants alone which is not only not efficacious it is often contraindicated as it may exacerbate hypomania, mania, or cycling between moods. There is ongoing debate about whether this should be classified as a separate disorder because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a continuum between the two.
Nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. Insufficient or inadequate nutrition can have a profound effect on mental health. The emerging field of nutritional neuroscience explores the various connections between diet, neurological functioning and mental health.
Pyridoxal phosphate (PLP), the active form of B6, is a cofactor in the dopamine serotonin pathway, a deficiency in vitamin B6 may cause depressive symptoms.
Folate (vitamin B9) – Vitamin B12 cobalamin:
Low blood plasma and particularly red cell folate and diminished levels of vitamin B12 have been found in patients with depressive disorders.
Research suggests that oral doses of both folic acid (800 μg/(mcg) daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.
Long chain fatty acids:
Higher levels of omega-6 and lower levels of omega-3 fatty acids has been associated with depression and behavioural change.
Vitamin D deficiency is associated with depression
While the inability to fall asleep is often a symptom of depression, it can also in some instances serve as the trigger for developing a depressive disorder.
It can be transient, acute or chronic.
It can be a primary disorder or a co-morbid one.
Restless legs syndrome (RLS):
Also known as Wittmaack-Ekbom’s syndrome, is characterised by an irresistible urge to move one’s body to stop uncomfortable or odd sensations.
It most commonly affects the legs, but can also affect the arms or torso, and even phantom limbs.
Restless Leg syndrome has been associated with Major depressive disorder.
Adjusted odds ratio for diagnosis of major depressive disorder suggest a strong association between restless legs syndrome and major depressive disorder and/or panic disorder.
This is a sleep disorder characterised by pauses in breathing during sleep.
Each episode, called an apnoea, lasts long enough for one or more breaths to be missed; such episodes occur repeatedly throughout the sleep cycle.
Undiagnosed sleep apnoea may cause or contribute to the severity of depression.
Circadian rhythm sleep disorders:
Few clinicians are aware, and often goes untreated or are treated inappropriately, as when misdiagnosed as either primary insomnia or as a psychiatric condition.
Depression is a state of low mood and aversion to activity. It can affect a person’s thoughts, behaviour, motivation, feelings, and sense of well-being.
The core symptom of depression is said to be anhedonia, which refers to loss of interest or a loss of feeling of pleasure in certain activities that usually bring joy to people. Depressed mood is a symptom of some mood disorders such as major depressive disorder or dysthymia; it is a normal temporary reaction to life events, such as the loss of a loved one; and it is also a symptom of some physical diseases and a side effect of some drugs and medical treatments.
It may feature sadness, difficulty in thinking and concentration and a significant increase or decrease in appetite and time spent sleeping. People experiencing depression may have feelings of dejection, hopelessness and, sometimes, suicidal thoughts. It can either be short term or long term.
Depression is the leading cause of disability worldwide, the United Nations (UN) health agency reported, estimating that it affects more than 300 million people worldwide – the majority of them women, young people and the elderly. An estimated 4.4% of the global population suffers from depression, according to a report released by the UN World Health Organisation (WHO), which shows an 18 percent increase in the number of people living with depression between 2005 and 2015.
Depression is a major mental-health cause of disease burden. Its consequences further lead to significant burden in public health, including a higher risk of dementia, premature mortality arising from physical disorders, and maternal depression impacts on child growth and development. Approximately 76% to 85% of depressed people in low- and middle-income countries do not receive treatment; barriers to treatment include: inaccurate assessment, lack of trained health-care providers, social stigma and lack of resources.
The WHO has constructed guidelines – known as The Mental Health Gap Action Programme (mhGAP) – aiming to increase services for people with mental, neurological and substance-use disorders. Depression is listed as one of conditions prioritised by the programme. Trials conducted show possibilities for the implementation of the programme in low-resource primary-care settings dependent on primary-care practitioners and lay health-workers. Examples of mhGAP-endorsed therapies targeting depression include Group Interpersonal Therapy as group treatment for depression and “Thinking Health”, which utilises cognitive behavioural therapy to tackle perinatal depression. Furthermore, effective screening in primary care is crucial for the access of treatments. The mhGAP programme adopted its approach of improving detection rates of depression by training general practitioners. However, there is still weak evidence supporting this training.
History of the Concept
The Greco-Roman world used the tradition of the four humours to attempt to systematise sadness as “melancholia”.
The well-established idea of melancholy fell out of scientific favour in the 19th century.
Emil Kraepelin tried to give a scientific account of depression (German: das manisch-depressive Irresein) in 1896.
Adversity in childhood, such as bereavement, neglect, mental abuse, physical abuse, sexual abuse, or unequal parental treatment of siblings can contribute to depression in adulthood. Childhood physical or sexual abuse in particular significantly correlates with the likelihood of experiencing depression over the victim’s lifetime.
Life events and changes that may influence depressed moods include (but are not limited to): childbirth, menopause, financial difficulties, unemployment, stress (such as from work, education, family, living conditions etc.), a medical diagnosis (cancer, HIV, etc.), bullying, loss of a loved one, natural disasters, social isolation, rape, relationship troubles, jealousy, separation, or catastrophic injury. Adolescents may be especially prone to experiencing a depressed mood following social rejection, peer pressure, or bullying.
Changes in personality or in one’s social environment can affect levels of depression. High scores on the personality domain neuroticism make the development of depressive symptoms as well as all kinds of depression diagnoses more likely, and depression is associated with low extraversion. Other personality indicators could be: temporary but rapid mood changes, short term hopelessness, loss of interest in activities that used to be of a part of one’s life, sleep disruption, withdrawal from previous social life, appetite changes, and difficulty concentrating.
Depression may also be the result of healthcare, such as with medication induced depression. Therapies associated with depression include interferon therapy, beta-blockers, isotretinoin, contraceptives, cardiac agents, anticonvulsants, antimigraine drugs, antipsychotics, and hormonal agents such as gonadotropin-releasing hormone agonist.
Several drugs of abuse can cause or exacerbate depression, whether in intoxication, withdrawal, and from chronic use. These include alcohol, sedatives (including prescription benzodiazepines), opioids (including prescription pain killers and illicit drugs such as heroin), stimulants (such as cocaine and amphetamines), hallucinogens, and inhalants.
Depressed mood can be the result of a number of infectious diseases, nutritional deficiencies, neurological conditions, and physiological problems, including hypoandrogenism (in men), Addison’s disease, Cushing’s syndrome, hypothyroidism, hyperparathyroidism, Lyme disease, multiple sclerosis, Parkinson’s disease, chronic pain, stroke, diabetes, and cancer.
A number of psychiatric syndromes feature depressed mood as a main symptom. The mood disorders are a group of disorders considered to be primary disturbances of mood. These include major depressive disorder (MDD; commonly called major depression or clinical depression) where a person has at least two weeks of depressed mood or a loss of interest or pleasure in nearly all activities; and dysthymia, a state of chronic depressed mood, the symptoms of which do not meet the severity of a major depressive episode.
Another mood disorder, bipolar disorder, features one or more episodes of abnormally elevated mood, cognition, and energy levels, but may also involve one or more episodes of depression. When the course of depressive episodes follows a seasonal pattern, the disorder (major depressive disorder, bipolar disorder, etc.) may be described as a seasonal affective disorder.
Outside the mood disorders: borderline personality disorder often features an extremely intense depressive mood; adjustment disorder with depressed mood is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioural symptoms are significant but do not meet the criteria for a major depressive episode; and posttraumatic stress disorder, a mental disorder that sometimes follows trauma, is commonly accompanied by depressed mood.
Researchers have begun to conceptualise ways in which the historical legacies of racism and colonialism may create depressive conditions.
Measures of Depression
Measures of depression as an emotional disorder include (but are not limited to) the Beck Depression Inventory-11 and the 9-item depression scale in the Patient Health Questionnaire.
Both of these measures are psychological tests that ask personal questions of the participant, and have mostly been used to measure the severity of depression. The Beck Depression Inventory (BDI) is a self-report scale that helps a therapist identify the patterns of depression symptoms and monitor recovery. The responses on this scale can be discussed in therapy to devise interventions for the most distressing symptoms of depression. Several studies, however, have used these measures to also determine healthy individuals who are not suffering from depression as a mental disorder, but as an occasional mood disorder. This is substantiated by the fact that depression as an emotional disorder displays similar symptoms to minimal depression and low levels of mental disorders such as major depressive disorder; therefore, researchers were able to use the same measure interchangeably. In terms of the scale, participants scoring between 0-13 and 0-4 respectively were considered healthy individuals.
Another measure of depressed mood would be the IWP Multi-affect Indicator. It is a psychological test that indicates various emotions, such as enthusiasm and depression, and asks for the degree of the emotions that the participants have felt in the past week. There are studies that have used lesser items from the IWP Multi-affect Indicator which was then scaled down to daily levels to measure the daily levels of depression as an emotional disorder.
Alcohol can be a depressant which slows down some regions of the brain, like the prefrontal and temporal cortex, negatively affecting rationality and memory. It also lowers the level of serotonin in the brain, which could potentially lead to higher chances of depressive mood.
The connection between the amount of alcohol intake, level of depressed mood, and how it affects the risks of experiencing consequences from alcoholism, were studied in a research done on college students. The study used 4 latent, distinct profiles of different alcohol intake and level of depression; Mild or Moderate Depression, and Heavy or Severe Drinkers. Other indicators consisting of social factors and individual behaviours were also taken into consideration in the research. Results showed that the level of depression as an emotion negatively affected the amount of risky behaviour and consequence from drinking, while having an inverse relationship with protective behavioural strategies, which are behavioural actions taken by oneself for protection from the relative harm of alcohol intake. Having an elevated level of depressed mood does therefore lead to greater consequences from drinking.
Social abuse, such as bullying, are defined as actions of singling out and causing harm on vulnerable individuals. In order to capture a day-to-day observation of the relationship between the damaging effects of social abuse, the victim’s mental health and depressive mood, a study was conducted on whether individuals would have a higher level of depressed mood when exposed to daily acts of negative behaviour. The result concluded that being exposed daily to abusive behaviours such as bullying has a positive relationship to depressed mood on the same day.
The study has also gone beyond to compare the level of depressive mood between the victims and non-victims of the daily bullying. Although victims were predicted to have a higher level of depressive mood, the results have shown otherwise that exposure to negative acts has led to similar levels of depressive mood, regardless of the victim status. The results therefore have concluded that bystanders and non-victims feel as equally depressed as the victim when being exposed to acts such as social abuse.
Divergent thinking is defined as a thought process that generates creativity in ideas by exploring many possible solutions. Having a depressed mood will significantly reduce the possibility of divergent thinking, as it reduces the fluency, variety and the extent of originality of the possible ideas generated.
However, some depressive mood disorders might have a positive effect for creativity. Upon identifying several studies and analysing data involving individuals with high levels of creativity, Christa Taylor was able to conclude that there is a clear positive relationship between creativity and depressive mood. A possible reason is that having a low mood could lead to new ways of perceiving and learning from the world, but it is unable to account for certain depressive disorders. The direct relationship between creativity and depression remains unclear, but the research conducted on this correlation has shed light that individuals who are struggling with a depressive disorder may be having even higher levels of creativity than a control group, and would be a close topic to monitor depending on the future trends of how creativity will be perceived and demanded.
Stress Management Techniques
There are empirical evidences of a connection between the type of stress management techniques and the level of daily depressive mood.
Problem-focused coping leads to lower level of depression. Focusing on the problem allows for the subjects to view the situation in an objective way, evaluating the severity of the threat in an unbiased way, thus it lowers the probability of having depressive responses. On the other hand, emotion-focused coping promotes a depressed mood in stressful situations. The person has been contaminated with too much irrelevant information and loses focus on the options for resolving the problem. They fail to consider the potential consequences and choose the option that minimises stress and maximises well-being.
Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to a diagnosis of a psychiatric or medical condition which may benefit from treatment. The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicated that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. Physical activity can have a protective effect against the emergence of depression.
Physical activity can also decrease depressive symptoms due to the release of neurotrophic proteins in the brain that can help to rebuild the hippocampus that may be reduced due to depression. Also yoga could be considered an ancillary treatment option for patients with depressive disorders and individuals with elevated levels of depression.
Reminiscence of old and fond memories is another alternative form of treatment, especially for the elderly who have lived longer and have more experiences in life. It is a method that causes a person to recollect memories of their own life, leading to a process of self-recognition and identifying familiar stimuli. By maintaining one’s personal past and identity, it is a technique that stimulates people to view their lives in a more objective and balanced way, causing them to pay attention to positive information in their life stories, which would successfully reduce depressive mood levels.
Self-help books are a growing form of treatment for peoples physiological distress. There may be a possible connection between consumers of unguided self-help books and higher levels of stress and depressive symptoms. Researchers took many factors into consideration to find a difference in consumers and non-consumers of self-help books. The study recruited 32 people between the ages of 18 and 65; 18 consumers and 14 non-consumers, in both groups 75% of them were female. Then they broke the consumers into 11 who preferred problem-focused and 7 preferred growth-oriented. Those groups were tested for many things including cortisol levels, depressive symptomatology, and stress reactivity levels. There were no large differences between consumers of self-help books and non-consumers when it comes to diurnal cortisol level, there was a large difference in depressive symptomatology with consumers having a higher mean score. The growth-oriented group has higher stress reactivity levels than the problem-focused group. However, the problem-focused group shows higher depressive symptomatology.
Anxiety and Depression in Children and Adolescents: Assessment, Intervention, and Prevention.
Author(s): Thomas J. Huberty..
Edition: First (1st).
Type(s): Hardcover and eBook.
Although generally considered adult disorders, anxiety and depression are widespread among children and adolescents, affecting academic performance, social development, and long-term outcomes. They are also difficult to treat and, especially when they occur in tandem, tend to fly under the diagnostic radar.
Anxiety and Depression in Children and Adolescents offers a developmental psychology perspective for understanding and treating these complex disorders as they manifest in young people. Adding the school environment to well-known developmental contexts such as biology, genetics, social structures, and family, this significant volume provides a rich foundation for study and practice by analyzing the progression of pathology and the critical role of emotion regulation in anxiety disorders, depressive disorders, and in combination. Accurate diagnostic techniques, appropriate intervention methods, and empirically sound prevention strategies are given accessible, clinically relevant coverage. Illustrative case examples and an appendix of forms and checklists help make the book especially useful.
Featured in the text:
Developmental psychopathology of anxiety, anxiety disorders, depression, and mood disorders.
Differential diagnosis of the anxiety and depressive disorders.
Assessment measures for specific conditions.
Age-appropriate interventions for anxiety and depression, including CBT and pharmacotherapy.
Multitier school-based intervention and community programmes.
Building resilience through prevention.
Anxiety and Depression in Children and Adolescents is an essential reference for practitioners, researchers, and graduate students in school and clinical child psychology, mental health and school counselling, family therapy, psychiatry, social work, and education.