While racing thoughts are most commonly described in people with bipolar disorder and sleep apnoea, they are also common with anxiety disorders, OCD, and other psychiatric disorders such as attention deficit hyperactivity disorder. Racing thoughts are also associated with sleep deprivation, hyperthyroidism and the use of amphetamines.
Description
Racing thoughts may be experienced as background or take over a person’s consciousness. Thoughts, music, and voices might be zooming through one’s mind as they jump tangentially from one to the next. There also might be a repetitive pattern of voice or of pressure without any associated “sound”. It is a very overwhelming and irritating feeling, and can result in losing track of time. In some cases, it may also be frightening to the person experiencing it, as there is a loss of control. If one is experiencing these thoughts at night when going to sleep, they may suddenly awaken, startled and confused by the very random and sudden nature of the thoughts.
Racing thoughts differ in manifestation according to the individual’s perspective. These manifestations can vary from unnoticed or minor distractions to debilitating stress, preventing the sufferer from maintaining a thought.
Generally, racing thoughts are described by an individual who has had an episode where the mind uncontrollably brings up random thoughts and memories and switches between them very quickly. Sometimes they are related, as one thought leads to another; other times they seem completely random. A person suffering from an episode of racing thoughts has no control over their train of thought, and it stops them from focusing on one topic or prevents sleeping.
Associated Conditions
The causes of racing thoughts are most often associated with anxiety disorders, but many influences can cause these rapid, racing thoughts. There are also many associated conditions, in addition to anxiety disorders, which can be classified as having secondary relationships with causing racing thoughts. The conditions most commonly linked to racing thoughts are bipolar disorder, anxiety disorder, attention deficit hyperactivity disorder, sleep deprivation, amphetamine dependence, and hyperthyroidism.
Anxiety Disorders
Racing thoughts associated with anxiety disorders can be caused by many different conditions, such as obsessive-compulsive disorder (OCD), panic disorder, generalised anxiety disorder, or posttraumatic stress disorder.
In people with OCD, racing thoughts can be brought on by stressors, or triggers, causing disturbing thoughts in the individual. These disturbing thoughts, then, result in compulsions characterising OCD in order to lower the stress and gain some sort of control over these stressful, racing thoughts.
Panic disorder is an anxiety disorder characterised by repeated panic attacks of fear or nervousness, lasting several minutes. During these panic attacks, the response is out of proportion to the situation. The racing thoughts may feel catastrophic and intense, but they are a symptom of the panic attack and must be controlled in order to soothe the panic and minimise the panic attack.
Generalised anxiety disorder (GAD) is a neurological anxiety disorder that involves uncontrollable and excessive worrying about irrational topics or problems. These stressful thoughts must be present for at least six months in order to be diagnosed as GAD. Along with other symptoms, racing thoughts is one of the most common ones. With GAD, there is an inability to relax or let thoughts or worries go, persistent worrying and obsessions about small concerns that are out of proportion to the result, and even worrying about their excessive worrying.
Bipolar Disorder
Racing thoughts can be brought on by bipolar disorder, defined by mood instability that range from extreme emotional highs, mania, to severe depression. During the manic phase of bipolar disorder is when racing thoughts usually occur. Disjointed, constantly changing thoughts with no underlying theme can be a sign of the manic phase of bipolar disorder. Manic thoughts can prevent performance of daily routines due to their rapid, unfocused and overwhelming nature. Racing thoughts in people with bipolar disorder are generally accompanied with other symptoms associated with this disorder.
Amphetamines
Amphetamines are used as a stimulant to trigger the central nervous system, increasing heart rate and blood pressure while decreasing appetite. Since amphetamines are a stimulant, use of these drugs result in a state that resembles the manic phase of bipolar disorder and also produces similar symptoms, as stated above.
Attention Deficit Hyperactivity Disorder
Racing thoughts associated with ADHD is most common in adults. With ADHD, racing thoughts can occur and tend to cause insomnia. Racing thoughts in people with ADHD tend to be rapid, unstable thoughts which do not follow any sort of pattern, similar to racing thoughts in people with bipolar disorder. Medications used to treat ADHD, such as Adderall or Methylphenidate, can be prescribed to patients with ADHD to calm these racing thoughts, most commonly in the morning when people wake up but just as well in the evening before sleep.
Lack of Sleep
Racing thoughts, also referred to as “racing mind”, may prevent a person from falling asleep. Chronic sleep apnoea and prolonged disturbed sleep patterns may also induce racing thoughts. Treatment for sleep apnoea and obstructive airway disorder can improve airflow and improve sleep resulting in improved brain and REM (rapid eye movement) function and reduced racing thought patterns.
Hyperthyroidism
Hyperthyroidism is a condition in which the thyroid gland produces too much thyroid hormone, thyroxin. This overabundance of thyroxin causes irregular and rapid heartbeat, irritability, weight loss, nervousness, anxiety and racing thoughts. The anxiety and inability to focus is very common in hyperthyroidism and leads to racing thoughts, as well as panic attacks and difficulty concentrating.
Frequency
Anxiety disorder, the most common mental illness in the United States, affects 40 million people, ages 10 and older; this accounts for 18% of the US population. Most people suffering from anxiety disorder report some form of racing thoughts symptom.
The prevalence of OCD in every culture studied is at least 2% of the population, and the majority of those have obsessions, or racing thoughts. With these reports, estimates of more than 2 million people in the United States (as of 2000) suffer from racing thoughts.
Treatment
There are various treatments available to calm racing thoughts, some of which involve medication. One type of treatment involves writing out the thoughts onto paper. Some treatments suggest using activities, such as painting, cooking, and other hobbies, to keep the mind busy and distract from the racing thoughts. Exercise may be used to tire the person, thereby calming their mind. When racing thoughts are anxiety induced during panic or anxiety attacks, it is recommended that the person wait it out. Using breathing and meditation techniques to calm the breath and mind simultaneously is another tool for handling racing thoughts induced by anxiety attacks. Mindfulness meditation has also shown to help with racing thoughts by allowing practitioners to face their thoughts head-on, without reacting.
While all of these techniques can be useful to cope with racing thoughts, it may prove necessary to seek medical attention and counsel. Since racing thoughts are associated with many other underlying mental illnesses, such as bipolar disorder, anxiety disorder, and ADHD, medications used commonly to treat these disorders will help calm racing thoughts in patients.
Treatment for the underlying causes of racing thoughts is helpful and useful in order to calm the racing thoughts more permanently. For example, in people with ADHD, medications used to promote focus and calm distracting thoughts, will help them with their ADHD.
Some obstructive airway disorders may be relieved with nasal septoplasty which can improve sleep and lead to a reduction of racing mind. Insomnia may increase racing thoughts and those effected will find sleep apnoea treatment and nasal surgery helpful to eliminate their racing thoughts.
It is important to look at the underlying defect that may be causing racing thoughts in order to prevent them in the long-term.
The International Society for Bipolar Disorders (ISBD) is a non-profit organisation based in Pittsburgh, Pennsylvania, where it was founded 17 June 1999. The society focuses on research and education in bipolar disorders.
The society has a membership consisting of mental health professionals and patients and their family members representing 50 countries. The mission of the society is to advance the treatment of all aspects of bipolar disorder, thereby improving patient outcomes and quality of life, through fostering international collaboration in education and research. The society hosts biennial professional meetings and offers educational programmes. The official journal of the society is Bipolar Disorders and a subscription is included with membership.
Brief History
The ISBD was founded at the 3rd International Conference on Bipolar Disorder, in Pittsburgh, Pennsylvania, in June 1999 by David J. Kupfer and Thomas Detre (University of Pittsburgh Medical Centre). In September 1999, the official peer-reviewed society journal, Bipolar Disorders, published its first issue.
The ISBD held its first meeting in Sydney, Australia, in February 2004 with over 400 participants in attendance. The society held its second meeting in August 2006 in Edinburgh, Scotland, with over 600 attendees. As of 2013, the society has over 800 members in 50 countries with an elected board representing 15 countries.
Educational Programmes
The society supports the following educational initiatives:
The Psychiatric Trainee Support programme:
Offers psychiatric trainees a free two-year membership in the society in order to enhance knowledge of bipolar disorder among this group, narrow the gap between bipolar research and clinical practice, and ultimately to improve diagnosis, treatment and outcomes for patients with bipolar disorder.
These supported memberships are open to psychiatric residents, postgraduate students and junior faculty up to the Assistant Professor or equivalent level with less than five years as faculty in their career trajectory.
The programmes seek to support 70% of trainees from developing countries.
The Samuel Gershon Awards for Junior Investigators:
Named in honour of Samuel Gershon, past ISBD President and pioneer of early lithium research, offer four awards for original research submissions.
Awards are based on the originality of the content, as well as the significance of the findings reported, and are evaluated by an international scientific panel under the auspices of the ISBD.
These awards are open to psychiatric trainees, postgraduate students and junior faculty up to the assistant professor rank from around the world.
The awards are presented in conjunction with the society’s biennial meeting where the winners present their research in a special session showcasing the work of junior people in the field.
The ISBD Research Fellowship for Junior Investigators:
Provides an opportunity for the recipient to travel to another facility to get training in a particular type of research methodology (i.e. brain imaging, genetics, clinical trials, etc.).
The fellowship is intended to cover up to six months support for salary, travel, or some combination of these costs as they are incurred in pursuit of additional training.
This could take the form of summer programs, participation in smaller prospective studies, or through some other opportunity.
Conferences
The society organises biennial meetings that provides updates on topics such as epidemiology, pharmacotherapy, psychotherapies, genetics, neurobiology, imaging research, and bipolar disorder in special populations.
It asks about 32 behaviours and mental states that are either aspects of hypomania or features associated with mood disorders. It uses short phrases and simple language, making it easy to read. The University of Zurich holds the copyright, and the HCL-32 is available for use at no charge. More recent work has focused on validating translations and testing whether shorter versions still perform well enough to be helpful clinically. Recent meta-analyses find that it is one of the most accurate assessments available for detecting hypomania, doing better than other options at recognising bipolar II disorder.
Development and Brief History
The Hypomania Checklist was built as a more efficient screening measure for hypomania, to be used both in epidemiological research and in clinical use. Existing measures for bipolar disorder focused on identifying personality factors and symptom severity instead of the episodic nature of hypomania or the possible negative consequences in behavioural, affective, or cognitive changes associated. These measures were mostly used in non-clinical populations to identify individuals at risk and were not used as screening instruments. The HCL-32 is a measure intended to have high sensitivity to direct clinicians from many countries to diagnosing individuals in a clinical population with bipolar disorder, specifically bipolar II disorder.
Initially developed by Jules Angst and Thomas Meyer in German, the questionnaire was translated into English and translated back to German to ensure accuracy. The English version of the HCL has been used as the basis for translation in other languages through the same process. The original study that used the HCL in an Italian and a Swiss sample noted the measure’s high sensitivity and a lower sensitivity than other used measures.
The scale includes a checklist of 32 possible symptoms of hypomania, each rated yes or no. The rating “yes” would mean the symptom is present or this trait is “typical of me,” and “no” would mean that the symptom is not present or “not typical” for the person.
Limitations
The HCL suffers from the same problems as other self-report inventories, in that scores can be easily exaggerated or minimised by the person completing them. Like all questionnaires, the way the instrument is administered can influence the final score. If a patient is asked to fill out the form in front of other people in a clinical environment, for instance, social expectations may elicit a different response compared to administration via a postal survey.
Similar reliability scores were found when only using 16 item assessments versus the traditional 32-item format of the HCL-32. A score of at least 8 items was found valid and reliable for distinguishing Bipolar Disorder and Major Depressive Disorder. In a study, 73% of patients who completed the HCL-32 R1 were true bipolar cases identified as potential bipolar cases. However, the HCL-32 R1 does not accurately differentiate between Bipolar I and Bipolar II. However, the 16-item HCL has not been tested as a standalone section in a hospital setting. In addition, while the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between bipolar I and bipolar-II disorders. The HCL-32 has not been compared with other commonly used screening tools for bipolar disorder, such as the Young Mania Rating Scale (YMRS)and the General Behaviour Inventory (GBI). The online version of the HCL has been shown to be as reliable as the paper version.
Bipolar disorder in children, or paediatric bipolar disorder (PBD), is a controversial mental disorder in children and adolescents that is mainly diagnosed in the United States, and is hypothesized to be like bipolar disorder (BD) in adults, thus is proposed as an explanation for extreme changes in mood and behaviour accompanying periods of depressed or irritable moods and periods of elevated moods so called manic or hypomanic episodes.
These shifts are sometimes quick, but usually are gradual. The average age of onset of paediatric bipolar disorder is unclear, but the risk increases with the onset of puberty. Bipolar disorder is rare in childhood. Paediatric bipolar disorder is typically more severe and has a poorer prognosis than bipolar disorder with onset in late-adolescence or adulthood.
The DSM has specified that the criteria for bipolar disorder can be applied to children since 1980. However, the exact criteria for diagnosing paediatric bipolar disorder remains controversial and heavily debated. There are big differences in how commonly it is diagnosed across clinics and in different countries. There has been a rapid increase in research on the topic, but training and clinical practice lag behind.
Identifying bipolar disorder in youth is challenging. Children often exhibit chronic rather than episodic mania periods. Almost always, these chronic problems have causes other than bipolar disorder. The criteria for paediatric bipolar disorder can also often be masked by developmental differences. Comorbid disorders make determining what symptoms are signs of bipolar disorder and which are due to other disorders (e.g. OCD, ADHD, disruptive behaviour problems) difficult, leading to complications in treatment. For example, a common treatment for OCD are serotonin re-uptake inhibitors (SRIs), however, SRIs can lead to mood instability and worsening bipolar disorder.[5] The most common misdiagnosis for ADHD in the USA is paediatric bipolar disorder due to hyperactivity being described as prolonged periods of mania. Empirical research conducted in 2004 found that “bipolar disorder (in preadolescence) was initially misdiagnosed in 12 out of 24 youths” (Mahoney, 2004). This is a dangerous misdiagnosis due to the vastly different treatment forms. Firstly, ADHD does not require mood stabilisers like paediatric bipolar disorder. Secondly, the stimulants given to treat ADHD have been shown to cause psychosis and exacerbate mania in paediatric bipolar disorder (Wendling, 2009). This misuse of medication can lead to mood episodes, suicidality, and hospitalisation.
Brief History
Descriptions of children with symptoms similar to contemporary concepts of mania date back to the 18th century. In 1898, a detailed psychiatric case history was published about a 13-year-old that met Jean-Pierre Falret and Jules Baillarger’s criteria for folie circulaire, which is congruent to the modern conception of bipolar I disorder.
In Emil Kraepelin’s descriptions of bipolar disorder in the 1920s, which he called “manic depressive insanity”, he noted the rare possibility that it could occur in children. In addition to Kraepelin, Adolf Meyer, Karl Abraham, and Melanie Klein were some of the first to document bipolar disorder symptoms in children in the first half of the 20th century. It was not mentioned much in English literature until the 1970s when interest in researching the subject increased. It became more accepted as a diagnosis in children in the 1980s after the DSM-III (1980) specified that the same criteria for diagnosing bipolar disorder in adults could also be applied to children.
Recognition came twenty years after, with epidemiological studies showing that approximately 20% of adults with bipolar disorder already had symptoms in childhood or adolescence. Nevertheless, onset before age 10 was thought to be rare, below 0.5% of the cases. During the second half of the century misdiagnosis with schizophrenia was not rare in the non-adult population due to common co-occurrence of psychosis and mania, this issue diminishing with an increased following of the DSM criteria in the last part of the 20th century.
Epidemiology
The prevalence of bipolar in youth is estimated at 2%.
Diagnosis
Diagnosis is made based on a clinical interview by a psychiatrist or other licensed mental health practitioner. There are no blood tests or brain scans to diagnose bipolar disorder. Obtaining information on family history and the use of questionnaires and checklists are helpful in making an accurate diagnosis. Commonly used assessment tools include the:
In both the American Psychiatric Association’s DSM-5 and the World Health Organisation’s ICD-10, the same criteria used to diagnose bipolar disorder in adults are used to make the diagnosis in children with some adjustments to account for differences in age and developmental stage. For example, the DSM-5 specifies that in children, depressive episodes can manifest as persistently irritable moods.
In diagnosing manic episodes, it is important to compare the changes in mood and behaviour to the child’s normal mood and behaviours at baseline instead of to other children or adults. For example, grandiosity (i.e. unrealistic overestimation of one’s intelligence, talent, or abilities) is normal at varying degrees during childhood and adolescence. Therefore, grandiosity is only considered symptomatic of mania in children when the beliefs are held despite being presented with concrete evidence otherwise or when they lead to a child attempting activities that are clearly dangerous, and most importantly, when the grandiose beliefs are an obvious change from that particular child’s normal self-view in between episodes.
Controversy
The diagnosis of childhood bipolar disorder is controversial, although it is recognised that bipolar disorder typical symptoms are dysfunctional and have negative consequences for minors suffering them. Main discussion is centred on whether what is called bipolar disorder in children refers to the same disorder than when diagnosing adults, and the related question on whether adults’ criteria for diagnosis are useful and accurate when applied to children. More specifically, main discussion over diagnosis in children circles around mania symptomatology and its differences between children and adults.
Diagnostic criteria may not correctly separate children with bipolar disorder from other problems such as ADHD, and emphasize fast mood cycles.
Treatment
Medications can produce important side effects, so interventions have been recommended to be closely monitored and families of patients to be informed of the different possible problems that can arise. Atypical antipsychotics are more effective than mood stabilizers, but have more side effects. Typical antipsychotics may produce weight gains as well as other metabolic problems, including diabetes mellitus type 2 and hyperlipidaemia. Extrapyramidal secondary effects may appear with these medications. These include tardive dyskinesia, a difficult-to-treat movement disorder (dyskinesia) that can appear after long-term use of antipsychotics. Liver and kidney damage are a possibility with mood stabilisers.
Psychological treatment usually includes some combination of education on the disease, group therapy and cognitive behavioural therapy (CBT). Children with bipolar disorder and their families are informed, in ways accordingly to their age and family role, about the different aspects of bipolar disorder and its management including causes, signs and symptoms and treatments. Group therapy aims to improve social skills and manage group conflicts, with role-playing as a critical tool. Finally, cognitive-behavioural training is directed towards the participants having a better understanding and control over their emotions and behaviours.
Lithium or Divalproex is recommended for first-line treatment.
Partial (minimal to moderate) improvement with monotherapy, augment with another of the first-line recommendations.
Stage 2: Monotherapy with an alternative drug, then augmentation.
Stage 3: Possible medication combinations – lithium plus Divalproex, lithium plus atypical, or Divalproex plus atypical.
Stage 4: Combination of 2-3 mood stabilisers.
Stage 5: Alternate monotherapy with oxcarbazepine, ziprasidone, or aripiprazole (all Level D).
Stage 6: For nonresponse or intolerable side effects – clozapine for children or adolescents, or electroconvulsive therapy (ECT) for adolescents only.
BPD I, manic or mixed, with psychosis:
Stage 1: Same as BPD I without psychosis except for first-line treatment warrants a combination of mood stabiliser and an atypical antipsychotic.
Stages 2-4: Varying combinations and augmentations.
Stage 5: Alternate monotherapy (oxcarbazepine) plus an atypical antipsychotic.
Prognosis
Chronic medication is often needed, with relapses of individuals reaching rates over 90% in those not following medication indications and almost to 40% in those complying with medication regimens in some studies. Compared to adults, a juvenile onset has in general a similar or worse course, although age of onset predicts the duration of the episodes more than the prognosis. A risk factor for a worse outcome is the existence of additional (comorbid) pathologies.
Children with bipolar disorder are more likely to suicide than other children.
The Schedule for Affective Disorders and Schizophrenia (SADS) is a collection of psychiatric diagnostic criteria and symptom rating scales originally published in 1978.
It is organised as a semi-structured diagnostic interview. The structured aspect is that every interview asks screening questions about the same set of disorders regardless of the presenting problem; and positive screens get explored with a consistent set of symptoms. These features increase the sensitivity of the interview and the inter-rater reliability (or reproducibility) of the resulting diagnoses. The SADS also allows more flexibility than fully structured interviews: Interviewers can use their own words and rephrase questions, and some clinical judgment is used to score responses.
There are three versions of the schedule:
The regular SADS;
The lifetime version (SADS-L); and
A version for measuring the change in symptomology (SADS-C).
Although largely replaced by more structured interviews that follow diagnostic criteria such as DSM-IV and DSM-5, and specific mood rating scales, versions of the SADS are still used in some research papers today.
Relationship with the Research Diagnostic Criteria
The SADS was developed by the same group of researchers as the Research Diagnostic Criteria (RDC). While the RDC is a list of diagnostic criteria for psychiatric disorders, the SADS interview allows diagnoses based on RDC criteria to be made, and also rates subject’s symptoms and level of functioning.
K-SADS
The K-SADS (or Kiddie-SADS) is a version of the SADS adapted for school-aged children of 6–18 years. There are various different versions of the K-SADS, each varying slightly in terms of disorders and specific symptoms covered, as well as the scale range used. All of the variations are still semi-structured interviews, giving the interviewer more flexibility about how to phrase and probe items, while still covering a consistent set of disorders.
The K-SADS-E (Epidemiological version) was developed for epidemiological research. It focused on current issues and episodes only. Most of the items used a four point rating scale.
The K-SADS-PL (Present and Lifetime version) is administered by interviewing the parent(s), the child, and integrating them into a summary rating that includes parent report, child report, and clinical observations during the interview. The interview covers both present issues (i.e., the reason the family is seeking an evaluation) as well as past episodes of the disorders. Most items use a three point rating scale for severity (not present, subthreshold, and threshold – which combines both moderate and severe presentations). It has been used with preschool as well as school-aged children. A 2009 working draft removed all reference to the DSM-III-R criteria (which were replaced with the publication of the DSM-IV in 1994) and made some other modifications. A DSM-5 version is being prepared and validated.
The WASH-U K-SADS (Washington University version) added items to the depression and mania modules and used a six point severity rating for severity.
The cause and mechanism of bipolar disorder is not yet known, and the study of its biological origins is ongoing. Although no single gene causes the disorder, a number of genes are linked to increase risk of the disorder, and various gene environment interactions may play a role in predisposing individuals to developing bipolar disorder. Neuroimaging and post-mortem studies have found abnormalities in a variety of brain regions, and most commonly implicated regions include the ventral prefrontal cortex and amygdala. Dysfunction in emotional circuits located in these regions have been hypothesized as a mechanism for bipolar disorder. A number of lines of evidence suggests abnormalities in neurotransmission, intracellular signalling, and cellular functioning as possibly playing a role in bipolar disorder.
Studies of bipolar disorder, particularly neuroimaging studies, are vulnerable to the confounding effects such as medication, comorbidity, and small sample size, leading to underpowered independent studies, and significant heterogeneity.
Brain imaging studies have revealed differences in the volume of various brain regions between patients with bipolar disorder and healthy control subjects.
Aetiology
Genetic
The etiology of bipolar disorder is unknown. The overall heritability of bipolar is estimated at 79%-93%, and first degree relatives of bipolar probands have a relative risk of developing bipolar around 7-10. While the heritability is high, no specific genes have been conclusively associated with bipolar, and a number of hypothesis have been posited to explain this fact. “The polygenic common rare variant” hypothesis suggests that a large number of risk conferring genes are carried in a population, and that a disease manifests when a person has a sufficient number of these genes. The “multiple rare variant” model suggests that multiple genes that are rare in the population are capable of causing a disease, and that carrying one or a few can lead to disease. The familial transmission of mania and depression are largely independent of each other. This raises the possibility that bipolar is actually two biologically distinct but highly comorbid conditions.
A number of genome wide associations have been reported, including CACNA1C and ODZ4, and TRANK1. Less consistently reported loci include ANK3 and NCAN, ITIH1, ITIH3 and NEK4. Significant overlaps with schizophrenia have been reported at CACNA1C, ITIH, ANK3, and ZNF804A. This overlap is congruent with the observation that relatives of probands with schizophrenia are at higher risk for bipolar disorder and vice versa.
In light of associations between bipolar and circadian abnormalities (such as decreased need for sleep and increased sleep latency), polymorphisms in the CLOCK gene have been tested for association, although findings have been inconsistent, and one meta analysis has reported no association with either bipolar or major depressive disorder. Other circadian genes associated with bipolar at relaxed significance thresholds include ARTNL, RORB, and DEC1. One meta analysis reported a significant association of the short allele of the serotonin transporter, although the study was specific to European populations. Two polymorphisms in the tryptophan hydroxylase 2 gene have been associated with bipolar disorder. NFIA has been linked with seasonal patterns of mania.
One particular SNP located on CACNA1C that confers risk for bipolar disorder is also associated with elevated CACNA1C mRNA expression in the prefrontal cortex, and increased calcium channel expression in neurons made from patient induced pluripotent stem cells.
No significant association exists for the BDNF Val66Met allele and bipolar disorder, except possibly in a subgroup of bipolar II cases, and suicide.
Due to the inconsistent findings in GWAS, multiple studies have undertaken the approach of analysing SNPs in biological pathways. Signalling pathways traditionally associated with bipolar disorder that have been supported by these studies include CRH signalling, cardiac β-adrenergic signalling, phospholipase C signalling, glutamate receptor signalling, cardiac hypertrophy signalling, Wnt signalling, notch signalling, and endothelin 1 signalling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the dorsolateral prefrontal cortex portion of the brain in post-mortem studies, CACNA1C, GNG2, and ITPR2.
Advanced paternal age has been linked to a somewhat increased chance of bipolar disorder in offspring, consistent with a hypothesis of increased new genetic mutations.
A meta-analysis was performed to determine the association between bipolar disorder and oxidative DNA damage measured by 8-hydroxy-2′-8-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Levels of 8-OHdG and 8-oxodG are widely used as measures of oxidative stress in mental illnesses. It was determined from this meta-analysis that oxidative DNA damage was significantly increased in bipolar disorder.
Environmental
Manic episodes can be produced by sleep deprivation in around 30% of people with bipolar. While not all people with bipolar demonstrate seasonality of affective symptoms, it is a consistently reported feature that supports theories of circadian dysfunction in bipolar.
Risk factors for bipolar include obstetric complications, abuse, drug use, and major life stressors.
The “kindling model” of mood disorders suggests that major environmental stressors trigger initial mood episodes, but as mood episodes occur, weaker and weaker triggers can precipitate an affective episode. This model was initially created for epilepsy, to explain why weaker and weaker electrical stimulation was necessary to elicit a seizure as the disease progressed. While parallels have been drawn between bipolar disorder and epilepsy, supporting the kindling hypothesis, this model is generally not supported by studies directly assessing it in bipolar subjects.
Neurological Disorders
Mania occurs secondary to neurological conditions between a rate of 2% to 30%. Mania is most commonly seen in right sided lesions, lesions that disconnect the prefrontal cortex, or excitatory lesions in the left hemisphere.
Diseases associated with “secondary mania” include Cushing’s disease, dementia, delirium, meningitis, hyperparathyroidism, hypoparathyroidism, thyrotoxicosis, multiple sclerosis, Huntington’s disease, epilepsy, neurosyphilis, HIV dementia, uraemia, as well as traumatic brain injury and vitamin B12 deficiency.
Pathophysiology
Neurobiological and Neuroanatomical Models
The main loci of neuroimaging and neuropathological findings in bipolar have been proposed to constitute dysfunction in a “visceromotor” network, composed of the mPFC, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), hippocampus, amygdala, hypothalamus, striatum and thalamus.
A model of functional neuroanatomy produced by a workgroup led by Stephen M. Strakowski concluded that bipolar was characterized by reduced connectivity, due to abnormal pruning or development, in the prefrontal-striatal-pallidal-thalamic-limbic network leading to dysregulated emotional responses. This model was supported by a number of common neuroimaging findings. Dysregulation of limbic structures is evinced by the fact that hyperactivity in the amygdala in response to facial stimuli has been consistently reported in mania. While amygdala hyperactivity is not a uniform finding, a number of methodological challenges could explain discrepancies. As most studies utilize fMRI to measure blood-oxygen-level dependent signal, excess baseline activity could result in null findings due to subtraction analysis. Furthermore, heterogenous study design could mask consistent hyperactivity to specific stimuli. Regardless of directionality of amygdala abnormalities, as the amygdala plays a central role in emotional systems, these findings support dysfunctional emotional circuits in bipolar. A general reduction in ventrolateral prefrontal cortex activity is observed in bipolar, and is lateralised with regard to mood (i.e. left-depression, right-mania), and may underlie amygdala abnormalities. The dorsal ACC is commonly under-activated in bipolar, and is generally implicated in cognitive functions, while the ventral ACC is hyperactived and implicated in emotional functions. Combined, these abnormalities support the prefrontal-striatal-pallidial-thalamic limbic network underlying dysfunction in emotional regulation in bipolar disorder. Strakowski, along with DelBello and Adler have put forward a model of “anterior limbic” dysfunction in bipolar disorder in a number of papers.
In 2007, Green and colleagues suggested a model of bipolar disorder based on the convergence of cognitive and emotional processing on certain structures. For example, the dACC and sgACC were cognitively associated with impairment of inhibition of emotional responses and self monitoring, which could translate to emotional stimuli having excessive impact on mood. Deficits in working memory associated with abnormal dlPFC function could also translate to impaired ability to represent emotional stimuli, and therefore the impaired ability to reappraise emotional stimuli. Dysfunction in the amygdala and striatum has been associated with attentional biases, and may represent a bottom up mechanism of dysfunctional emotional processing.
Blond et al. proposed a model centred on dysfunction in an “amygdala-anterior paralimbic” system. This model was based on the consistent functional and structural abnormalities in the ventral prefrontal cortex and amygdala. The model also proposes a developmental component of bipolar disorder, wherein limbic abnormalities are present early on, but rostral prefrontal abnormalities develop later in the course. The importance of limbic dysfunction early in development is highlighted by the observation that amygdala lesions early in adulthood produce emotional abnormalities that are not present in people who develop amygdala damage in adulthood.
Lateralised seizure sequelae similar to bipolar has been reported in people with mesial temporal lobe seizures, and provides support for kindling hypotheses about bipolar. This observation led to the first experiments with anticonvulsants in bipolar, which are effective in stabilising mood. Studies reporting reduced markers of inhibitory interneurons post-mortem link the analogy with epilepsy to a possible reduction in inhibitory activity in emotional circuits. Overlap with epilepsy extends to include abnormalities in intracellular signalling, biochemistry in the hippocampus and prefrontal cortex, and structure and function of the amygdala.
The phenomenology and neuroanatomy of mania secondary to neurological disorders is consistent with findings in primary mania and bipolar disorder. While the diversity of lesions and difficulty in ruling out premorbid psychiatric conditions limit the conclusions that can be drawn, a number of findings are fairly consistent. Structurally, secondary mania is associated with destructive lesions that tend to occur in the right hemisphere, particularly the frontal cortex, mesial temporal lobe and basal ganglia. Functionally hyperactivity in the left basal ganglia and subcortical structures, and hypoactivity in the right ventral prefrontal and basotemporal cortex have been reported in cases of secondary mania. The destruction of right hemisphere or frontal areas is hypothesized to lead to a shift to excessive left sided or subcortical reward processing.
John O. Brooks III put forward a model of bipolar disorder involving dysregulation of a circuit called the “corticolimbic system”. The model was based on more or less consistent observations of reduced activity in the mOFC, vlPFC, and dlPFC, as well as the more or less consistent observations of increased activity in the amygdala, parahippocampal gyrus, cerebellar vermis, anterior temporal cortex, sgACC, and ACC. This pattern of abnormal activity was suggested to contribute to disrupted cognitive and affective processes in bipolar disorder.
Neurocognition
During acute mood episodes, people with bipolar demonstrate mood congruent processing biases. Depressed patients are quicker to react to negatively valenced stimuli, while manic patients are quicker to react to positively valenced stimuli. Acute mood episodes are also associated with congruent abnormalities during decision making tasks. Depressed bipolar is associated with conservative responding, while manic bipolar is associated with liberal responses. Both depression and mania are associated with similar and broad cognitive impairments, including on tests of attention, processing speed, working memory, executive functions, and reaction time.
Clinically, mania is characterised by spending sprees, poor judgement, and inappropriate speech and behaviour. Congruent with this, mania is associated impulsivity on Go-No Go tasks, deficits in emotional decision making, poor probabilistic reasoning, impaired ability on continuous performance tasks, set shifting, and planning. The clinical phenomenology and neurocognitive deficits are similar to those seen in patients with damage to the orbitofrontal cortex (OFC), which has been reported in functional neuroimaging studies to be abnormal in bipolar mania. Specifically, reduced blood flow to the lateral OFC has been reported, and may reflect dysfunction that leads to the neurocognitive deficits.
In novel environments, both bipolar manic and bipolar euthymic people demonstrate increased activity, exploration and linear movement that is greater than controls, people with ADHD and people with schizophrenia. Using this behavioural pattern in “reverse translational” studies, this behavioural abnormality has been associated with the cholinergic-aminergic hypothesis, which postulates elevated dopaminergic signalling in mania. Reducing the function of DAT using pharmacological or genetic means produces a similar behavioural pattern in animal models. Pharmacological data is consistent with dysfunction of dopamine in bipolar as some studies have reported hypersensitivity to stimulants (however, some studies have found that stimulants effectively attenuate manic behaviour, and co-morbid ADHD and bipolar are effectively treated with stimulants), and the mechanism of antimanic drugs may involve attenuating dopamine signalling.
Hypersensitivity of reward systems is consistent across mood states in bipolar, and is evident in the prodrome. Increases in goal directed behaviour, risk taking, positive emotions in response to reward, ambitious goal setting and inflexibility in goal directed behaviours are present in euthymia. Neuroimaging studies are consistent with trait hypersensitivity in reward systems, as both mania and depression is associated with elevated resting activity in the striatum, and elevated activity in the striatum and OFC during emotional processing, receipt of reward, and anticipation of reward. Increased activity in the striatum and OFC has also been reported in euthymia during anticipation and receipt of reward, although this finding is extremely inconsistent. These abnormalities may be related to circadian rhythm dysfunction in bipolar, including increased sleep latency, evening preference and poor sleep quality, as the neural systems responsible for both processes are functionally linked. A few lines of evidence suggest that elevated dopamine signalling, possibly due to reduced functionality in DAT, underlie abnormalities in reward function. Dopaminergic drugs such as L-DOPA can precipitate mania, and drugs that attenuate dopaminergic signalling extracellularly (antipsychotics) and intracellularly (lithium) can be efficacious in treating mania. While a large body of translational evidence exists to support DAT hypofunction, in vivo evidence is limited to one study reporting reduced DAT binding in the caudate.
Neuroimaging
Structural
In a review of structural neuroimaging in bipolar disorder, Strakowski proposed dysfunction in an iterative emotional network called the “anterior limbic network”, composed of the thalamus, globus pallidus, striatum, vlPFC, vmPFC, ACC, amygdala, dlPFC, and cerebellar vermis. Structural imaging studies frequently find abnormalities in these regions which are putatively involved in emotional and cognitive functions that are disrupted in bipolar disorder. For example, while structural neuroimaging studies do not always find abnormal PFC volume in bipolar disorder, when they do, PFC volume is reduced. Furthermore, reduced PFC volume is associated with response inhibition deficits and duration of illness. When the PFC at large is not examined and the focus is narrowed to the OFC/vPFC, results more consistently observed reductions, although not in bipolar youth. The sgACC volume is observed to be reduced not only in bipolar disorder, but also in unipolar disorder, as well as people with a family history of affective disorders. Enlargement of the striatum and globus pallidus are commonly found, and although some studies fail to observe this, at least one study has reported no volumetric but subtle morphometric abnormalities.
Structural neuroimaging studies consistently report increased frequency of white matter hyperintensities in people with bipolar. However, whether or not the lesions play a causative role is unknown. It is possible that they are a result of secondary factors, such as the processes underlying an increased risk of cardiovascular disease in bipolar. On the other hand, the observation of reduced white matter integrity in frontal-subcortical regions makes it possible that these hyperintensities play a role dysfunction between limbic and cortical regions. Global brain volume and morphology are normal in bipolar. Regional deficits in volume have been reported in ventrolateral and dorsolateral prefrontal regions. Based on this, it has been suggested that reduced limbic regulation by prefrontal regions plays a role in bipolar. Findings related to the volume of the basal ganglia have been inconsistent.
In healthy controls, amygdala volume is inversely related to age. This relationship is reversed in bipolar disorder, and meta analyses have found reduced amygdala volume in paediatric bipolar disorder, and increased amygdala volume in adulthood. This is hypothesized to reflect abnormal development of amygdala, possibly involving impaired synaptic pruning, although this may reflect medication or compensatory effects; that is, these abnormalities may not be involved in the mechanism of bipolar, and may instead be a consequence.
A 2016 meta analysis reported that bipolar disorder was associated with grey matter reductions bilaterally in the ACC, vmPFC, and insula extending to the temporal lobe. When compared with grey matter reductions in unipolar depression, significant overlap occurred in the insular and medial prefrontal regions. Although unipolar depression was associated with reductions in the ventral most and dorsal most regions of the mPFC and bipolar with a region near the genu of the corpus callosum, the overlap was still statistically significant. Similar to the overlap with major depression, a significant overlap of bipolar disorder with schizophrenia in grey matter volume reduction occurs in the anterior cingulate cortex, medial prefrontal cortex, lateral prefrontal cortex and bilateral insula.
A 2010 meta analysis of differences in regional grey matter volume between controls and bipolar disorder reported reductions bilaterally in the inferior frontal cortex and insula, which extended more prominently in the right side to include the precentral gyrus, as well as grey matter reductions in the pregenual anterior cingulate cortex (BA24) and anterior cingulate cortex (BA32). One meta analysis reported enlargement of the lateral ventricles and globus pallidus, as well as reductions in hippocampus volume and cross sectional area of the corpus callosum. Another meta analysis reported a similar increase volumes of the globus pallidus and lateral ventricles, as well as increased amygdala volume relative to people with schizophrenia. Reductions have also been reported in the right inferior frontal gyrus, insula, pars triangularis, pars opercularis, and middle and superior temporal gyrus. Structural neuroimaging in people who are susceptible to bipolar disorder (i.e. have a number of relatives with bipolar disorder) have produced few consistent results. Consistent abnormalities in adult first degree relatives include larger insular cortex volumes, while offspring demonstrate increased right inferior frontal gyrus volumes.
The ENIGMA bipolar disorder working group reported cortical thinning in the left Pars opercularis (BA44-inferior frontal gyrus), left fusiform gyrus, left rostral middle frontal cortex, right inferior parietal cortex, along with an increase in the right entorhinal cortex. Duration of illness was associated with reductions bilaterally in the pericalcarine gyrus, left rostral anterior cingulate and right cuneus, along with increases in the right entorhinal cortex. Treatment with lithium was associated with increased cortical thickness bilaterally in the superior parietal gyrus, left paracentral gyrus, and left paracentral lobule. A history of psychosis was associated with reduced surface area in the right frontal pole. Another study on subcortical abnormalities by the same research group reported reductions in the hippocampus, amygdala, and thalamus, along with ventricular enlargement.
One meta analysis reported that when correcting for lithium treatment, which was associated with increased hippocampal volume, people with bipolar demonstrate reduced hippocampus volume.
White matter is reduced in the posterior corpus callosum, regions adjacent to the anterior cingulate, the left optic radiation, and right superior longitudinal tract, and increased in the cerebellum and lentiform nuclei.
Functional
Studies examining resting blood flow, or metabolism generally observed abnormalities dependent upon mood state. Bipolar depression is generally associated with dlPFC and mOFC hypometabolism. Less consistent associations include reduced temporal cortex metabolism, increased limbic metabolism and reduced ACC metabolism. Mania is also associated with dlPFC and OFC hypometabolism. Limbic hypermetabolism is more consistent than in bipolar depression, but the overall study quality is low due to limitations associated with neuroimaging in acutely manic patients. Another review reported that mania is generally associated with frontal/ventral hypoactivation, while depression is generally associated with the opposite. A degree of lateralization with regard to abnormalities has been reported, with mania being associated with the right hemisphere, and depression the left. Trait abnormalities in euthymic patients have been observed, including hypoactivity in the ventral prefrontal cortex, and hyperactivity in the amygdala.
During cognitive or emotional tasks, functional neuroimaging studies, consistently find hyperactivation of the basal ganglia, amygdala, and thalamus. Prefrontal abnormalities are less consistently reported, although hyperactivation in the ventral prefrontal cortex is a fairly consistent finding. Hyperactivity in the amygdala and hypoactivity in the medial and ventral prefrontal cortex during exposure to emotional stimuli has been interpreted as reflecting dysfunction in emotional regulation circuits. Increased effective connectivity between the amygdala and orbitofrontal cortex, and elevated striatal responsiveness during reward tasks have been interpreted as hyper-responsiveness in positive emotion and reward circuitry. The abnormal activity in these circuits has been observed in non-emotional tasks, and is congruent with changes in grey and white matter in these circuits. Neural response during reward tasks differentiates unipolar depression from bipolar depression, with the former being associated with reduced neural response and the latter being associated with elevated neural response. An ALE meta analysis of functional neuroimaging comparing adults and adolescents found a larger degree of hyperactivity in the inferior frontal gyrus and precuneus, as well as a larger degree of hypoactivity in the anterior cingulate cortex in adolescents relative to adults.
Regardless of mood state, during response inhibition tasks, people with bipolar disorder underactivate the right inferior frontal gyrus. Changes specific on euthymia include hyperactivations in the left superior temporal gyrus and hypoactivations in the basal ganglia, and changes specific to mania include hyperactivation in the basal ganglia. A meta analysis of fMRI studies reported underactivations in the inferior frontal gyrus and putamen and hyperactivation of the parahippocampus, hippocampus, and amygdala. State specific abnormalities were reported for mania and euthymia. During mania, hypoactivation was significant in the inferior frontal gyrus, while euthymia was associated with hypoactivation of the lingual gyrus and hyperactivation of the amygdala.
A meta analysis using region of interest (as opposed to statistical parametric mapping) analysis reported abnormalities across paradigms for euthymic, depressed, and manic subjects. In bipolar mania, reduced activity was reported in the superior, middle, and inferior frontal gyri, while increased activity was reported in the parahippocampal, superior temporal, middle temporal, and inferior temporal gyri. In bipolar depression, reduced activity was reported in the sgACC, ACC, and middle frontal gyrus. In euthymia, reduced activity was reported in the dlPFC, vlPFC, and ACC, while increased activity was reported in the amygdala. During studies examining response to emotional faces, both mania and euthymia were reported to be associated with elevated amygdala activity.
An activation likelihood estimate meta analysis of bipolar studies that used paradigms involving facial emotions reported a number of increases and decreases in activation compared to healthy controls. Elevated activity was reported in the parahippocampal gyrus, putamen, and pulvinar nuclei, while reduced activity was reported bilaterally in the inferior frontal gyrus. Compared to major depressive disorder, bipolar patients overactivated the vACC, pulvinar nucleus, and parahippocampus gyrus/amygdala to a greater degree, while underactivating the dACC. Bipolar subjects overactivated parahippocampus for both fearful and happy expressions, while the caudate and putamen were overactived for happiness and fear respectively. Bipolar subjects also underactivated the ACC for both fearful and happy expressions, while the IFG was underactivated for fearful expressions only. These results were interpreted as reflecting increased engagement with emotionally salient stimuli in bipolar disorder.
Specific symptoms have been linked to various neuroimaging abnormalities in bipolar disorder, as well as schizophrenia. Reality distortion, disorganisation, and psychomotor poverty have been linked to prefrontal, thalamic, and striatal regions in both schizophrenia and bipolar (Table below).
Symptom Dimension
Implicated Regions in Bipolar
Implicated Regions in Schizophrenia
Disorganisation
1. Hypofunction in the ventrolateral prefrontal cortex (vlPFC). 2. Hypofunction in the medial prefrontal cortex (mPFC)/ACC.
1. Hypofunction in the medial prefrontal cortex (mPFC). 2. Hypofunction in the dorsolateral prefrontal cortex (dlPFC). 3. Hypofunction in the cerebellum. 4. Hypofunction in the insula. 5. Hypofunction in the temporal cortex.
Reality Distortion
1. Functional abnormalities in prefrontal and thalamic regions.
1. Reduced grey matter in perisylvian and thalamic regions. 2. Hypofunction of the amygdala, mPFC and hippocampus/parahippocampus.
Psychomotor Poverty
1. Functional abnormalities in the vlPFC and ventral striatum.
1. Reduced grey matter in the vlPFC, mPFC and dlPFC. 2. Reduced grey matter in the striatum, thalamus, amygdala and temporal cortices.
Frontal Cortex
Different regions of the ACC have been studied in the literature, with the subgenual (sgACC) and rostral (rACC) parts being largely separated. Grey matter volume in the sgACC has been, albeit with some exceptions, found to be reduced in bipolar. Along with this, bipolar is associated with increased blood flow in the sgACC that normalises with treatment. Congruent with these abnormalities is a reduction in glial cells observed in post mortem studies, and reduced integrity of white matter possibly involving a hemispheric imbalance. Findings in the rACC are largely the same as the sgACC (reduced GM, increased metabolism), although more studies have been carried out on protein expression and neuronal morphology. The rACC demonstrates reduced expression NMDA, kainate and GABA related proteins. These findings may be compensating for increased glutaminergic afferents, evidenced by increased Glx in MRS studies. One VBM study reported reduced grey matter in the dACC. Inconsistent results have been found during functional neuroimaging of cognitive tasks, with both decreased and increased activation being observed. Decreased neuron volume and a congruent increase in neural density have been found in the dACC. Reduced expression of markers of neural connectivity have been reported (e.g. synaptophysin, GAP-43), which is congruent with the abnormal structural connectivity observed in the region.
The orbitofrontal cortex demonstrates reduced grey matter, functional activity, GAD67 mRNA, neuronal volume in layer I, and microstructural integrity in people with bipolar.
Although the role of acute mood states is unknown, grey matter volume is generally reported as reduced in the dlPFC, along with resting and task evoked functional signals. Signals of myelination and density of GABAegic neurons is also reduced in the dlPFC, particularly in layers II-V.
Neurochemistry
Magnetic Resonance Spectroscopy (MRS)
Increased combined glutamine and glutamate (Glx) have been observed globally, regardless of medication status. Increased Glx has been associated with reduced frontal mismatch negativity, interpreted as dysfunction in NMDA signalling. N-acetyl aspartate levels in the basal ganglia are reduced in bipolar disorder, and trends towards increased in the dorsolateral prefrontal cortex. NAA to creatine ratios are reduced in the hippocampus.
One review of magnetic resonance spectroscopy studies reported increased choline in the basal ganglia, and cingulate as well as a decreased in NAA in the dlPFC and hippocampus. State specific findings were reported to include elevated phosphomonoesters during acute mood states, and reduced inositol with treatment. Another review reported inositol abnormalities in the basal ganglia, and frontal, temporal and cingulate regions. The finding of a trend towards increased NAA concentrations in the dlPFC may be due to medication status, as treatment with lithium or valproate has been noted to lead to null findings, or even elevated levels of NAA in the frontal cortex. In unmedicated populations, reduced NAA consistently found in the prefrontal cortex, particularly the dlPFC.
Various hypotheses related to monoamines have been proposed. The biogenic amine hypothesis posits general dysregulation of monoamines underlies bipolar and affective disorders. The cholinergic aminergic balance hypothesis posits that an increased ratio of cholinergic activity relative to adrenergic signalling underlies depression, while increased adrenergic signalling relative to cholinergic signalling underlies mania. The permissive hypothesis suggests that serotonin is necessary but not sufficient for affective symptoms, and that reduced serotonergic tone is common to both depression and mania.
Studies of the binding potential of dopamine receptor D2 and dopamine transporter have been inconsistent but dopamine receptor D1’s binding potential has been observed to be decreased. Drugs that release dopamine produce effects similar to mania, leading some to hypothesize that mania involves increased catecholaminergic signalling. Dopamine has also been implicated through genetic “reverse translational” studies demonstrating an association between reduced DAT functionality and manic symptoms. The binding potential of muscarinic receptors are reduced in vivo during depression, as well as in post mortem studies, supporting the cholinergic aminergic balance hypothesis.
The role of monoamines in bipolar have been studied using neurotransmitter metabolites. Reduced concentration of homovanillic acid, the primary metabolite of dopamine, in the cerebrospinal fluid (CSF) of people with depression is consistently reported. This finding is related to psychomotor retardation and anhedonia. Furthermore, parkinson’s disease is associated with high rates of depression, and one case study has reported the abolishment of parkinson’s symptoms during manic episodes. The binding potential of VMAT2 is also elevated in bipolar I patients with a history of psychosis, although this finding is inconsistent with finding that valproate increases VMAT2 expression in rodents. One study on DAT binding in acutely depressed people with bipolar reported reductions in the caudate but not putamen.
Studies of serotonin’s primary metabolite 5-HIAA have been inconsistent, although limited evidence points towards reduced central serotonin signalling in a subgroup of aggressive or suicidal patients. Studies assessing the binding potential of the serotonin transporter or serotonin receptors have also been inconsistent, but generally point towards abnormal serotonin signalling. One study reported both increased SERT binding in the insula, mPFC, ACC and thalamus, and decreased SERT binding in the raphe nuclei in acutely depressed bipolar. Serotonin may play a role in mania by increasing the salience of stimuli related to reward.
One more line of evidence that suggests a role of monoamines in bipolar is the process of antidepressant related affective switches. Selective serotonin reuptake inhibitors and more frequently, tricyclic antidepressants (TCAs) are associated with between a 10%-70% risk of affective switch from depression to mania or hypomania, depending upon the criteria used. The more robust association between TCAs and affective switches, as opposed to more selective drugs, has been interpreted as indicating that more extensive perturbation in monoamine systems is associated with more frequent mood switching.
Hypothalamic Pituitary Adrenal Axis
Bipolar disorder is associated with elevated basal and dexamethasone elicited cortisol and adrenocorticotropic hormone (ACTH). These abnormalities are particularly prominent in mania, and are inversely associated with antipsychotic use. The incidence of psychiatric symptoms associated with corticosteroids is between 6% and 32%. Corticosteroids may precipitate mania, supporting the role of the HPA axis in affective episodes. Measures from urinary versus salivary cortisol have been contradictory, with one study of the former concluding that HPA hyperactivity was a trait marker, while a study of the latter concluded that no difference in HPA activity exists in remission. Measurement during the morning are thought to be more sensitive due to the cortisol awakening response. Studies are generally more consistent, and observe HPA hyperactivity.
Neurotrophic Factors
Brain derived neurotrophic factor levels are peripherally reduced in both manic and depressive phases.
Intracellular Signalling
The levels of Gαs but not other G proteins is increased in the frontal, temporal and occipital cortices. The binding of serotonin receptors to G proteins is also elevated globally. Leukocyte and platelet levels of Gαs and Gαi is also elevated in those with bipolar disorder. Downstream targets of G protein signalling is also altered in bipolar disorder. Increased levels of adenylyl cyclase, protein kinase A (PKA), and cyclic adenosine monophosphate induced PKA activity are also reported. Phosphoinositide signalling is also altered, with elevated levels of phospholipase C, protein kinase C, and Gαq being reported in bipolar. Elevated cAMP stimulated phosphorylation or Rap1 (a substrate of PKA), along with increased levels of Rap1 have been reported in peripherally collected cells of people with bipolar. Increased coupling of serotonin receptors to G proteins has been observed. While linkage studies performed on genes related to G protein signalling, as well as studies on post mortem mRNA concentration fail to report an association with bipolar disorder, the overall evidence suggests abnormal coupling of neurotransmission systems with G proteins.
Mania may be specifically associated with protein kinase C hyperactivity, although most evidence for this mechanism is indirect. The gene DGKH has been reported in genome wide association studies to be related to bipolar disorder, and it is known to be involved in PKC regulation. Manipulation of PKC in animals produces behavioural phenotypes similar to mania, and PKC inhibition is a plausible mechanism of action for mood stabilisers. Overactive PKC signalling may lead to long term structural changes in the frontal cortex as well, potentially leading to progression of manic symptoms.
Glycogen synthase kinase 3 has been implicated in bipolar disorder, as bipolar medications lithium and valproate have been shown to increase its phosphorylation, thereby inhibiting it. However, some postmortem studies have not shown any differences in GSK-3 levels or the levels of a downstream target β-catenin. In contrast, one review reported a number of studies observing reduced expression of β-catenin and GSK3 mRNA in the prefrontal and temporal cortex.
Excessive response of arachidonic acid signalling cascades in response to stimulation by dopamine receptor D2 or NMDA receptors may be involved in bipolar mania. The evidence for this is primarily pharmacological, based on the observation that drugs that are effective in treating bipolar reduced AA cascade magnitude, while drugs that exacerbate bipolar do the opposite.
Calcium homeostasis may be impaired across all mood states. Elevated basal intracellular, and provoked calcium concentrations in platelets and transformed lymphoblasts are found in people with bipolar. Serum concentrations of calcium are also elevated, and abnormal calcium concentrations in response to stimulation of olfactory neurons is also observed. These findings are congruent with the genetic association of bipolar with CACNAC1, an L-type calcium channel, as well as the efficacy of anti-epileptic agents. Normal platelets placed in plasma from people with bipolar disorder do not demonstrate elevated levels of intracellular calcium, indicating that dysfunction lies intracellularly. One possible mechanism is that elevated inositol triphosphate (IP3) caused by hyperactive neuronal calcium sensor 1 causes excessive calcium release. Serum levels of S100B (a calcium binding protein) are elevated in bipolar mania.
Mitochondrial Dysfunction
Some researchers have suggested bipolar disorder is a mitochondrial disease. Some cases of familial chronic progressive external ophthalmoplegia demonstrate increased rates of bipolar disorder before the onset of CPEO, and the higher rate of maternal inheritance patterns support this hypothesis. Downregulation of genes encoding for mitochondrial subunits, decreased concentration of phosphocreatine, decreased brain pH, and elevated lactate concentrations have also been reported. Mitochondrial dysfunction may be related to elevated levels of the lipid peroxidation marker thiobarbituric acid reactive substances, which are attenuated by lithium treatment.
Neuropathology
A number of abnormalities in GABAergic neurons have been reported in people with bipolar disorder. People with bipolar demonstrate reduced expression of GAD67 in CA3/CA2 subregion of the hippocampus. More extensive reductions of other indicators of GABA function have been reported in the CA4 and CA1. Abnormal expression of kainate receptors on GABAergic cells have been reported, with reductions in GRIK1 and GRIK2 mRNA in the CA2/CA3 being found in people with bipolar. Decreased levels of HCN channels have also been reported, which, along with abnormal glutamate signalling, could contribute to reduced GABAergic tone in the hippocampus.
The observation of increased Glx in the prefrontal cortex is congruent with the observation of reduced glial cell counts and prefrontal cortex volume, as glia play an important role in glutamate homeostasis. Although the number and quality of studies examining NMDA receptor subunits is poor, evidence for reduced NMDA signalling and reduced contribution from the NR2A subunit is consistent.
Decreased neuron density and soma size in the ACC and dlPFC has been observed. The dlPFC also demonstrates reduced glial density, a finding that is less consistent in the ACC. The reduction in cell volume may be due to early stage apoptosis, a mechanism that is supported by studies observing reduced anti-apoptotic gene expression in both peripheral cells and neurons, as well as the reduction in BDNF that is consistently found in bipolar. Reductions in cortical glia are not found across the whole cortex (e.g. somatosensory areas demonstrate normal glial density and counts), indicating that systematic dysfunction in glial cells is not likely; rather, abnormal functionality of connectivity in specific regions may result in abnormal glia, which may in turn exacerbate dysfunction.
Dendritic atrophy and loss of oligodendrocytes is found in the medial prefrontal cortex, and is possibly specific to GABAergic neurons.
Immune Dysfunction
Elevated levels of IL-6, C-reactive protein (CRP) and TNFα have been reported in bipolar. Levels of some (IL-6 and CRP) but not all (TNFα) may be reduced by treatment. Increases in IL-6 have been reported in mood episodes, regardless of polarity. Inflammation has been consistently reported in bipolar disorder, and the progressive nature lies in dysregulation of NF-κB.
The Child Mania Rating Scales (CMRS) is a 21-item diagnostic screening measure designed to identify symptoms of mania in children and adolescents aged 9-17 using diagnostic criteria from the DSM-IV, developed by Pavuluri and colleagues.
There is also a 10-item short form. The measure assesses the child’s mood and behaviour symptoms, asking parents or teachers to rate how often the symptoms have caused a problem for the youth in the past month. Clinical studies have found the CMRS to be reliable and valid when completed by parents in the assessment of children’s bipolar symptoms. The CMRS also can differentiate cases of paediatric bipolar disorder from those with ADHD or no disorder, as well as delineating bipolar subtypes. A meta-analysis comparing the different rating scales available found that the CMRS was one of the best performing scales in terms of telling cases with bipolar disorder apart from other clinical diagnoses. The CMRS has also been found to provide a reliable and valid assessment of symptoms longitudinally over the course of treatment. The combination of showing good reliability and validity across multiple samples and clinical settings, along with being free and brief to score, make the CMRS a promising tool, especially since most other checklists available for youths do not assess manic symptoms.
Background
The Child Mania Rating Scale (CMRS) was created as a complement already existing measures like the Altman Self-Rating Mania Scale and the Young Mania Rating Scale, which were formulated for adults. The purpose of the CMRS is to both assess the symptoms of mania in paediatric bipolar disorder, and to accurately discriminate the symptoms of mania from symptoms of ADHD. It is important that the CMRS accurately discriminate from symptoms of ADHD because core symptoms of adolescent Bipolar Disorder and ADHD are shared between the two disorders: hyperactivity, impulsivity, and distractibility. The CMRS was designed specifically for younger children who may or may not have the ability to accurately answer questions about their behaviour. As a result, the questionnaire is filled out by parents are/or caregivers who work with the children on a daily basis. Previous mania scales were designed for use by either the clinician or the patient. Therefore, the CMRS is unique in that it allows parents and caregivers to contribute information about their child’s symptoms. This is especially important in cases where the child may be too young to fill out the questionnaires themselves.
Historically, effective rating and diagnosis of mania has been limited. Though many mania scales have been tested on adult populations, the Young Mania Rating Scale (YMRS) – which was tested against the child version (CMRS) as standard measure for screening mania- is the only adult scale that has also been studied for validity and reliability in prepubertal children. Previous attempts include the Beigel Scale/Manic State Rating Scale (MSRS) and the Patterson Scale, which used nurse and clinician reports to rate levels of mania. Neither scale effectively and consistently captured levels of mania in patients. Other measures of paediatric mania are generally limited because they are completed by the clinician, introducing potential for bias, and because they lack the depth necessary to differentiate between patient-specific ways in which symptoms are presented. The CMRS Parent and Teacher versions attempt to address some of the limitations by including a checklist that can gather information about behaviour at home, school, and other settings, rather than focusing only on what a clinician could directly observe. One study examined the accuracy of a shortened version of the CMRS-P, which included only 10 items, and found that its accuracy was similar to the full scale.
Typically, the CMRS takes only 10-15 minutes to administer. The questions ask about behaviour-specific actions and tendencies the child may have exhibited within the past month. The parent rates the behaviour on a scale from 1 to 4, where 1=never/rarely, 2=sometimes, 3=often, and 4=very often. A clinician examines the total score and determines if the child has ADHD or Bipolar Disorder. If a diagnosis Bipolar Disorder is deemed to be appropriate, the clinician will also determine the sub-type.
Versions
There is a short version (10 items) of the CMRS called the Brief CMRS/Brief CMRS-P. The shorter version was created because a shorter version is preferred to longer assessments if the shorter gives similar accuracy, which it does. Additionally, there is a teacher’s version of the CMRS called the CMRS-Teacher (CMRS-T).
Reliability and Validity
Reliability
Table 1: Rubric for evaluating norms and reliability for the Child Mania Rating Scale.
Designed originally as a self-report scale; parent and youth report correlate about the same as cross-informant scores correlate in general.
Test-Retest Reliability
Adequate
r = .96 over 1 week. Data on test-retest reliability over longer periods are needed.
Repeatability
Not published
No published studies formally checking repeatability.
Construct validity analyses (Exploratory Factor Analysis and Confirmatory Factor Analysis) for the CMRS-P indicated that the scale is unidimensional. Internal consistency measured by Cronbach’s alpha was .96 in a sample consisting of ADHD, Bipolar, and healthy control participants. In a sample of participants with bipolar disorder, the cronbach’s alpha was 91. Additionally, it has the ability to accurately differentiate paediatric bipolar disorder from ADHD and healthy controls greater than 90% of the time.
The teacher version (CMRS-T) also has 21 items. The internal consistency, measured by Cronbach’s alpha, was .86. Correlations between the parent and teacher versions of the CMRS range from .23 to .27. The CMRS teacher version has not been shown to discriminate bipolar from nonbipolar cases at better than chance levels and is not recommended for use in clinical practice for diagnosing bipolar disorder in children.
Validity
Table 2: Evaluation of validity and utility for the Child Mania Rating Scale
Criterion
Rating (Adequate, Good, Excellent, Too Good)
Explanation
Content Validity
Excellent
Covers both DSM diagnostic symptoms and a range of associated features. Consistently distinguishes between PBP sub-types and comorbid disorders.
Construct Validity (e.g. Predictive, Concurrent, Convergent, and Discriminant Validity)
Excellent
Shows convergent validity with other symptom scales. Correlations between CMRS-P and other several clinician-rating scales intended to measure manic symptoms (e.g. Washington University Schedule for Affective Disorder and Schizophrenia mania module, the Schedule for Affective Disorders and Schizophrenia Mania Rating Scale, and the Young Mania Rating Scales) were excellent (.78 to .98).
Discriminative Validity
Excellent/Too Good
Preliminary studies show that CMRS scores discriminate cases with unipolar and bipolar mood disorders from other clinical disorders. AUCs of >.90 are quite high. Comparison to healthy controls might imply unrealistic performance when compared to realities of clinical practice.
Validity Generalisation
Adequate
Shown to be effective for ethnically representative samples. More research and multiple settings are needed to sufficiently determine generalization.
Treatment Sensitivity
Good
The CMRS-P has also been found to be sensitive in detecting symptom change over the course of treatment in multiple studies.
Clinical Utility
Excellent
Free (public domain), designed to be completed in 10-15 minutes, preliminary data are promising. Less research than some of the other contenders, but easier reading level than General Behaviour Inventory and more sensitive to treatment effects than Mood Disorder Questionnaire.
Development and History
The CMRS was developed as a shorter, reliable, and valid parent-report screening instrument for mania. The short form was derived from the CMRS 21 item scale which is the first original mania rating scale developed for children and adolescents. It was not developed from the Young Mania Rating Scale (YMRS) that was originally designed for adults, ‘Young’ being the name of the author than the fact that it was a scale for ‘young’ population. The YMRS was derived from the Parent-Young Mania Rating Scale (P-YMRS). This scale, developed from the YMRS, was created for use with adult inpatients. The items of the P-YMRS did not include the updated DSM-IV criteria for adolescent Bipolar Disorder, and it includes several items with poor factor loadings. Furthermore, the content is not developmentally appropriate for children, as many of the items require insight or appearance, which are irrelevant to young children. Another promising measure is the GBI as it has good psychometric properties. However, the GBI is lengthy and complicated and requires the child to have at least a 7th-grade reading ability. One of the most widely used measures of mania symptoms is the Kiddie Schedule for Affective Disorders and Schizophrenia mania section. However, this measure is extremely extensive and requires much clinical training to administer.
During the development of the CMRS, researchers found that reliable and more accurate diagnostic accuracy is found in parent reports in comparison to teacher reports or self-reports and that these other reports rarely added new information to the parent report. Furthermore, the areas under the curve (AUC) of parent-rated instruments reported modest to excellent validity. Based on the evidence, the developers of the CMRS chose to create a measure that relied mainly on parent report.
Other parent report measures have been used to screen for Paediatric Bipolar Disorder, but these measures were not developed to look specifically for mania. One such measure is the Child Behaviour Checklist (CBCL). The CBCL, in addition to providing markers of psychopathology, has been used to detect mania in children. However, on the CBCL, researchers saw a consistent pattern of elevated scores, especially on the following symptoms: aggressive behaviour, attention problems, delinquency, anxiety, and depression. This pattern may be due to the high comorbidity of ADHD, oppositional defiant disorder, conduct disorder, and anxiety disorders in children with paediatric Bipolar Disorder. And although the CBCL is a reliable and validated measure, low scores on the CBCL may only rule out mania – conversely, it would be erroneous to rule in mania using CBCL scores alone.
For these reasons, the CMRS was developed to accurately and reliably assess mania in paediatric Bipolar Disorder, and differentiate its symptoms from other disorders with high comorbidity with paediatric Bipolar Disorder.
Impact
Though there is no gold-standard screening tool for Paediatric Bipolar Disorder, the CMRS has been described as a promising and useful tool for such a purpose. For example, institutional protocols for diagnosing and evaluating Bipolar Disorder in children may use the CMRS as an initial screening tool to establish the need to further evaluation of mania symptoms. In addition, the parent version of the CMRS (the CMRS-P) has been used in research studies to detect changes in children’s mania symptoms due to pharmacotherapy or psychotherapy. The CMRS is the first measure specifically developed for the purpose of screening for Bipolar Disorder in children.[30] As such, it offers an alternative to broadband rating scales like the Child Behaviour Checklist, which has been used as a screening tool for Bipolar Disorder in children with mixed findings regarding its reliability.
Furthermore, the CMRS-P (both the brief and full versions) have shown to be effective in distinguishing between mania and ADHD. The brief version effectively retains characteristics of the original CMRS, allowing for wider application and longitudinal use. Psychometric studies of the CMRS has demonstrated that the measure has excellent reliability and validity. Internal consistency is excellent and the measure correlates with clinician-administered interview measures for diagnosing paediatric mania. The measure is also accurately able to differentiate symptoms of paediatric Bipolar Disorder from ADHD and healthy control groups more than 90% of the time. Furthermore, the use of the CMRS in pharmacological research suggests that this measure is sensitive to treatment over time, which means that you can use this measure to assess treatment effectiveness.
Limitations
The CMRS suffers from the same problems as other self-report inventories, in that scores can be easily exaggerated or minimised by the person completing them – in this case, the parent or teacher – in a phenomenon called the social desirability bias. Like all questionnaires, the way the instrument is administered can also influence the final score. If a person is asked to fill out the form in front of other people in a clinical environment, for instance, social expectations have been shown to elicit a different response compared to administration via a postal survey. The age of the youth also may matter. Although the Child Mania Rating Scale has been shown to be a valid and reliable measure of mania in children, one concern is that its validity might change as the youth becomes an adolescent, and parents or teachers have less influence and awareness about the youth’s behaviour outside of the home or school. Additionally, it is also unclear of the CMRS’s ability to assess the change in mania systems as a child cycles out of mania and into depression.
Use in Other Populations
While the CMRS has not been validated in other languages, the CBCL, YMRS, GBI, and KSADS all have. However, the CMRS has been tested and translated into Spanish. The CMRS is available in fourteen languages with back translation through native/bilingual speakers, though not tested in all languages.
A mixed affective state, formerly known as a mixed-manic or mixed episode, has been defined as a state wherein features unique to both depression and mania – such as episodes of despair, doubt, anguish, rage or homicidal ideation, suicidal ideation, splitting, racing thoughts, sensory overload, pressure of activity, and heightened irritability – occur either simultaneously or in very short succession.
Previously, the diagnostic criteria for both a manic and depressive episode had to be met in a consistent and sustained fashion, with symptoms enduring for at least a week (or any duration if psychiatric hospitalisation was required), thereby restricting the official acknowledgement of mixed affective states to only a minority of patients with bipolar I disorder. In current DSM-5 nomenclature, however, a “mixed episode” no longer stands as an episode of illness unto itself; rather, the symptomology specifier “with mixed features” can be applied to any major affective episode (manic, hypomanic, or depressive), meaning that they are now officially recognised in patients with, in addition to bipolar I disorder, bipolar II disorder and, by convention, major depressive disorder. A depressive mixed state in a patient, however, even in the absence of discrete periods of mania or hypomania, effectively rules out unipolar depression.
Diagnostic Criteria
As affirmed by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the symptomology specifier “with mixed features” can be applied to manic episodes of bipolar I disorder, hypomanic episodes of either bipolar I disorder or bipolar II disorder and depressive episodes of either bipolar disorder or major depressive disorder, with at least three concurrent features of the opposite polarity being present. As a result, the presence of “mixed features” are now recognised in patients with bipolar II disorder and major depression; as earlier noted, however, although it is customary to withhold a diagnosis of a bipolar disorder until a manic or hypomanic episode appears, the presence of such features in a depressed patient even with no history of discrete mania or hypomania is strongly suggestive of the disorder.
Nevertheless, the DSM-5’s narrower definition of mixed episodes may result in fewer patients meeting mixed criteria compared to DSM-IV. A call was made by Tohen in 2017 for introducing changes from a currently phenomenological to a target oriented approach to DSM-5 mixed mood criteria in order to achieve more personalized medical attention.
Two features of both mania or hypomania and depression may superficially overlap and even resemble each other, namely “an increase in goal-directed activity” (psychomotor acceleration) vs. psychomotor agitation and “flight of ideas” and “racing thoughts” vs. depressive rumination. Attending to the patient’s experiences is very important. In the psychomotor agitation commonly seen in depression, the “nervous energy” is always overshadowed by a strong sense of exhaustion and manifests as purposeless movements (e.g. pacing, hand-wringing); in psychomotor acceleration, however, the excess in movement stems from an abundance of energy and is often channelled and purposeful. Likewise, in depressive rumination, the patient experiences the repetitive thoughts as heavy, leaden, and plodding; in psychic acceleration, however, (as seen in mania or hypomania) the thoughts move in a rapid progression, with many themes, rather than a singular one, being touched upon. Even when such experiences are accounted for on the basis of depression, the possibility does still exist, however, that the depressive episode may be complicated by other manic or hypomanic symptoms, in which case it is often prudent to attend to the patient’s personal and family history (e.g. family history of bipolar disorder, early age of onset) to determine whether or not the patient has bipolar disorder.
Treatment
Treatment of mixed states is typically based upon administration of mood stabilising medication, which may include anticonvulsants such as valproic acid; atypical antipsychotics such as quetiapine, olanzapine, aripiprazole, and ziprasidone; or first-generation antipsychotics such as haloperidol. There is question of lithium’s efficacy for treatment of mixed states due to conflicting conclusions drawn from various trials and research. Mood stabilisers work to reduce the manic symptoms associated with the mixed state, but they are not considered particularly effective for improving concurrent depressive symptoms.
Bipolar II disorder is a bipolar spectrum disorder (refer to Bipolar I disorder) characterised by at least one episode of hypomania and at least one episode of major depression. Diagnosis for bipolar II disorder requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder.
Hypomania is a sustained state of elevated or irritable mood that is less severe than mania yet may still significantly affect quality of life and result in permanent consequences including reckless spending, damaged relationships and poor judegment. Unlike mania, hypomania is not associated with psychosis. The hypomanic episodes associated with bipolar II disorder must last for at least four days.
Commonly, depressive episodes are more frequent and more intense than hypomanic episodes. Additionally, when compared to bipolar I disorder, type II presents more frequent depressive episodes and shorter intervals of well-being. The course of bipolar II disorder is more chronic and consists of more frequent cycling than the course of bipolar I disorder. Finally, bipolar II is associated with a greater risk of suicidal thoughts and behaviours than bipolar I or unipolar depression. Although bipolar II is commonly perceived to be a milder form of Type I, this is not the case. Types I and II present equally severe burdens.
Bipolar II is notoriously difficult to diagnose. Patients usually seek help when they are in a depressed state, or when their hypomanic symptoms manifest themselves in unwanted effects, such as high levels of anxiety, or the seeming inability to focus on tasks. Because many of the symptoms of hypomania are often mistaken for high-functioning behaviour or simply attributed to personality, patients are typically not aware of their hypomanic symptoms. In addition, many people who suffer from Bipolar II have periods of normal affect. As a result, when patients seek help, they are very often unable to provide their doctor with all the information needed for an accurate assessment; these individuals are often misdiagnosed with unipolar depression. Bipolar II is more common than Bipolar I, while Bipolar II and major depressive disorder have about the same rate of diagnosis. Of all individuals initially diagnosed with major depressive disorder, between 40% and 50% will later be diagnosed with either BP-I or BP-II. Substance use disorders (which have high co-morbidity with BP-II) and periods of mixed depression may also make it more difficult to accurately identify BP-II. Despite the difficulties, it is important that BP-II individuals be correctly assessed so that they can receive the proper treatment. Antidepressant use, in the absence of mood stabilisers, is correlated with worsening BP-II symptoms.
Brief History
In 19th century psychiatry, mania covered a broad range of intensity, and hypomania was equated by some to concepts of ‘partial insanity’ or monomania. A more specific usage was advanced by the German neuro-psychiatrist Emanuel Ernst Mendel in 1881, who wrote “I recommend (taking under consideration the word used by Hippocrates) to name those types of mania that show a less severe phenomenological picture, ‘hypomania'”. Narrower operational definitions of hypomania were developed from the 1960s/1970s.
The first diagnostic distinction to be made between manic-depression involving mania, and that involving hypomania, came from Carl Gustav Jung in 1903. In his paper, Jung introduced the non-psychotic version of the illness with the introductory statement, “I would like to publish a number of cases whose peculiarity consists in chronic hypomanic behavior” where “it is not a question of real mania at all but of a hypomanic state which cannot be regarded as psychotic.” Jung illustrated the hypomanic variation with five case histories, each involving hypomanic behaviour, occasional bouts of depression, and mixed mood states, which involved personal and interpersonal upheaval for each patient.
In 1975, Jung’s original distinction between mania and hypomania gained support. Fieve and Dunner published an article recognizing that only individuals in a manic state require hospitalisation. It was proposed that the presentation of either the one state or the other differentiates two distinct diseases; the proposition was initially met with scepticism. However, studies since confirm that bipolar II is a “phenomenologically” distinct disorder.
Empirical evidence, combined with treatment considerations, led the DSM-IV Mood Disorders Work Group to add bipolar II disorder as its own entity in the 1994 publication. (Only one other mood disorder was added to this edition, indicating the conservative nature of the DSM-IV work group.) In May 2013, the DSM-5 was released. Two revisions to the existing Bipolar II criteria are anticipated. The first expected change will reduce the required duration of a hypomanic state from four to two days. The second change will allow hypomania to be diagnosed without the manifestation of elevated mood; that is, increased energy/activity will be sufficient. The rationale behind the latter revision is that some individuals with Bipolar II manifest only visible changes in energy. Without presenting elevated mood, these individuals are commonly misdiagnosed with major depressive disorder. Consequently, they receive prescriptions for antidepressants, which unaccompanied by mood stabilisers, may induce rapid cycling or mixed states.
Signs and Symptoms
Hypomanic Episodes
Hypomania is the signature characteristic of Bipolar II disorder. It is a state characterised by euphoria and/or an irritable mood. In order for an episode to qualify as hypomanic, the individual must also present three or more of the below symptoms, and last at least four consecutive days and be present most of the day, nearly every day.
Inflated self-esteem or grandiosity.
Decreased need for sleep (e.g. feels rested after only 3 hours of sleep).
More talkative than usual or pressure to keep talking.
Flight of ideas or subjective experience that thoughts are racing.
Distractability (i.e. attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.
Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).
It is important to distinguish between hypomania and mania. Mania is generally greater in severity and impairs function, sometimes leading to hospitalisation and in the most severe cases, psychosis. In contrast, hypomania usually increases functioning. For this reason, it is not uncommon for hypomania to go unnoticed. Often it is not until individuals are in a depressive episode that they seek treatment, and even then their history of hypomania may go undiagnosed. Although hypomania may increase functioning, episodes need to be treated because they may precipitate a depressive episode.
Depressive Episodes
It is during depressive episodes that BP-II patients often seek help. Symptoms may be syndromal or subsyndromal. Depressive BP-II symptoms may include five or more of the below symptoms (at least one of them must be either depressed mood or loss of interest/pleasure). In order to be diagnosed, they need to be present only during the same two-week period, as a change from previous hypomanic functioning:
Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g. feels sad, empty, or hopeless) or observation made by others (e.g. appears tearful). In children and adolescents, this could be irritable mood.
Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).
Significant weight loss when not dieting or weight gain (e.g. a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day (e.g. in children, failure to make expected weight gain).
Insomnia or hypersomnia nearly every day.
Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).
Fatigue or loss of energy nearly every day.
Feelings of worthlessness or excessive or inappropriate guilt nearly every day (not merely self-reproach or guilt about being sick).
Diminished ability to think or concentrate, possible irritability or indecisiveness, nearly every day (either by subjective account or as observed by others).
Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for completing suicide.
Evidence also suggests that BP-II is strongly associated with atypical depression. Essentially, this means that many BP-II patients exhibit reverse vegetative symptoms. BP-II patients may have a tendency to oversleep and overeat, while typically depressed patients sleep and eat less than usual.
Mixed Depression
Depressive mixed states occur when patients experience depression and non-euphoric, usually subsyndromal, hypomania at the same time. As mentioned previously, it is particularly difficult to diagnose BP-II when a patient is in this state.
In a mixed state, mood is depressed, but the following symptoms of hypomania present as well:
Irritability.
Mental hyperactivity.
Behavioural hyperactivity.
Mixed states are associated with greater levels of suicidality than non-mixed depression. Antidepressants may increase this risk.
Relapse
In the case of a relapse, the following symptoms often occur and are considered early warning signs:
Sleep disturbance: patient requires less sleep and does not feel tired.
Racing thoughts and/or speech.
Anxiety.
Irritability.
Emotional intensity.
Spending more money than usual.
Binge behaviour, including food, drugs, or alcohol.
Arguments with family members and friends.
Taking on many projects at once.
People with bipolar disorder may develop dissociation to match each mood they experience. For some, this is done intentionally, as a means by which to escape trauma or pain from a depressive period, or simply to better organise one’s life by setting boundaries for one’s perceptions and behaviours.
Studies indicate that the following events may also precipitate relapse in BP-II patients:
Stressful life events.
Relatives’ or peers’ criticism.
Antidepressant use.
Disrupted circadian rhythm.
Comorbid Conditions
Comorbid conditions are extremely common in individuals with BP-II. In fact, individuals are twice as likely to present a comorbid disorder than not. These include anxiety, eating, personality (cluster B), and substance use disorders. For bipolar II disorder, the most conservative estimate of lifetime prevalence of alcohol or other substance use disorders is 20%. In patients with comorbid substance use disorder and BP-II, episodes have a longer duration and treatment compliance decreases. Preliminary studies suggest that comorbid substance use is also linked to increased risk of suicidality. The question of which condition should be designated the index and which the comorbid condition is not self-evident and may vary in relation to the research question, the disease that prompted a particular episode of care, or of the specialty of the attending physician. A related notion is that of complication, a condition that coexists or ensues, as defined in the Medical Subject Headings (MeSH)-controlled vocabulary maintained by the National Library of Medicine (NLM).
Causes
Scientists are studying the possible causes of bipolar disorder and most agree that there is no single cause. There have been very few studies conducted to examine the possible causes of Bipolar II. Those that have been done have not considered Bipolar I and Bipolar II separately and have had inconclusive results. Researchers have found that patients with either Bipolar I or II may have increased levels of blood calcium concentrations, but the results are inconclusive. The studies that have been conducted did not find a significant difference between those with Bipolar I or Bipolar II. There has been a study looking at genetics of Bipolar II disorder and the results are inconclusive; however, scientists did find that relatives of people with Bipolar II are more likely to develop the same bipolar disorder or major depression rather than developing Bipolar I disorder. The cause of Bipolar disorder can be attributed to misfiring neurotransmitters that overstimulate the amygdala, which in turn causes the prefrontal cortex to stop working properly. The bipolar patient becomes overwhelmed with emotional stimulation with no way of understanding it, which can trigger mania and exacerbate the effects of depression.
Diagnosis
A person diagnosed with bipolar II disorder will have experienced at least one hypomanic episode, no manic episode, and one or more major depressive episodes. Although bipolar II is thought to be less severe than bipolar I in regards to symptom intensity, it is actually more severe and distressing with respect to episode frequency and overall course. Those with bipolar II often experience more frequent bouts of depressive episodes. Specific criteria defined by the DSM-5 for a bipolar II diagnosis:
Criteria have been met for at least one hypomanic episode and at least one major depressive episode.
There has never been a manic episode.
The occurrence of the hypomanic episode(s) and major depressive episode(s) is not better explained by schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.
Causes significant stress or impairment in social, occupational, or other important areas of functioning.
Studies have identified major differences between bipolar I and bipolar II in regards to their clinical features, comorbidity rates and family histories. According to Baek et al. (2011), during depressive episodes, bipolar II patients tend to show higher rates of psychomotor agitation, guilt, shame, suicidal ideation, and suicide attempts. Bipolar II patients have shown higher lifetime comorbidity rates of DSM axis I diagnoses such as phobias, anxiety disorders, substance & alcohol use, and eating disorders and there is a higher correlation between bipolar II patients and family history of psychiatric illness, including major depression and substance-related disorders. The occurrence rate of psychiatric illness in first degree relatives of bipolar II patients was 26.5%, versus 15.4% in bipolar I patients.
Screening instruments like the Mood Disorders Questionnaire (MDQ) are helpful tools in determining a patient’s status on the bipolar spectrum, and getting families involved can also improve chances of an accurate diagnosis and acknowledgment of hypomanic episodes. In addition, there are certain features that have been shown to increase the chances that depressed patients are suffering from a bipolar disorder including atypical symptoms of depression like hypersomnia and hyperphagia, a family history of bipolar disorder, medication-induced hypomania, recurrent or psychotic depression, antidepressant refractory depression, and early or postpartum depression.
Specifiers
Chronic.
With Anxious Distress (DSM-5).
With catatonic features.
With melancholic features.
With psychotic features.
With atypical features.
With postpartum onset.
Longitudinal course specifiers (with and without inter-episode recovery).
With seasonal pattern (applies only to the pattern of major depressive episodes).
With rapid cycling.
Treatments
Treatment typically includes three things: the treatment of acute hypomania, the treatment of acute depression, and the prevention of the relapse of either hypomania or depression. The main goal is to make sure that patients do not harm themselves.
Medications
The most common treatment for reducing bipolar II disorder symptoms is medication, usually in the form of mood stabilisers. However, treatment with mood stabilisers may produce a flat affect in the patient, which is dose-dependent. Concurrent use of SSRI antidepressants may help some with bipolar II disorder, though these medications should be used with caution because it is believed that they may cause a hypomanic switch.
The pharmaceutical management of bipolar II disorder is not generally supported by strong evidence, with limited randomised controlled trials (RCTs) published in the literature. Some medications used are:
Lithium: There is strong evidence that lithium is effective in treating both the depressive and hypomanic symptoms in bipolar II. In addition, its action as a mood stabiliser can be used to decrease the risk of hypomanic switch in patients treated with antidepressants.
Anticonvulsants: There is evidence that lamotrigine decreases the risk of relapse in rapid-cycling bipolar II. It appears to be more effective in bipolar II than bipolar I, suggesting that lamotrigine is more effective for the treatment of depressive rather than manic episodes. Doses ranging from 100-200 mg have been reported to have the most efficacy, while experimental doses of 400 mg have rendered little response. A large, multicentre trial comparing carbamazepine and lithium over two and a half years found that carbamazepine was superior in terms of preventing future episodes of bipolar II, although lithium was superior in individuals with bipolar I. There is also some evidence for the use of valproate and topiramate, although the results for the use of gabapentin have been disappointing.
Antidepressants: There is evidence to support the use of SSRI and SNRI antidepressants in bipolar II. Some sources consider them to be one of the first-line treatments. However, antidepressants also pose significant risks, including a switch to mania, rapid cycling, and dysphoria, so many psychiatrists advise against their use for bipolar. When used, antidepressants are typically combined with a mood stabiliser.
Antipsychotics: There is good evidence for the use of quetiapine, which has been shown to help to prevent recurrence in mania and depression, and it has been approved by the US Food and Drug Administration (FDA) for this indication. There is also some evidence for the use of risperidone, although the relevant trial was not placebo-controlled and was complicated by the use of other medications in some of the patients.
Dopamine agonists: There is evidence for the efficacy of pramipexole from one RCT.
Non-Pharmaceutical Therapies
Non-pharmaceutical therapies can also help those with the illness. These include:
Relapse can still occur, despite continued medication and therapy.
Prognosis
There is evidence to suggest that bipolar II has a more chronic course of illness than bipolar I disorder. This constant and pervasive course of the illness leads to an increased risk in suicide and more hypomanic and major depressive episodes with shorter periods between episodes than bipolar I patients experience. The natural course of bipolar II disorder, when left untreated, leads to patients spending the majority of their lives unwell with much of their suffering stemming from depression. Their recurrent depression results in personal suffering and disability.
This disability can present itself in the form of psychosocial impairment, which has been suggested to be worse in bipolar II patients than in bipolar I patients. Another facet of this illness that is associated with a poorer prognosis is rapid cycling, which denotes the occurrence of four or more major depressive, hypomanic, and/or mixed episodes in a 12-month period. Rapid cycling is quite common in those with Bipolar II, much more so in women than in men (70% vs. 40%), and without treatment leads to added sources of disability and an increased risk of suicide. Women are more prone to rapid cycling between hypomanic episodes and depressive episodes. To improve a patient’s prognosis, long-term therapy is most favourably recommended for controlling symptoms, maintaining remission and preventing relapses. With treatment, patients have been shown to present a decreased risk of suicide (especially when treated with lithium) and a reduction of frequency and severity of their episodes, which in turn moves them toward a stable life and reduces the time they spend ill. To maintain their state of balance, therapy is often continued indefinitely, as around 50% of the patients who discontinue it relapse quickly and experience either full-blown episodes or sub-syndromal symptoms that bring significant functional impairments.
Functioning
The deficits in functioning associated with Bipolar II disorder stem mostly from the recurrent depression that Bipolar II patients suffer from. Depressive symptoms are much more disabling than hypomanic symptoms and are potentially as, or more disabling than mania symptoms. Functional impairment has been shown to be directly linked with increasing percentages of depressive symptoms, and because sub-syndromal symptoms are more common – and frequent – in Bipolar II disorder, they have been implicated heavily as a major cause of psychosocial disability. There is evidence that shows the mild depressive symptoms, or even sub-syndromal symptoms, are responsible for the non-recovery of social functioning, which furthers the idea that residual depressive symptoms are detrimental for functional recovery in patients being treated for Bipolar II. It has been suggested that symptom interference in relation to social and interpersonal relationships in Bipolar II Disorder is worse than symptom interference in other chronic medical illnesses such as cancer. This social impairment can last for years, even after treatment that has resulted in a resolution of mood symptoms.
The factors related to this persistent social impairment are residual depressive symptoms, limited illness insight (a very common occurrence in patients with Bipolar II Disorder), and impaired executive functioning. Impaired ability in regards to executive functions is directly tied to poor psychosocial functioning, a common side-effect in patients with Bipolar II.
The impact on a patient’s psychosocial functioning stems from the depressive symptoms (more common in Bipolar II than Bipolar I). An increase in these symptoms’ severity seems to correlate with a significant increase in psychosocial disability. Psychosocial disability can present itself in poor semantic memory, which in turn affects other cognitive domains like verbal memory and (as mentioned earlier) executive functioning leading to a direct and persisting impact on psychosocial functioning.
An abnormal semantic memory organization can manipulate thoughts and lead to the formation of delusions and possibly affect speech and communication problems, which can lead to interpersonal issues. Bipolar II patients have also been shown to present worse cognitive functioning than those patients with Bipolar I, though they demonstrate about the same disability when it comes to occupational functioning, interpersonal relationships, and autonomy. This disruption in cognitive functioning takes a toll on their ability to function in the workplace, which leads to high rates of work loss in Bipolar II patient populations. After treatment and while in remission, Bipolar II patients tend to report a good psychosocial functioning but they still score less than patients without the disorder. These lasting impacts further suggest that a prolonged exposure to an untreated Bipolar II disorder can lead to permanent adverse effects on functioning.
Recovery and Recurrence
Bipolar II Disorder has a chronic relapsing nature. It has been suggested that Bipolar II patients have a higher degree of relapse than Bipolar I patients. Generally, within four years of an episode, around 60% of patients will relapse into another episode. Some patients are symptomatic half the time, either with full on episodes or symptoms that fall just below the threshold of an episode.
Because of the nature of the illness, long-term therapy is the best option and aims to not only control the symptoms but to maintain sustained remission and prevent relapses from occurring. Even with treatment, patients do not always regain full functioning, especially in the social realm. There is a very clear gap between symptomatic recovery and full functional recovery for both Bipolar I and Bipolar II patients. As such, and because those with Bipolar II spend more time with depressive symptoms that do not quite qualify as a major depressive episode, the best chance for recovery is to have therapeutic interventions that focus on the residual depressive symptoms and to aim for improvement in psychosocial and cognitive functioning. Even with treatment, a certain amount of responsibility is placed in the patient’s hands; they have to be able to assume responsibility for their illness by accepting their diagnosis, taking the required medication, and seeking help when needed to do well in the future.
Treatment often lasts after remission is achieved, and the treatment that worked is continued during the continuation phase (lasting anywhere from 6-12 months) and maintenance can last 1-2 years or, in some cases, indefinitely. One of the treatments of choice is Lithium, which has been shown to be very beneficial in reducing the frequency and severity of depressive episodes. Lithium prevents mood relapse and works especially well in Bipolar II patients who experience rapid-cycling. Almost all Bipolar II patients who take lithium have a decrease in the amount of time they spend ill and a decrease in mood episodes.
Along with medication, other forms of therapy have been shown to be beneficial for Bipolar II patients. A treatment called a “well-being plan” serves several purposes: it informs the patients, protects them from future episodes, teaches them to add value to their life, and works toward building a strong sense of self to fend off depression and reduce the desire to succumb to the seductive hypomanic highs. The plan has to aim high. Otherwise, patients will relapse into depression. A large part of this plan involves the patient being very aware of warning signs and stress triggers so that they take an active role in their recovery and prevention of relapse.
Mortality
Several studies have shown that the risk of suicide is higher in patients who suffer from Bipolar II than those who suffer from Bipolar I, and especially higher than patients who suffer from major depressive disorder.
In results of a summary of several lifetime study experiments, it was found that 24% of Bipolar II patients experienced suicidal ideation or suicide attempts compared to 17% in Bipolar I patients and 12% in major depressive patients. Bipolar disorders, in general, are the third leading cause of death in 15 to 24 year olds. Bipolar II patients were also found to employ more lethal means and have more complete suicides overall.
Bipolar II patients have several risk factors that increase their risk of suicide. The illness is very recurrent and results in severe disabilities, interpersonal relationship problems, barriers to academic, financial, and vocational goals, and a loss of social standing in their community, all of which increase the likelihood of suicide. Mixed symptoms and rapid-cycling, both very common in Bipolar II, are also associated with an increased risk of suicide. The tendency for Bipolar II to be misdiagnosed and treated ineffectively, or not at all in some cases, leads to an increased risk.
As a result of the high suicide risk for this group, reducing the risk and preventing attempts remains a main part of the treatment; a combination of self-monitoring, close supervision by a therapist, and faithful adherence to their medication regimen will help to reduce the risk and prevent the likelihood of suicide.
Suicide, which is both a stereotypic yet highly individualised act, is a common endpoint for many patients with severe psychiatric illness. The mood disorders (depression and bipolar manic-depression) are by far the most common psychiatric conditions associated with suicide. At least 25% to 50% of patients with bipolar disorder also attempt suicide at least once. With the exception of lithium – which is the most demonstrably effective treatment against suicide – remarkably little is known about specific contributions of mood-altering treatments to minimising mortality rates in persons with major mood disorders in general and bipolar depression in particular. Suicide is usually a manifestation of severe psychiatric distress that is often associated with a diagnosable and treatable form of depression or other mental illness. In a clinical setting, an assessment of suicidal risk must precede any attempt to treat psychiatric illness.
Society and Culture
Select list of people with bipolar disorder:
Heath Black revealed in his autobiography, Black, that he has been diagnosed with Bipolar II.
Maria Bamford has been diagnosed with Bipolar II.
Geoff Bullock, singer-songwriter, was diagnosed with Bipolar II.
Mariah Carey was diagnosed with Bipolar II in 2001. In 2018, publicly revealed and actively seeking treatment in the form of therapy and medication.
Charmaine Dragun, former Australian journalist/newsreader. Inquest concluded she had Bipolar II.
Joe Gilgun has been diagnosed with Bipolar II.
Shane Hmiel has been diagnosed with Bipolar II.
Jesse Jackson Jr. has been diagnosed with Bipolar II.
Thomas Eagleton received a diagnosis of Bipolar II from Dr. Frederick K. Goodwin.
Carrie Fisher had been diagnosed with Bipolar II.
Albert Lasker is speculated to have had Bipolar II.
Demi Lovato has been diagnosed with Bipolar II.
Evan Perry, subject of the documentary Boy Interrupted, was diagnosed with Bipolar II.
Sylvia Plath is speculated to have had Bipolar II.
Richard Rossi, filmmaker, musician, and maverick minister was diagnosed with Bipolar II.
Rumer has been diagnosed with Bipolar II.
Robert Schumann is speculated to have had Bipolar II.
Catherine Zeta-Jones received treatment for Bipolar II disorder after dealing with the stress of her husband’s throat cancer. According to her publicist, Zeta-Jones made a decision to check into a “mental health facility” for a brief stay.
Bipolar I disorder (BD-I; pronounced “type one bipolar disorder”) is a type of bipolar spectrum disorder characterised by the occurrence of at least one manic episode, with or without mixed or psychotic features.
Most people also, at other times, have one or more depressive episodes, and all experience a hypomanic stage before progressing to full mania.
It is a type of bipolar disorder, and conforms to the classic concept of manic-depressive illness, which can include psychosis during mood episodes.
The essential feature of bipolar I disorder is a clinical course characterised by the occurrence of one or more manic episodes or mixed episodes. Often, individuals have had one or more major depressive episodes. One episode of mania is sufficient to make the diagnosis of bipolar disorder; the person may or may not have a history of major depressive disorder. Episodes of substance-induced mood disorder due to the direct effects of a medication, or other somatic treatments for depression, drug abuse, or toxin exposure, or of mood disorder due to a general medical condition need to be excluded before a diagnosis of bipolar I disorder can be made. Bipolar I disorder requires confirmation of only 1 full manic episode for diagnosis, but may be associated with hypomanic and depressive episodes as well. Diagnosis for bipolar II disorder does not include a full manic episode; instead, it requires the occurrence of both a hypomanic episode and a major depressive episode. Serious aggression has been reported to occur in one of every ten first-major episode BD-I patients with psychotic features, its prevalence in this group being particularly high in association with a recent suicide attempt, alcohol-abuse, learning disability, or manic polarity in the first episode.
Bipolar I disorder (and bipolar II disorder) is often comorbid with other disorders including PTSD, substance use disorders and a variety of mood disorders. Up to 40% of people with bipolar disorder also present with PTSD, with higher rates occurring in women and individuals with bipolar I disorder. In addition, the episodes must not be better accounted for by schizoaffective disorder or superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or a psychotic disorder not otherwise specified.
Medical Assessment
Regular medical assessments are performed to rule-out secondary causes of mania and depression. These tests include complete blood count, glucose, serum chemistry/electrolyte panel, thyroid function test, liver function test, renal function test, urinalysis, vitamin B12 and folate levels, HIV screening, syphilis screening, and pregnancy test, and when clinically indicated, an electrocardiogram (ECG), an electroencephalogram (EEG), a computed tomography (CT scan), and/or a magnetic resonance imagining (MRI) may be ordered. Drug screening includes recreational drugs, particularly synthetic cannabinoids, and exposure to toxins.
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR)
Dx Code #
Disorder
Description
296.0x
Bipolar I
Single manic episode
296.40
Bipolar I
Most recent episode hypomanic
296.4x
Bipolar I
Most recent episode manic
296.5x
Bipolar I
Most recent episode depressed
296.6x
Bipolar I
Most recent episode mixed
296.7
Bipolar I
Most recent episode unspecified
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
In May 2013, American Psychiatric Association released the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). There are several proposed revisions to occur in the diagnostic criteria of Bipolar I Disorder and its subtypes. For Bipolar I Disorder 296.40 (most recent episode hypomanic) and 296.4x (most recent episode manic), the proposed revision includes the following specifiers: with psychotic features, with mixed features, with catatonic features, with rapid cycling, with anxiety (mild to severe), with suicide risk severity, with seasonal pattern, and with postpartum onset. Bipolar I Disorder 296.5x (most recent episode depressed) will include all of the above specifiers plus the following: with melancholic features and with atypical features. The categories for specifiers will be removed in DSM-5 and criterion A will add or there are at least 3 symptoms of major depression of which one of the symptoms is depressed mood or anhedonia. For Bipolar I Disorder 296.7 (most recent episode unspecified), the listed specifiers will be removed.
The criteria for manic and hypomanic episodes in criteria A & B will be edited. Criterion A will include “and present most of the day, nearly every day”, and criterion B will include “and represent a noticeable change from usual behaviour”. These criteria as defined in the DSM-IV-TR have created confusion for clinicians and need to be more clearly defined.
There have also been proposed revisions to criterion B of the diagnostic criteria for a Hypomanic Episode, which is used to diagnose For Bipolar I Disorder 296.40, Most Recent Episode Hypomanic. Criterion B lists “inflated self-esteem, flight of ideas, distractibility, and decreased need for sleep” as symptoms of a Hypomanic Episode. This has been confusing in the field of child psychiatry because these symptoms closely overlap with symptoms of attention deficit hyperactivity disorder (ADHD).
Note that many of the above changes are still under active consideration and are not definite. For more information regarding proposed revisions to the DSM-5, please visit their website at dsm5.org.
Electroconvulsive therapy, a psychiatric treatment in which seizures are electrically induced in anesthetised patients for therapeutic effect.
Antidepressant-induced mania occurs in 20-40% of people with bipolar disorder. Mood stabilisers, especially lithium, may protect against this effect, but some research contradicts this.
A frequent problem in these individuals is nonadherence to pharmacological treatment; long-acting injectable antipsychotics may contribute to solving this issue in some patients.
A review of validated treatment guidelines for bipolar disorder by international bodies was published in 2020.
Education
Psychosocial interventions can be used for managing acute depressive episodes and for maintenance treatment to aid in relapse prevention. This includes psycho education, cognitive behavioural therapy (CBT), family-focused therapy (FFT), interpersonal and social-rhythm therapy (IPSRT), and peer support.
Information on the condition, importance of regular sleep patterns, routines and eating habits and the importance of compliance with medication as prescribed. Behaviour modification through counselling can have positive influence to help reduce the effects of risky behaviour during the manic phase. Additionally, the lifetime prevalence for bipolar I disorder is estimated to be 1%.
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