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Causes of Anxiety Disorders (Physical Disorder or Drug)

Anxiety can also be caused by a general medical disorder or the use or discontinuation (withdrawal) of a drug.

General medical disorders that can cause anxiety include the following:

  • Heart disorders, such as:
    • Heart failure; and
    • Abnormal heart rhythms (arrhythmias)
  • Hormonal (endocrine) disorders, such as:
    • An overactive adrenal gland (hyperadrenocorticism); or
    • Thyroid gland (hyperthyroidism); or
    • A hormone-secreting tumour called a pheochromocytoma.
  • Lung (respiratory) disorders, such as:
    • Asthma; and
    • Chronic obstructive pulmonary disease (COPD).

Even fever can cause anxiety.

Anxiety may occur in dying people as a result of fear of death, pain, and difficulty breathing.

Drugs that can trigger anxiety include the following:

  • Alcohol;
  • Stimulants (such as amphetamines);
  • Caffeine;
  • Cocaine;
  • Many prescription drugs, such as corticosteroids; and
  • Some over-the-counter weight-loss products, such as those containing:
    • The herbal product guarana;
    • Caffeine; or
    • Both.

Withdrawal from alcohol or sedatives, such as benzodiazepines (used to treat anxiety disorders), can cause anxiety and other symptoms, such as insomnia and restlessness.

Causes of Anxiety Disorders

The causes of anxiety disorders are not fully known, but the following may be involved:

  • Genetic factors (including a family history of an anxiety disorder);
  • Environment (such as experiencing a traumatic event or stress);
  • Psychologic makeup; and/or
  • A physical condition.

An anxiety disorder can be triggered by environmental stresses, such as the breakup of a significant relationship or exposure to a life-threatening disaster.

When an individual’s response to stresses is inappropriate or an individual is overwhelmed by events, an anxiety disorder can arise. For example, some individuals find speaking before a group exhilarating. But others dread it, becoming anxious with symptoms such as sweating, fear, a rapid heart rate, and tremor. Such individuals may avoid speaking even in a small group.

Anxiety tends to run in families. Doctors think some of this tendency may be inherited, but some is probably learned by living with anxious individuals.

Did You Know?

  • Anxiety disorders are the most common type of mental health disorder.
  • Individuals with an anxiety disorder are more likely than other individuals to have depression.

How Does Anxiety Affect Performance?

The effects of anxiety on performance can be shown on a curve.

As the level of anxiety increases, performance efficiency increases proportionately, but only up to a point.

As anxiety increases further, performance efficiency decreases.

Before the peak of the curve, anxiety is considered adaptive because it helps people prepare for a crisis and improve their functioning.

Beyond the peak of the curve, anxiety is considered maladaptive because it produces distress and impairs functioning.

The Yerkes-Dodson Law

The Yerkes–Dodson law is an empirical relationship between arousal and performance, originally developed by psychologists Robert M. Yerkes and John Dillingham Dodson in 1908.

The law dictates that performance increases with physiological or mental arousal, but only up to a point.

Levels of Arousal (or Anxiety)

Research suggests that different tasks require different levels of arousal for optimal performance. For example:

  • Difficult or intellectually demanding tasks may require a lower level of arousal (to facilitate concentration); whereas
  • Tasks demanding stamina or persistence may be performed better with higher levels of arousal (to increase motivation).

Because of task differences, the shape of the curve can be highly variable (Diamond et al., 2007).

  • For simple or well-learned tasks, the relationship is monotonic, and performance improves as arousal increases.
  • For complex, unfamiliar, or difficult tasks, the relationship between arousal and performance reverses after a point, and performance thereafter declines as arousal increases.

What is the Relationship to Glucocorticoids?

A 2007 review of the effects of stress hormones (glucocorticoids, GC) and human cognition revealed that memory performance versus circulating levels of glucocorticoids does manifest an upside down U shaped curve and the authors noted the resemblance to the Yerkes-Dodson curve.

For example, long-term potentiation (LTP) (the process of forming long-term memories) is optimal when glucocorticoid levels are mildly elevated whereas significant decreases of LTP are observed after adrenalectomy (low GC state) or after exogenous glucocorticoid administration (high GC state).

This review also revealed that in order for a situation to induce a stress response, it has to be interpreted as one or more of the following:

  • Novel;
  • Unpredictable;
  • Not controllable by the individual; and/or
  • A social evaluative threat (negative social evaluation possibly leading to social rejection).

It has also been shown that elevated levels of glucocorticoids enhance memory for emotionally arousing events but lead more often than not to poor memory for material unrelated to the source of stress/emotional arousal (Lupien et al, 2007).

References

Diamond, D.M., Campbell, A.M., Park, C.P., Halonen, J. & Zoladz, P.R. (2007). The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes–Dodson Law. Neural Plasticity. 2007: 60803. http://dx.doi.org/10.1155/2007/60803.

Lupien, S.J., Maheu, F., Tu, M., Fioco, A. & Schramek, T.E. (2007) The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition. Brain and Cognition. 65(3), pp.209-237. https://doi.org/10.1016/j.bandc.2007.02.007.

Yerkes, R.M. & Dodson, J.D. (1908) The Relation of Strength of Stimulus to Rapidity of Habit-Formation. Journal of Comparative Neurology and Psychology. 18, pp.459-482.

Mental Health & Social Support

Everyone requires a social network to satisfy the human need to be cared for, accepted, and emotionally supported, particularly in times of stress.

Research has shown that strong social support may significantly improve recovery from both physical and mental illnesses.

Changes in society have diminished the traditional support once offered by neighbours and families.

As an alternative, self-help groups and mutual aid groups have sprung up throughout the country.

Some self-help groups, such as Alcoholics Anonymous and Narcotics Anonymous, focus on addictive behaviour.

Others act as advocates for certain segments of the population, such as the disabled and older people, or provide support for family members of people who have a severe mental illness.

Causes of Mental Illness

Currently, mental illness is thought to be caused by a complex interaction of factors, including the following:

  • Hereditary;
  • Biologic (physical factors);
  • Psychologic; and/or
  • Environmental (including social and cultural factors).

Research has shown that for many mental health disorders, heredity plays a part. Often, a mental health disorder occurs in people whose genetic make-up makes them vulnerable to such disorders. This vulnerability, combined with life stresses, such as difficulties with family or at work, can lead to the development of a mental disorder.

Also, many experts think that impaired regulation of chemical messengers in the brain (neurotransmitters) may contribute to mental health disorders.

Brain imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), often show changes in the brains of people with a mental health disorder.

Thus, many mental health disorders appear to have a biologic component, much like disorders that are considered neurologic (such as Alzheimer disease).

However, whether the changes seen on imaging tests are the cause or result of the mental health disorder is unclear.

Identifying Mental Illness

Mental illness cannot always be clearly differentiated from normal behaviour.

For example, distinguishing normal bereavement from depression may be difficult in people who have had a significant loss, such as the death of a spouse or child, because both involve sadness and a depressed mood.

In the same manner, deciding whether a diagnosis of anxiety disorder applies to people who are worried and stressed about work can be challenging because most people experience these feelings at some time.

The line between having certain personality traits and having a personality disorder can be blurry.

Thus, mental illness and mental health are best thought of as being on a continuum.

Any dividing line is usually based on the following:

  • How severe the symptoms are;
  • How long symptoms last; and
  • How much symptoms affect the ability to function in daily life.

Can We Identify Genetic Overlap & Novel Risk Loci for Attention-Deficit/Hyperactivity Disorder & Bipolar Disorder?

Research Paper Title

Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder.

Background

Differential diagnosis between childhood onset attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) remains a challenge, mainly due to overlapping symptoms and high rates of comorbidity.

Despite this, genetic correlation reported for these disorders is low and non-significant.

Here the researchers aimed to better characterise the genetic architecture of these disorders utilising recent large genome-wide association studies (GWAS).

Methods

They analysed independent GWAS summary statistics for ADHD (19,099 cases and 34,194 controls) and BD (20,352 cases and 31,358 controls) applying the conditional/conjunctional false discovery rate (condFDR/conjFDR) statistical framework that increases the power to detect novel phenotype-specific and shared loci by leveraging the combined power of two GWAS.

Results

They observed cross-trait polygenic enrichment for ADHD conditioned on associations with BD, and vice versa.

Leveraging this enrichment, they identified 19 novel ADHD risk loci and 40 novel BD risk loci at condFDR <0.05.

Further, they identified five loci jointly associated with ADHD and BD (conjFDR < 0.05). Interestingly, these five loci show concordant directions of effect for ADHD and BD.

Conclusions

These results highlight a shared underlying genetic risk for ADHD and BD which may help to explain the high comorbidity rates and difficulties in differentiating between ADHD and BD in the clinic.

Improving our understanding of the underlying genetic architecture of these disorders may aid in the development of novel stratification tools to help reduce these diagnostic difficulties.

Reference

O’Connell, K.S., Shadrin, A., Bahrami, S., Smeland, O.B., Bettella, F., Frei, O., Krull, F., Askeland, R.B., Walters, G.B., Davíðsdóttir, K., Haraldsdóttir, G.S., Guðmundsson, Ó.Ó., Stefánsson, H., Fan, C.C., Steen, N.E., Reichborn-Kjennerud, T., Dale, A.M., Stefánsson, K., Djurovic, S. & Andreassen, O.A. (2019) Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder. Molecular Psychiatry. doi: 10.1038/s41380-019-0613-z. [Epub ahead of print].

Is Varenicline a Useful Target Compound for Improving Cognitive Impairment in Schizophrenia?

Research Paper Title

Varenicline for cognitive impairment in people with schizophrenia: systematic review and meta-analysis.

Background

People with schizophrenia frequently have cognitive dysfunction, which does not respond to pharmacological interventions. Varenicline has been identified as a potential treatment option for nicotinic receptor dysfunction with a potential to treat cognitive impairment in schizophrenia.

Methods

The researchers conducted a systematic review of Pubmed, Embase, Psycinfo, CINAHL and the Cochrane Schizophrenia Trial Registry for randomised controlled trials of varenicline in people with schizophrenia for cognitive dysfunction.

They excluded trials among people with dementia. They then undertook a meta-analysis with the primary outcome of difference in change of cognitive measures between varenicline and placebo as well as secondary outcomes of difference in rates of adverse events.

They also conducted a sensitivity analysis on smoking status and study duration.

Results

The researchers included four papers in the meta-analysis (n = 339).

Varenicline was not superior to placebo for:

  • Overall cognition (SMD = -0.022, 95% CI -0.154-0.110; Z = -0.333; p = 0.739);
  • Attention (SMD = -0.047, 95% CI -0.199-0.104; Z = -0.613; p = 0.540);
  • Executive function (SMD = -0.060, 95% CI -0.469-0.348; Z =- 0.290; p = 0.772); or
  • Processing speed (SMD = 0.038, 95% CI -0.232-0.308; Z = 0.279; p = 0.780).

There was no difference in psychotic symptoms, but varenicline was associated with higher rates of nausea.

Sensitivity analyses for smoking status and study duration did not alter the results.

Conclusions

Within the present literature, varenicline does not appear to be a useful target compound for improving cognitive impairment in schizophrenia.

Based on these results, a trial would need over 2,500 participants to be powered to show statistically significant findings.

Reference

Tanzer, T., Shah, S., Benson, C., De Monte, V., Gore-Jones, V., Rossell, S.L., Dark, F., Kisely, S., Siskind, D. & Melo, C.D. (2019) Varenicline for cognitive impairment in people with schizophrenia: systematic review and meta-analysis. Psychopharmacology. doi: 10.1007/s00213-019-05396-9. [Epub ahead of print].

Primary Mental Health Integration Requires Considerable Organisational Investments

Research Paper Title

Time and Organizational Cost for Facilitating Implementation of Primary Care Mental Health Integration.

Background

Integrating mental health services into primary care settings is complex and challenging. Although facilitation strategies have successfully supported implementation of primary care mental health integration and other complex innovations, we know little about the time required or its cost.

The objective of this study was to examine the time and organisational cost of facilitating implementation of primary care mental health integration.

Methods

One expert external facilitator and two internal regional facilitators who helped healthcare system stakeholders, e.g., leaders, managers, clinicians, and non-clinical staff, implement primary care mental health integration at eight clinics.

Implementation facilitation tailored to the needs and resources of the setting and its stakeholders.

The researchers documented facilitators’ and stakeholders’ time and types of activities using a structured spreadsheet collected from facilitators on a weekly basis. We obtained travel costs and salary information. We conducted descriptive analysis of time data and estimated organisational cost.

Results

The external facilitator devoted 263 h (0.09 FTE), including travel, across all 8 clinics over 28 months. Internal facilitator time varied across networks (1792 h versus 1169 h), as well as clinics. Stakeholder participation time was similar across networks (1280.6 versus 1363.4 person hours) but the number of stakeholders varied (133 versus 199 stakeholders).

The organisational cost of providing implementation facilitation also varied across networks ($263,490 versus $258,127). Stakeholder participation accounted for 35% of the cost of facilitation activities in one network and 47% of the cost in the other.

Conclusions

Although facilitation can improve implementation of primary care mental health integration, it requires substantial organisational investments that may vary by site and implementation effort.

Furthermore, the cost of using an external expert to transfer facilitation skills and build capacity for implementation efforts appears to be minimal.

Reference

Ritchie, M.J., Kirchner, J.E., Townsend, J.C. Pitcock. J.A., Dollar, K.M. & Liu, C.F. (2019) Time and Organizational Cost for Facilitating Implementation of Primary Care Mental Health Integration. Journal of General Internal Medicine. doi: 10.1007/s11606-019-05537-y. [Epub ahead of print].