Week 3 MOOD DISORDERS

• Mood disorders


  Two broad classes: unipolar depressive disorders (involve only depressive symptoms) and bipolar depressive disorders (involve depressive and manic symptoms)
• Major depressive disorder


  • Cardinal symptoms include profound sadness and/or guilt, anhedonia, attentional deficits, insomnia, loss of interest, negative attributions, hopelessness, suicidal ideation, social withdrawal, lack of personal hygiene, fatigue, low energy and pain, loss of sexual desire, weight loss/gain, psychomotor deficits
• The intensity and duration of the symptoms in major depressive disorder dissociate them from periods of low mood experienced by everyone
• DSM-5 criteria for major depressive disorder


  Sad mood or loss of pleasure in usual activities, at least five symptoms (counting sad mood and loss of pleasure), sleeping too much or too little, psychomotor retardation or agitation, weight loss or change in appetite, loss of energy, feelings of worthlessness or excessive guilt, difficulty concentrating, thinking or making decisions, recurrent thoughts of death or suicide, symptoms present nearly every day, most of the day, for at least 2 weeks, symptoms are distinct and more severe than a normative response to significant loss
• Major depressive disorder is an episodic disorder, because symptoms tend to be present for a period of time and then clear
• Major depressive episodes often recur—once a given episode clears, a person is likely to experience another episode
• In one study, about 15% of people reported depressive symptoms that persisted for 10 years, and about 40–50% of people who recovered from a first episode of major depression experienced at least one more episode across the 10 years of follow-up
• Persistent depressive disorder (dysthymia)


  Depressive mood for most of the day more than half the time for 2 years (1 year for children and adolescents), at least two of the following: poor appetite or overeating, sleeping too much or too little, low energy, poor self-esteem, trouble concentrating or making decisions, feelings of hopelessness, the symptoms do not clear for more than 2 months at a time, bipolar disorders are not present
• Lifetime prevalence of major depressive disorder is ~10-20% of the general population, and for persistent depressive disorder is ~5%
• Mood disorders are twice as common in women as in men, and the median onset is late teens to early 20's
• Mood disorders have high co-morbidity with other disorders such as substance abuse and anxiety (60% co-morbidity)
• Mood disorders are the third leading cause of disability worldwide and are associated with increased risk of other serious health issues including cardiovascular disease
• Around 2% of those people ever treated for depression in an outpatient setting will die by suicide, and around 4% of those people ever treated for depression in an inpatient setting will die by suicide
• Around 60% of people who commit suicide have had a mood disorder (e.g., major depression, bipolar disorder, dysthymia)
• Bipolar disorders


  • Cardinal symptoms of mania include intense elation or irritability, psychomotor agitation, acting and thinking in highly unusual ways, extroverted behaviour, stream of consciousness monologues, excessive self-confidence, elevated energy levels and reduction in sleep, surge in goal pursuit, easily angered, increased recklessness and risky behaviours
• Bipolar 1


  At least one episode of mania in lifetime, usually occurs with episodes of major depressive disorder
• Bipolar 2


  At least one major depressive episode and at least one episode of hypomania (less severe than mania), but no lifetime episode of mania
• Cyclothymia


  Frequent but mild symptoms of depression, alternating with mild symptoms of mania, although the symptoms do not reach the severity of full-blown hypomanic or depressive episodes
• DSM-5 criteria for manic and hypomanic episodes

  Distinctly elevated or irritable mood, abnormally increased activity or energy, at least three of the following are noticeably changed from baseline (four if mood is irritable): increased in goal directed activity or psychomotor agitation, unusual talkativeness, flight of ideas or subjective impression that thoughts are racing, decreased need for sleep, increased self-esteem, distractibility, excessive involvement in pleasurable activities, symptoms are present most of the day, nearly every day
• Criteria for manic episode

  Symptoms last 1 week, require hospitalisation or included psychosis, symptoms cause significant distress or functional impairment
• Criteria for hypomanic episode

  Symptoms last at least 4 days, clear changes in functioning are observable to others, but impairment is not marked, no psychotic symptoms are present
• DSM-5 Criteria for cyclothymic disorder

  For at least 2 years (or 1 in children and adolescents), numerous periods with hypomanic symptoms that do not meet criteria for a hypomanic episode, numerous periods with depressive symptoms that do not meet criteria for a major depressive episode, the symptoms do not clear for more than 2 months at a time, criteria for a major depressive, manic or hypomanic episode have never been met, symptoms cause significant distress or functional impairment
• Bipolar 1 disorder affects ~0.6% of the general population, while Bipolar 2 and Cyclothymia affect an estimated 1-4% of the general population
• More than half of those with bipolar spectrum disorders report onset before age 25, and bipolar disorder is equally frequent in women and men, though women tend to experience more depressive episodes
• About two-thirds of people diagnosed with bipolar disorder meet diagnostic criteria for a comorbid anxiety disorder, and many report a history of substance abuse
• Bipolar disorder is associated with high rates of unemployment (80-90%), and in a World Mental Health Survey, one in four persons diagnosed with bipolar I disorder reported a suicide attempt and more than half reported suicidal ideation within the past year
• Bipolar disorder has the highest rate of suicide among psychiatric conditions, and is associated with a 10 year reduction in lifespan
• Major depressive disorder shows only moderate heritability (~.37 for identical twins), and genome-wide association studies have failed to identify reliable and specific genetic loci associated with it, though there is some evidence that the serotonin transporter gene may interact with environmental risk factors to predict MDD
• Bipolar disorder is among the most heritable of disorders (~.93), and 56 single nucleotide polymorphisms related to bipolar disorder have been identified, many of which overlap with those suggested to predict schizophrenia
• Role of neurotransmitters in mood disorders

  Too much or too little of serotonin, norepinephrine, and dopamine, with serotonin linked to mood and dopamine to reward, but evidence from neuroimaging is not consistent, perhaps there is an abnormality in the sensitivity of postsynaptic receptors
• Functioning brain abnormalities in mood disorders

  • Abnormal activity in (and connectivity between) emotion and reward centres, including oversensitivity to emotional stimuli and difficulty regulating emotions (amygdala, anterior cingulate, prefrontal cortex), and impaired response to rewarding stimuli and lack of motivation (nucleus accumbens, striatum)
• Cortisol dysregulation


  Hypothalamic-pituitary-adrenocortical (HPA) axis overly active during episodes of major depressive disorder, related to stress reactivity, HPA axis triggers release of cortisol, the main stress hormone, over-secretion of cortisol associated with depressive symptoms, cortisol awakening response predicts likelihood of developing and recurrence of major depressive disorder, prolonged high-levels of cortisol can damage brain structures and increase release of pro-inflammatory cytokines
• Environmental and social factors

  • Childhood adversity (early parental death, physical and/or sexual abuse) increases risk of depression later in life, negative life events (job loss, relationship breakdown, bereavement) often precede depressive episodes, lack of social support (sparse social networks, hostile home environments) increases onset and relapse of mood disorders
• Personality and cognitive factors

  Neuroticism (frequent and intense experience of negative affect), pessimistic and self-critical thoughts (negative triad: negative views of self, the world and the future), negative information-processing bias, belief that desirable outcomes will not occur and that one has no power to change this (hopelessness theory), tendency to dwell on sad experiences and thoughts (rumination theory)
• Treatments of major depressive disorder

  • Biological: four major types of antidepressants (MAOIs, tricyclics, SSRIs, SNRIs), around 60% of patients respond well to medication, unilateral electroconvulsive therapy (ECT) more effective than antidepressants but with side effects, repetitive transcranial magnetic stimulation (rTMS) less effective than ECT but better tolerated, psychosurgery (cingulotomy) only used when all other treatments have failed; Psychological: interpersonal psychotherapy, cognitive therapy, behavioural activation, mindfulness-based approaches, psychodynamic approaches, therapeutic alliance crucial
• Treatments of bipolar disorder

  • Biological: at least 80% of people with bipolar 1 respond to lithium, which decreases relapse rates and severity but has serious side effects; Psychological: psychoeducation, cognitive therapy, family-focused therapy, almost always in combination with medication