Mood is a pervasive and sustained feeling tone that is experienced internally and influences a person’s behaviour and perception of the world. Affect is the external expression of mood. Mood can be normal, elevated, or depressed. Healthy persons experience a wide range of moods and have an equally large repertoire of affective expressions; they feel in control of their moods and affect. Mood disorders are a group of clinical conditions characterised by a loss of that sense of control and a subjective experience of great distress.
Patients with depressed mood experience a loss of interest; poor energy; guilt feelings; poor concentration; loss of appetite; poor self-esteem; feelings of hopelessness and helplessness; thoughts of death; passive death wishes; or suicidal thoughts. Other signs and symptoms of mood disorders include change in activity level and cognitive abilities. Depressive disorders result in impaired interpersonal, social and occupational functioning.
According to <em>DSM 5</em>, to diagnose major depressive disorder, the following criteria should be fulfilled:
I: Depressed mood or a loss of interest or pleasure in daily activities for more than two weeks. Mood represents a change from the person’s baseline.
II: Impaired function: Social, occupational and educational. Specific symptoms, at least five of the nine criteria listed below, present nearly every day:
1: Depressed mood or irritability most of the day, nearly every day, as indicated by either subjective report (eg, feels sad or empty) or observation made by others (eg, appears tearful). 2: Decreased interest or pleasure in most activities, most of each day. 3: Significant weight change (5 per cent) or change in appetite. 4: Change in sleep: Insomnia or hypersomnia. 5: Change in activity: Psychomotor agitation or retardation. 6: Fatigue or loss of energy. 7: Guilt/worthlessness, feelings of worthlessness or excessive or inappropriate guilt. 8: Concentration: Diminished ability to think or concentrate, or more indecisiveness. 9: Suicidality: Thoughts of death or suicide, or has suicide plan.
The episode is not due to the effects of a substance or to a medical condition. The occurrence is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders. There has never been a manic episode or a hypomanic episode.
Depression is a major cause of morbidity worldwide. Lifetime prevalence varies widely, from 3 per cent in Japan to 17 per cent in the US. In most countries, the number of people who would suffer from depression during their lives falls within an 8-to-12 per cent range. A universal observation is the twofold greater prevalence of major depressive disorder in women than in men. The reasons for the difference are hypothesised to involve hormonal differences, the effects of childbirth, difference in psychosocial stressors for women, and behavioural models of learned helplessness.
The mean age of onset for major depressive disorder is about 40 years, with 50 per cent of all patients having an onset between the ages of 20 and 50. Recent epidemiological data suggest that the incidence of major depressive disorder may be increasing among people younger than 20 years of age. This may be related to the increased use of alcohol and drug abuse in this age group. Major depressive disorder occurs most often in people without close interpersonal relationships or in those who are divorced or separated. No correlation has been found between socioeconomic status and major depressive disorder.
Individuals with major mood disorders are at an increased risk of having one or more comorbid Axis I disorders. The most frequent disorders are substance use problems, panic disorder, obsessive-compulsive disorder (OCD) and social anxiety disorder. On the other hand, individuals with substance use and anxiety disorders have an elevated risk of lifetime or current comorbid mood disorder.
Despite decades of research, scientists around the world still don’t really know the cause of depression. It is generally believed that depression is caused by a complex interaction and combination of biological, psychological and social factors, what is known as the biopsychosocial model of causation, and this is the most generally accepted theory among mental health professionals and researchers.
Of the biogenic amines, norepinephrine and serotonin are the two neurotransmitters most implicated in the pathophysiology of depression.
With the huge effect that the selective serotonin reuptake inhibitors (SSRIs) have made on the treatment of depression, serotonin has become the biogenic amine neurotransmitter most commonly associated with depression. Depletion of serotonin may precipitate depression, and some patients with suicidal impulses have low cerebrospinal fluid (CSF) concentrations of serotonin metabolites and low concentrations of serotonin uptake sites on platelets.
Dopamine has also been theorised to play a role in depression. The data suggest that dopamine activity may be reduced in depression and increased in mania. Theories suggest that the mesolimbic dopamine pathway may be dysfunctional in depression and that the dopamine D1 receptor may be hypoactive in depression.
The role of acetylcholine has been mentioned and abnormal levels of choline, which is an ACh precursor, have been found at autopsy in the brains of some depressed patients, perhaps reflecting abnormalities in cell phospholipid composition.
Activity of the gene coding for the neurokinin brain-derived neurotrophic growth factor (BDNF) is decreased after chronic stress, as is the process of neurogenesis. Protracted stress thus can induce changes in the functional status of neurons and, eventually, cell death.
Recent studies in depressed humans indicate that a history of early trauma is associated with increased hypothalmic-pituitary-adrenal (HPA) activity accompanied by structural changes (ie, atrophy or decreased volume) in the cerebral cortex.
Elevated HPA activity is a hallmark of mammalian stress responses and one of the clearest links between depression and the biology of chronic stress. Elevated HPA activity in depression has been well documented.
Depression is associated with a premature loss of deep (slow-wave) sleep and an increase in nocturnal arousal.
Depressive disorders are also associated with several immunological abnormalities, including decreased lymphocyte proliferation in response to mitogens and other forms of impaired cellular immunity.
The most consistent abnormality observed in CT scan and MRI scan in the depressive disorders is an increased frequency of abnormal hyper-intensities in subcortical regions, such as periventricular regions, the basal ganglia and the thalamus.
PET findings in depression show a decreased anterior brain metabolism, which is generally more pronounced on the left side.
Numerous family, adoption and twin studies have well documented the heritability of depression.
A long-standing clinical observation is that stressful life events more often precede first episodes, rather than subsequent episodes, of depression.
According to cognitive theory, depression results from specific cognitive distortions present in a person susceptible to depression. Aaron Beck postulated a cognitive triad of depression that consists of negative views about the self, future and life.
Learned helplessness is behaviour typical of a human or non-human animal and occurs where an animal endures repeatedly painful or otherwise aversive stimuli that it is unable to escape or avoid. After such experience, the organism often fails to learn or accept ‘escape’ or ‘avoidance’ in new situations where such behaviour would likely be effective.
Good history-taking, Mental State Examination and psychiatric formulation are the cornerstones in depression diagnosis and treatment. Patients with depressive disorders usually go to their GP with somatic complaints. Most medical causes of depression can be detected by a good history, a complete physical and neurological examination and routine blood and urine tests.
Treatment of patients with depression should be holistic, personal and should be directed towards immediate, intermediate and long-term goals. First, the suicide risk should be considered: Does the patient need hospitalisation or outpatient treatment? Second, a complete diagnostic evaluation and psychiatric formulation of the patient is necessary.
The use of antidepressants approximately doubles the chances that a depressed patient will recover in one month. All currently available antidepressants may take up to three-to-four weeks to exert significant therapeutic effects, although they may begin to show their effects earlier. Choice of antidepressants is usually determined by side-effect profile of medications, as well as patient and doctor preferences, and previous response to a specific antidepressant.
The most common clinical mistake leading to an unsuccessful trial of an antidepressant drug is the use of too low a dosage for too short a time. Unless adverse events prevent it, the dosage of an antidepressant should be raised to the maximum recommended level and maintained at that level for at least four or five weeks before a drug trial is considered unsuccessful.
Antidepressant treatment should be maintained for at least six-to-nine months after complete remission. Prophylactic treatment with antidepressants is effective in reducing the number and severity of recurrences. Prophylactic treatment is suggested with the seriousness of previous depressive episodes.
Electroconvulsive therapy (ECT) is a procedure done under general anaesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. The seizure usually lasts less than a minute. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental illnesses.
ECT is recommended when depression is not responding to other treatments, or when there is a need for a rapid response (such as when there is a high risk of suicide or when the depression itself is threatening the health of the person). ECT can be a life-saving treatment.
ECT results in rapid resolution of the symptoms of major depression. Remission, and complete resolution of depression’s symptoms, is reported to range from 70-to-90 per cent with ECT treatment.
Transcranial magnetic stimulation has been used for 15 years in the treatment of depression. It consistently produces small-to-medium effect sizes in people who are usually resistant to at least one type of medication.
In the last few decades, an important role for glutamate in mood modulation has been hypothesised and ketamine, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, has been demonstrated to be effective in both major depressive disorders and treatment-resistant depression disorder.
Overall, the antidepressant effect of ketamine may be observed after a few hours of a single intravenous infusion, but the long-lasting, sustained, antidepressant-like effects of ketamine need to be further investigated. Unless better remission rates have been suggested over time, ketamine should be currently investigated as an augmentation therapy (together with other antidepressant drugs) rather than as a monotherapy.
Cognitive therapy, originally developed by Aaron Beck, focuses on the cognitive distortions. Such distortions include selective attention to the negative aspects of circumstances and unrealistically morbid inferences regarding self, future and life.
Behaviour therapy is based on the hypothesis that maladaptive behavioural patterns result in a person receiving little positive feedback and perhaps rejection from society. By addressing maladaptive behaviours in therapy, patients learn to function in the world in such a way that they receive positive reinforcement.
Interpersonal therapy, developed by Gerald Klerman, focuses on a patient’s current interpersonal problems. This therapy is based on two assumptions: Current interpersonal problems are likely to have their roots in early dysfunctional relationships, and current inter-personal problems are likely to be involved in precipitating or perpetuating the current depressive symptoms.
Mood disorders are characterised by sleep disturbance. Mania tends to be characterised by a decreased need for sleep, whereas depression can be associated with either hypersomnia or insomnia. Sleep deprivation may precipitate mania in patients who are bipolar I and temporarily relieve depression in those who are unipolar. Approximately 60 per cent of depressive disorder patients exhibit significant but transient benefits from total sleep deprivation.