Common clinical condition characterized by pathological lowering of MOOD, and inability to experience pleasure (ANHEDONIA). Associated symptoms include SLEEP disturbance with early wakening; poor APPETITE with body weight loss; impaired concentration and memory function; and low or absent sex drive. The disorder tends to be recurrent, and may become chronic. Psychotic symptoms may occur, with auditory HALLUCINATION (taking the form of derogatory voices) and DELUSION (of the nihilistic type). The condition varies widely in severity: mild depressions may go undetected clinically, while rarer, more severe forms of the condition may be lethal, leading to death through SUICIDE or self-neglect. Overall, the condition represents a major public health problem, with one in three of us suffering some degree of depressive disturbance in our lifetime. Depression is encountered in all cultures, and has always been with us—the disorder was described by the Ancient Greeks. There is some evidence that the incidence of the disorder is increasing: the World Health Organization estimates that depression will be the second leading cause of disability and health problems by 2020.
Clinically important depressive disorder is part of a spectrum of affective disorders, which includes DYSTHYMIC DISORDER (a long-standing characteristic predisposition to low mood), UNIPOLAR DEPRESSION (recurrent episodes of pathological low mood) and bipolar depression (MANIC DEPRESSION) where episodes of both low mood and pathological elevation of mood occur recurrently on different occasions. The aetiology of the disorder is complex—there is certainly a marked genetic component (most evident in the form known as manic depression), but social factors and STRESS such as early adverse experience and unpleasant life events are also important. The fact that drugs acting on monoamine systems are effective in depression has led to the idea that SEROTONIN, NORADRENALINE and perhaps DOPAMINE systems may be dysfunctional in depressive disorder. Drugs like PROZAC (fluoxetine) block the REUPTAKE of serotonin by neurons and increase availability of the neurotransmitter.
This may lead to the downregulation of presynaptic 5HT1a autoreceptors (see SEROTONIN RECEPTORS) in the cell bodies of the serotonergic neurons in the brainstem with a resultant increase cell firing and increased activity of the system. Other drugs may have similar actions on the noradrenergic system, and some affect both. Experimental depletion of 5HT or blockade of noradrenaline synthesis provokes temporary relapse in treated depressives. Disordered CORTISOL function may play an important role, but it is not clear whether the high levels of cortisol seen in some patients are a cause or an effect of the condition. Recent studies suggest that the expression of a neuroprotective protein, BRAIN-DERIVED NEURO TROPHIC FACTOR, may mediate the effects of stress and antidepressants in a reciprocal manner. FUNCTIONAL NEUROIMAGING studies show functional and structural abnormalities in some depressed patients, with reduced activity in the FRONTAL CORTEX and a reduction in size of the PREFRONTAL CORTEX. Chronic depression may lead to atrophy of the HIPPOCAMPUS, possibly mediated by CORTICOSTEROID dysfunction, with attendant deficits in LEARNING and MEMORY.
Most depression is treated with chemical ANTIDEPRESSANT drugs, such as the serotonin selective reuptake inhibitors (SSRIs), TRICYCLICS or MONOAMINE OXIDASE INHIBITORS. The drugs are highly effective with response rates of 60–70%. Onset of response takes time and is within 3 to 4 weeks of commencing the medication. Psychological therapies, such as COGNITIVE-BEHAVIOURAL THERAPY are also effective. Severe drug resistant depression may be treated with ELECTROCONVULSIVE THERAPY (ECT), which, despite its negative media pro file, is safe and highly effective. Rarely, very severe, chronic and intractable disorders may be treated by neurosurgical approaches, as in PSYCHOSURGERY.
IAN C.REID
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