Abstract
The present thesis consists of a series of studies that explored the dimensions of the phenomena of depression; clinical, psychological, biological and therapeutic. Study I examined differences in clinical and psychological characteristics of patients with bipolar, endogenous unipolar and nonendogenous depressions. The frequency distribution of Newcastle diagnostic (endogenicity) scores of a large number of patients was plotted in relation to their ICD-9 diagnosis. The relationship of these scores to severity of depression, both subjectively and objectively rated, and to trait anxiety was studied. The results were that these clinical types showed differences in clinical (age of onset, previous number of episodes and family history of affective illness) and psychological characteristics; with bipolar and endogenous unipolar patients showing less personality disturbance than those with nonendogenous depression. The frequency distribution of Newcastle diagnostic scores was unequivocally unimodal, suggesting that mixed forms of depression predominate. Greater endogenicity on the Newcastle Scale was associated with greater severity of depression on objectively but not on subjectively rated scales and with lower trait anxiety. Study II explored the functional activity of 5-HT receptors on platelets using platelet aggregation- techniques in drug-free ill depressive patients, in control subjects, and in patients on prophylactic lithium. It was found that endogenous depressive patients, and patients on prophylactic lithium showed 5-HT receptor supersensitivity in comparison with control subjects. Study III investigated the role of folate in depression by determining plasma and red blood cell concentrations in drug-free ill depressive patients, patients on prophy- lactic lithium, alcoholic patients and control subjects. The therapeutic value of physiological doses of folic acid was studied in patients on prophylactic lithium who had lower plasma folate concentrations in the context of a double-blind placebo-controlled trial over six months. It was shown that plasma and red blood cell folate concentrations were reduced in drug-free depressive patients in comparison with control subjects. Plasma folate concentrations were reduced in patients on prophylactic lithium, particularly unipolars, compared with control subjects. Lower plasma folate concentrations were associated with greater concurrent affective morbidity in alcoholic and lithium-treated patients. On the trial, folate supplements restored lower plasma folate concentrations but were not associated with improvement in residual morbidity. Study IV examined clinical, psychological and biological correlates of antidepressive therapies. Endogenicity scores on the Newcastle Scale showed a curvilinear relationship to response to ECT and antidepressants and a linear relationship to response to prophylactic lithium. Bipolar patients with a family history of depression had more favourable responses to lithium than those with a family history of mania and those without a family history of affective disorder. Unipolar patients with pure familial depressive disease had more favourable responses to lithium than those with sporadic and depressive spectrum diseases. Good responders to prophylactic lithium showed generally less personality disturbance on a variety of measures than fair to poor responders. Patients on prophylactic lithium investigated with DST on two occasions showed non-suppression in one-third of cases, with few changing status from normal to abnormal and vice versa. DST status was not associated with concurrent affective morbidity or with morbidity over the preceding two years. Greater subjective side-effects were associated with greater affective morbid- ity in drug-free ill depressives and in patients on prophylactic lithium. In the latter group greater subjective side-effects were associated with greater affective morbidity over time and with greater personality disturbance. The comparative efficacy of 25-50% reduction in lithium dosage as determined by 12h plasma lithium levels was examined in the context of a double-blind study over one year. Lower plasma lithium levels were associated with a reduction in morbidity, particularly in nonendogenous unipolar patients and with reduction in tremor and subjective side-effects in general. Last, but not least, response to lithium over six months in unipolar illness and over the first year in bipolar illness was strongly associated with long-term response.