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The authors studied 53 patients hospitalized for depression to evaluate possible associations between pretreatment responses to the Minnesota Multiphasic Personality Inventory and behaviorally rated responses to lithium. Patients were randomly assigned to two groups (A and B) in which responders and nonresponders were balanced for sex. For the 18 women in group A, a lithium response scale discriminated responders with 89% accuracy. For the 9 males, a separate scale discriminated responders with 100% accuracy. In a cross-validation, the two scales discriminated responders and nonresponders with 100% accuracy in group B. The empirical methodology of this study suggests an alternative to the theoretical-rational approach of predicting response to antidepressant drugs based on pretreatment depressive symptoms.

In an earlier, separate study, the authors found that human aggression and suicide (a specific aggression-related behavior) were associated with lower levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. That study focused on subjects with personality disorders without affective illness. In the present study they examine the life history of aggression and history of suicidal behavior in 12 subjects with borderline personality disorders without major affective disorder. Histories of aggressive behaviors and of suicide attempts were significantly associated with each other, and each was significantly associated with lower 5-HIAA levels. Altered serotonin metabolism may be a highly significant contributing factor to these behaviors in whatever diagnostic group they occur.

The authors describe the misdiagnosis of an elderly patient with depressive dementia and suggest that lithium may be an effective treatment for some individuals with this disorder, particularly those with apparent bipolar illness.

Normal subjects were admitted to a psychiatric unit devoted to the study and treatment of affective illness. Initially the authors were concerned about the difficulties volunteers might have living with psychiatric patients. However, the volunteers adjusted with relative ease, while the patients' depressive symptoms were exacerbated. Their confrontation with the volunteers "normality" triggered an acute awareness of their underlying sense of failure. This response is analogous to depressed patients' reactions before discharge, when they struggle not only with their special vulnerability to separation and loss but with inevitable challenges to their fragile self-esteem during reintegration into the outside world. The presence of normal volunteers highlighted these issues and led to increased therapeutic work and considerable resolution.

The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.

In order to test the efficacy of the pineal neurohumor melatonin on depression, the hormone was administered in varying doses to six moderately to severely depressed patients and two patients with Huntington's chorea in double-blind crossover study. Melatonin exacerbated symptoms of dysphoria in these patients, as well as causing a loss of sleep and weight and a drop in oral temperature. Melatonin increased cerebrospinal fluid 5-hydroxyindoleacetic acid and calcium in three of four patients studied. The authors discuss the implications of this finding.

The authors review the use of ECT with nine seriously depressed patients at the National Institute of Mental Health over the past 8 years. Despite the patients' poor prior response to a variety of pharmacological treatments, only one patient failed to show a complete response to ECT. With most patients, improvement was quite rapid and dramatic, and all of the ECT responders were free of depression for at least 1 year after treatment. These results are consistent with previous studies; they deserve reemphasis now in light of recent controversies over ECT, including legislative and judicial attempts to restrict its use.

Six women and 6 men who were treated in double-blind fashion major depressive illness did not respond to imipramine or amitriptyline, 150-300 mg/day, during periods of 26-112 days. After the addition of 25 micrograms/day (10 patients) or 50 micrograms/day (2 patients) of L-triiodothyronine (T3), 9 patients showed statistically significant improvement in depression scores; in 8 patients the response was marked. Improvement generally began within 1-3 days and was noted in all aspects of the depressive syndrome; side effects were minimal. T3 did not change plasma levels of imipramine or desipramine or their ratio but did suppress serum thyroxine.

The authors studied pituitary thyrotropin, i.e., thyroid-stimulating hormone (TSH), response to thyrotropin-releasing hormone (TRH) in patients with primary affective disorder. There were no overall differences between either depressed or manic patients and normal controls; however, the TSH response was significantly lower in the unipolar depressed patients than in either bipolar depressed patients or normal subjects. Bipolar patients in the manic phase tended to have a lower response than bipolar depressed patients. In the unipolar group, the TSH response showed a significant negative correlation with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the CSF. These neuroendocrine responses may constitute markers of specific monoamine dysfunction in subgroups of patients with affective illness.

The authors measured cerebrospinal fluid norepinephrine concentrations in manic, depressive, and neurological control patients with and without probenecid administration. Baseline and probenecid norepinephrine values were significantly higher in manic than in depressed patients, who did not differ significantly from the neurological patients. Depressed patients with high levels of anxiety had higher levels of norepinephrine than those with low anxiety. These data suggest that alterations in mood or motor activity may be associated with changes in central norepinephrine metabolism in man.

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar CSF were measured in a group of suicidal schizophrenic patients and in a matched group of nonsuicidal schizophrenic patients. The suicidal group had a significantly lower level. This finding is consistent with reports of low levels of CSF 5-HIAA in suicidal patients with other psychiatric diagnoses and suggests that low CSF 5-HIAA may be a generalized marker of aggressive behavior against the self and others.

The authors studied the effect of a catecholamine-controlled diet on the urinary level of 3-methoxy-4-hydroxyphenylglycol (MHPG) of 6 depressed patients and 6 normal volunteers. The normal subjects showed no change in MHPG levels on or off the diet; the depressed patients showed a significant increase in MHPG while off the diet.

The authors conducted a double-blind placebo-controlled study in which patients with a wide range of manic symptoms were administered 20 mg of naloxone subcutaneously. Naloxone failed to improve manic severity, activation-arousal, or elation-grandiosity for intervals up to 3 hours. Global nurse ratings of mania did not improve over an 8-hour period. The authors suggest that the question of endorphin involvement in mania has not been resolved and recommend clinical studies with longer acting oral narcotic antagonists such as naltrexone.

In this double-blind study, beta-endorphin, 4-15 mg, was administered intravenously to 6 schizophrenic and 4 depressed patients. There were neither significant differences in behavioral ratings between beta-endorphin and placebo for the overall group nor for either the schizophrenic or depressed subgroup. Clinical worsening and improvement were observed in individual schizophrenic patients. There was no evidence of late-appearing therapeutic effects in 4 schizophrenic patients rated for 5 consecutive days after placebo and drug infusions. In 1 patient 10 mg of beta-endorphin produced neuroendocrine effects comparable to those produced by 5 mg of intravenously administered methadone; in 2 other patients it produced large increases in circulating opioid activity as determined by radioreceptor assay. These biological data support the notion that parenterally administered beta-endorphin exerts significant opiate-like activity in vivo.

Unrecognized, untreated, and undertreated depressive disorders extract an inordinate human and economic cost, despite the availability of an extensive array of effective clinical interventions. To enhance the availability and quality of care, the National Institute of Mental Health launched the Depression Awareness, Recognition, and Treatment Program, a multiphase information and education program designed to alert health professionals and the general public to the fact that depressive disorders are common, serious, and treatable. The authors review the development of this program, describing the professional education efforts it supports in anticipation of increased demand for services, the public education campaign launched in May 1988, and highlights of the scientific advances that make the program feasible and timely.

Several investigators have recently challenged the belief that antidepressants can precipitate mania or rapid cycling between mania and depression. With one exception, there appear to be no placebo-controlled studies of switches into mania in bipolar patients during antidepressant treatment. Patients most likely to switch into mania during antidepressant therapy have probably been excluded from maintenance treatment studies and are probably overrepresented in studies at special research facilities. On balance, the available evidence suggests that some bipolar patients become manic, and a few experience rapid cycling, when they are treated with antidepressants. The prevention of these responses will require further research on risk factors and on the antimanic efficacy of coadministered lithium or other mood stabilizers.