Jack L. Croughan

The timing, specificity and clinical prediction of tricyclic drug effects in depression

This research was aimed at studying the rate of action of tricyclic drugs in depressive disorders, specifying the behavioural effects associated with recovery, and predicting clinical response. The research design involved comparison of a recovered group with a group treated for the equivalent four weeks, who showed minimal to no response. The findings indicated significant differences in baseline characteristics between responders and non-responders. Further, the drugs were found to act early in the responders, within the first week of treatment. Specific changes at one week which distinguished responder and non-responder groups occurred in the disturbed affects, and in cognitive functioning. Improvements also occurred in somatic symptoms, but these latter changes were general and not associated with later recovery. At 2 1/2 weeks, all facets of the depressed condition showed positive change in the responders. Implications of the results for assessing rate of tricyclic drug actions, their effects on the interaction of affect and neurochemistry, and the practical application of the results for the clinical situation, are discussed.

Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression

To investigate the clinical specificity of mixed affective states, we compared clinical characteristics of mixed (dysphoric) manics to those of agitated depressed patients. The subjects were inpatients studied in the NIMH Clinical Research Branch Collaborative Study on the Psychobiology of Depression, Biological Studies. Behavior and symptom ratings for depressive and manic symptoms were obtained during a 15-day placebo washout period. Patients with agitated depression were compared to those in acute manic episodes with and without prominent depressive symptoms. Mania ratings clearly distinguished agitated depressed from mixed manic patients. Concerning depression and general psychopathology, mixed manics had more severe agitation, hostility and cognitive impairment than did agitated depressed patients. Depressed mood and anxiety did not differ significantly between the two groups. Nurse ratings for depression and anxiety, based on ward behavior, were similar for mixed manics and agitated depressed patients, while physician-interview rated depression and anxiety were higher in agitated depressed patients. These data support the existence of superimposed depressive and manic syndromes in mixed manics.

Behavioural measurement and drug response characteristics of unipolar and bipolar depression

This research is part of the NIMH--CRB Collaborative Study on the psychobiology of depression. The main objective of the research programme is to test hypotheses concerning the interaction of neurobiological mechanisms and behaviour in the depressive disorders. Part I of the report describes the rationale and the overall approach to measuring behavioural state and outcome in the research programme. Part II reports on the results of applying the behavioural methods to a comparison of the clinical phenomenology of unipolar and bipolar depression. The behavioural patterns expressed during the episode by the two groups are different. Further, the two types are shown to react differently to treatment with tricyclic drugs, reinforcing the thesis that they are qualitatively distinct forms of the depressive disorders.

The Group of Schizoaffective and Related Psychoses: A Follow-up Study

Abstract A follow-up of 114 patients diagnosed as having schizoaffective and related psychoses demonstrated the following: 71% of the patients had a chronic course of illness, 10% an episodic course and 19% were asymptomatic on medication with phenothiazines; 81% of the patients with a chronic course manifested deterioration; none of the patients with an episodic course manifested deterioration, 39% of the patients who were asymptomatic on medication manifested deterioration; the presence or absence of affective symptoms had no predictive value on course of illness or extent of deterioration; our results indicated, therefore, judging by the chronic course and marked deterioration, that the group of schizoaffective and related psychoses appears to resemble schizophrenia rather than affective disorder.

Stress, depression, and mania: relationship between perceived role of stressful events and clinical and biochemical characteristics

We investigated the perceived role of stressful events in episodes of major affective disorder in patients studied in the NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression (Biological Studies). Using items from the Schedule for Affective Disorders and Schizophrenia (SADS), episodes were divided into environment‐sensitive (high perceived role of stressful events) and autonomous (minimal or no perceived role of stressful events). Patients with environment‐sensitive episodes had fewer previous episodes and a longer index episode. The groups did not differ with respect to age, gender, education, socioeconomic group, diagnosis, severity of illness, or eventual response to treatment. Unipolar depressed patients with environment‐sensitive episodes had lower CSF 5‐HIAA than those with autonomous episodes. Among bipolar depressed patients, those with autonomous episodes had elevated excretion of O‐methylated catecholamine metabolites and of epinephrine, while those with environment‐sensitive episodes had normal excretion of cate‐cholamines and metabolites. Manic subjects with environment‐sensitive episodes had elevated norepinephrine excretion, while this was normal in manics with autonomous episodes. Relationships between environmental sensitivity of affective episodes and neurotransmitter function therefore appear to be related to the type of episode.;

Is the major histocompatibility complex linked to genes that increase susceptibility to affective disorder? A critical appraisal

The evidence implicating genes linked to the major histocompatibility complex in the pathogenesis of affective disorder is reviewed, and 10 new multiplex families containing 26 affected siblings are presented. It is shown that when the data are properly analyzed by not dismantling multiplex sibships into all possible sib pairs, no individual data set presents compelling evidence of linkage. The present study is also negative. However, pooling all published families results in moderate evidence for nonrandom assortment.

Psychiatric diagnostic predispositions to alcoholism

Abstract Various authors have described pre-alcoholic psychopathology in female problem drinkers; 1 however, actual studies of rigorously defined antecedent and concurrent psychiatric disorders have been few. More recently, several authors have reported that both affective disorder and antisocial personality are quite prevalent as primary diagnoses in hospitalized alcoholic women, 2,3,4 but the risk of subsequent alcoholism in women with these and other psychiatric syndromes needs to be clarified. In this study we investigate the prevalence of alcoholism in three populations of women with serious psychopathology. The first is a sample of psychiatrically hospitalized women with a history of depression at some time in their lives (hospitalized sample); second is a felon sample of women on probation and parole (felon sample); and third is a sample of female narcotics addicts admitted to the United States Public Health Service facility at Lexington, Kentucky for detoxification and treatment (Lexington sample). Our data set is unique in that despite being collected at different times and at different locations, uniform diagnostic criteria and uniform interview schedules were employed. 5,6

Alcoholism and Alcohol Dependence in Narcotic Addicts: A Prospective Study with a Five-Year Follow-up

In this paper we report on the prediction of mortality, alcohol dependence, and the rate of previously undiagnosed alcoholism in male and female narcotic addicts. These subjects (N = 200) were initially interviewed upon admission to the Clinical Research Center, National Institute of Mental Health, Lexington, Kentucky, and prospectively followed-up and reinterviewed 5 years later (N = 187). The results indicate that alcoholism and alcohol dependence are very prevalent in this sample of addicts. A history of diagnosable alcoholism obtained at admission was a significant predictor of mortality during the follow-up period whereas a history of heavy drinking was associated with increased mortality but not significantly. About one-half of the males and one-quarter of the females met criteria for alcohol dependence during the follow-up period. Both a prior diagnosis of alcoholism and a history of heavy drinking were significant predictors of episodes of alcohol dependence during the follow-up period. In addition, the proportion of subjects positive for alcoholism increased between two- and threefold during the 5-year period. Finally, a history of heavy drinking at any time within the 4 years immediately prior to admission significantly predicted subsequent episodes during the follow-up period.

Sociodemographic and prior clinical course characteristics associated with treatment response in depressed patients.

A sociodemographic and clinical picture is presented of 82 depressed subjects who had an unequivocal response or lack of response to treatment with amitriptyline or imipramine. Patients with less severe depressive illness were found more likely to respond to treatment, while those with psychotic features were more likely to be treatment resistant. Sociodemographic and other prior and current clinical course variables were not predictive of treatment response in depressed patients.

Cortisol measures in primary major depressive disorder with hypersomnia or appetite increase

Morning plasma cortisol response to the 1 mg dexamethasone suppression test along with cortisol levels in blood, cerebrospinal fluid (CSF), and urine were measured in hospitalized male and female patients with primary major depressive disorder who reported hypersomnia (n = 23), or increase in appetite (n = 22). Comparisons were drawn to cortisol levels in patients with primary major depressive disorder who did not report hypersomnia or appetite increase (n = 23) and to normal controls (n = 23), all age- and sex-matched. Depressives with hypersomnia or increased appetite showed higher than normal 24-h urinary free cortisol concentrations. Depressed patients without hypersomnia or appetite increase had in addition to elevated free urinary cortisol concentrations higher than normal morning plasma cortisol levels before and after dexamethasone administration and a higher incidence of cortisol non-suppression after dexamethasone compared to normal subjects. The findings provide preliminary evidence that HPA activation in depression is diminished in the presence of hypersomnia and/or an increased appetite. Studies of the hypothalamic-pituitary-adrenal axis may be useful for differentiating subtypes of depression characterized by hypersomnia or enhanced appetite.