Steven K. Secunda

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.

Lithium treatment of mania: Clinical characteristics, specify of symptom change, and outcome

The effects of lithium treatment and prediction of response in 18 manic patients were studied as part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression. Patients were rated using the Mania Diagnostic and Severity Scale (MADS) and an additional battery of behavioral constructs developed for measurement of state and drug response in depressed patients. About 67% of the patients had good treatment outcome after 26 days of lithium treatment. Responders did not differ from nonresponders before treatment with respect to delusions, hallucinations, or irritable-paranoid symptoms. Nonresponders were rated as more anxious than responders before treatment and had higher scores on the Hamilton Rating Scale for Depression. Improvement on the MADS, however, did not correlate with pretreatment behavioral ratings. Patients with relatively high ratings for aspects of behavior not specific to mania tended to improve in these regardless of change in MADS score. Manic patients who were also depressed (44%) had higher mania ratings than manic patients who were not depressed. Patients with concomitant depression and mania had significantly worse overall treatment outcome, although their depression ratings improved during lithium treatment.

Biochemistry and suicidal behavior in depressed patients

The present study was undertaken in order to further explore the relationship between monoamine levels and hypothalamic-pituitary-adrenocortical (HYPAC) functioning and suicidal behavior in depressed patients. One hundred and thirty-two depressed inpatients participated in the NIMH Collaborative Study on the Psychobiology of Depression. Similar to previous reports, our suicide attempters were younger, more likely to be bipolar, had an earlier age at onset, and displayed more psychotic features. No correlation between cortisol hypersecretion or Dexamethasone Suppression Test (DST) nonsuppression and suicide attempts were found. Only the pre-DST evening plasma cortisol distinguished the groups, being lower in the attempter group. We were unable to confirm the previously reported correlation between cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and suicide attempts. Of the monoamines examined, only urinary and plasma 3-methoxy-4-hydroxphenylglycol (MHPG) differed between suicide attempters and nonattempters, showing lower levels in the attempter group. There was a trend for CSF MHPG in the same direction. This latter reduction was restricted to the bipolar group.

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.

Depressive mania versus agitated depression: Biogenic amine and hypothalamic-pituitary-adrenocortical function

The existence of mixed affective states challenges the idea of specific biological abnormalities in depression and mania. We compared biogenic amines and hypothalamic-pituitary-adrenocortical (HPA) function in mixed manic (n = 8), pure manic (n = 11), agitated bipolar depressed (n = 20), and nonagitated bipolar depressed (n = 27) inpatients (Research Diagnostic Criteria). Mixed manics met Research Diagnostic Criteria for primary manic episodes and also met criteria for major depressive episodes except for duration. The norepinephrine metabolite methoxyhydroxy phenthylene glycol (MHPG) was higher in cerebrospinal fluid from mixed manic than from agitated depressed patients, consistent with differences previously reported between the overall samples of depressed and manic patients. Similarly, patients in a mixed state had higher urinary excretion of norepinephrine (NE) and elevated output of NE relative to its metabolites. HPA activity was similar in mixed manic and agitated depressed patients. These data suggest that mixed manics combine certain biological abnormalities considered to be characteristic of mania and of depression.

A method for the determination of sodium, potassium, magnesium and lithium concentrations in erythrocytes.

Abstract A technique for the rapid and accurate estimation of intra-erythrocyte concentrations of Na, K, Li and Mg is described. CoEDTA is used as a marker to estimate plasma trapped in the red cell column ; the use of this compound constitutes a novel departure from other marker substances previously used. Plasma trapping was found to average close to 3% (v/v) of the packed cell column. RBC electrolyte values obtained from healthy control subjects were shown to be in good agreement with values reported in the literature.

Plasma and erythrocyte electrolytes in affective disorders.

Plasma and erythrocyte sodium (Na+), total and free (ultrafiltrable) plasma magnesium (Mg2+) as well as erythrocyte magnesium were measured in patients with affective disorders and in healthy control subjects. Depressed and manic patients had higher total plasma Mg2+ than did hospitalized healthy control subjects, but concentrations of ultrafiltrable Mg2+ did not differ. Although erythrocyte Mg2+ was significantly elevated in the depressed subjects in comparison with that found in the non-hospitalized healthy controls, this difference was not seen between the depressives and the hospitalized healthy controls. Depressed, manic or healthy control subjects did not differ with respect to either plasma or erythrocyte.

Expressive characteristics of anxiety in depressed men and women

This study was aimed at identifying the expressive, movement, and social behaviors associated with anxiety in the syndrome of major depression. The sample consisted of 97 hospitalized male and female depressed patients. Expressive and social behaviors were evaluated prior to treatment in a structured videotaped interview. Anxiety was measured using a multi-vantaged approach including doctors rating, nurses rating, patient self-report, and a separate video rating. Results indicate that anxiety was significantly associated with agitation, distressed facial expression, bodily discomfort, and poor social interaction in both sexes. Men and women differed in certain respects: anxiety was highly related to motor retardation in women only, and to hostility in men only. Differences in the pattern of expressive behavior between high and low anxious, depressed patients were clearly significant, and several were large enough to serve as clinical indicators. These findings help to characterize the expressive features of anxiety in the context of severe depression, and add to the growing literature on sex differences in depression.

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.

Mania: Sympathoadrenal function and clinical state

We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine relative to its metabolites, but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania.