Denis F. Darko

Bereavement, depression, and immune function

This study evaluates whether recently widowed women who fulfill criteria for a depressive syndrome differ in their immune responses from widows who do not. Twenty-one middle-aged widows who had lost their spouses 2 months before the initial evaluation and 21 demographically matched married women were evaluated at approximately 6-month intervals for 13 months. Evaluations consisted of diagnostic interviews using the Schedule for Affective Disorders and Schizophrenia, Hamilton Rating Scale for Depression, and Beck Depression Inventory. Immune function was measured by total lymphocyte counts, natural killer (NK) cell activity, mitogen responsiveness to concanavalin A, and T-cell subsets. There were no statistically significant differences on any of the immune measures between the entire cohort of widows and control subjects. However, the subset of widows who met DSM-III-R criteria for major depressive syndromes demonstrated impaired immune function (lower NK cell activity and lower mitogen stimulation) compared with those who did not meet criteria for major depression. This study suggests a relationship between impaired immune function and depression in women experiencing the stress of bereavement.

The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group

In order to determine the effect of an anticholinergic agent on mood and sleep, scopolamine (0.4 mg IM) was administered before bedtime for three consecutive nights to 10 depressed patients (8 with a history of alcohol abuse) and 10 normal comparison subjects. The patients had a small, statistically significant antidepressant response on the second morning of treatment. Scopolamine inhibited rapid eye movement (REM) sleep and prolonged REM latency equally in depressed patients and the normal comparison group. Partial tolerance to the REM inhibiting effect of scopolamine developed between the first and third night of treatment. A REM rebound occurred during recovery nights. These results are consistent with concepts relating central cholinergic mechanisms to the control of REM sleep. Compared with controls, patients showed a greater increase in Stage 2 and Stage 2% and a lesser and increase in Delta (Stage 3 and 4) sleep % and Stage 4% on the first night of treatment. Further, well-controlled studies are needed to determine whether anticholinergic drugs possess clinically significant antidepressant effects.

Neutrophilia and lymphopenia in major mood disorders

Alterations in peripheral blood leukocyte distribution in major depression, including lymphopenia, neutrophilia, eosinopenia, and monocytopenia, have been described. The present study was designed to replicate these results, but with methodological improvements, including age-, sex-, and race-matched control subjects; DSM-III and Research Diagnostic Criteria diagnoses based on the Schedule for Affective Disorders and Schizophrenia interview; objective and subjective severity of depression measured quantitatively; and consideration of psychosocial stressors (DSM-III, Axis IV). We found relative lymphopenia and absolute neutrophilia and leukocytosis in depression, but did not find decreased numbers of eosinophils or monocytes. The relative lymphopenia and absolute neutrophilia were present in the subgroup of only unipolar depressed patients, but not in the bipolar, currently depressed subgroup. However, these blood cell changes were not found in a subgroup of patients who had been medication free greater than or equal to 1 month but only in the subgroup of patients using medication at the time of phlebotomy. Groups formed on the basis of psychosocial stress levels were not found to have significant significant intergroup differences in white blood cell (WBC) counts. The clinical significance of these findings needs study. While leukocytosis and neutrophilia can be found in major depression, these changes are perhaps secondary to medication use.

Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression ☆

To assess cellular immune status and the hypothalamic-pituitary (HP) axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma levels of cortisol, adrenocorticotropin hormone (ACTH), growth hormone (GH), and prolactin (PRL). Twenty patients with major depression were compared with 20 control subjects matched for age, sex, and race. The dose-response curves for concanavalin-A (Con-A) and phytohemagglutinin (PHA) stimulation were not significantly different between the two groups. The patients had decreased Con-A-stimulated T-lymphocyte proliferation when compared to the control subjects, but only at the lowest suboptimal concentration of Con-A. None of the four concentrations of PHA-stimulated proliferation were different between the two groups, neither was PHA-induced interleukin-2 production. Within the patient group only, plasma prolactin (PRL) correlated significantly with stimulated lymphocyte proliferation using two optimal concentrations of PHA and one optimal concentration of Con-A, when the proliferation was expressed using the stimulation index.

Antidepressant treatment and the occurrence of mania in bipolar patients admitted for depression

We examined the records of 33 patients who had 70 inpatient admissions with a diagnosis of bipolar affective disorder, depressed. During 14 of these admissions, a switch occurred from depression into mania. We compared the treatment patients were on at the time of their switch to treatment during the 56 admissions where there was no switch. We conclude that clinicians must be prepared for depressed bipolar patients to switch to mania regardless of treatment status.

Plasma beta-endorphin and natural killer cell activity in major depression: A preliminary study

Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.

Immune cells and the hypothalamic-Pituitary axis in major depression

To explore changes in immune cell status with changes in the hypothalamic-pituitary (HP) axis in 20 patients with major depression as compared with 20 age-, sex-, and race-matched control subjects, we examined peripheral blood mononuclear cells (PBMC) for total T-cells (T3), total B-cells (B1), two T-cell subsets (T4 and T8), and natural killer cells (NKH1), and we measured the plasma level of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL). The ratio of T4/T8 was increased in the patients. Within the group of control subjects only, increasing age correlated significantly with decreasing plasma PRL. Within the group of patients only, GH positively correlated significantly with T8 and NKH1, as did PRL with NKH1. No between-groups difference was found for T3, B1, T4, T8, NKH1, cortisol, ACTH, GH, or PRL.

Peripheral White Blood Cells and Hpa Axis Neurohomrmones in Major Depression

Alterations in peripheral blood leukocyte distribution in major depression, including leukocytosis, neurotrophilia and lymphopenia, have been described. To assess peripheral white blood cells and the hypothalamic-pituitary (HP) axis in drug-free patients with major depression, we measured the total white blood cell count (WBC), and percentage of lymphocytes, and the plasma levels of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin (PRL). Twenty male patients with major depression had relative lymphopenia and leukocytosis when compared with 20 age, sex and racematched control subjects. Elevated Beck and Hamilton depression scores correlated with a decreased percentage of lymphocytes, in a group of all subjects combined. There was a weak tendency for elevated growth hormone to correlate with relative lymphopenia in the control subjects only. Relative lymphopenia and leukocytosis may be a part of the psychobiology of major depression.

Menstrual Dysfunction in Bulimia

AbstractThirty-six consecutive patients with bulimia were evaluated for menstrual functioning. Nearly half the patients were amenorrheic or had markedly irregular menstrual periods. Low body weight in the past was strongly correlated with menstrual dysfunction at present, although present body weight was much less well correlated. Neither overexercise nor other psychiatric diagnoses were associated with menstrual dysfunction, but bulimic patients with menstrual dysfunction reported more childhood sexual abuse, had poorer response to treatment, and tended to have had their disorder for a longer period of time before seeking treatment.

Some Correlates of Treatment Response to a Multicomponent Psychotherapy Program in Outpatients with Eating Disorders

AbstractThe authors evaluated 38 consecutive patients admitted to an intensive 4-week multicomponent psychotherapy outpatient eating disorders program. Response to treatment was rated on a 4-point clinical scale. Patients with marked improvement were significantly less likely to have a personality disorder diagnosis. They were also less likely to have a history of a major restrictive phase, a very low percent ideal body weight, and menstrual dysfunction.