Michael A. Schlesser

A controlled study of cellular immune function in affective disorders before and during somatic therapy

Lymphocyte blastogenesis induced by lectins (PHA, Con A, and PWM) was assessed in 27 drug-free patients with unipolar (n = 21) or bipolar (n = 5) depression and 13 normal controls. Fifteen patients were restudied after clinical remission. Symptomatic patients did not differ from controls nor did endogenous and nonendogenous depressions differ in their lymphocyte blastogenesis response to any of the three lectins. However, a significant reduction in lymphocyte blastogenesis with both PHA and Con A stimulation was found following somatic treatment. Cellular immune function appears to be normal in depressed patients, although the somatic therapies are associated with a reduction in this function.

TRH-induced prolactin release is blunted in females with endogenous unipolar major depression.

Twenty-five women with unipolar primary major depressive disorder (20 endogenous, 5 nonendogenous) and 20 female control subjects were studied with the thyrotropin-releasing hormone stimulation test (TRH-ST). Prolactin (PRL) levels were measured before and after TRH administration for patients and control subjects. For patients, thyrotropin (thyroid-stimulating hormone; TSH) levels were measured from the same serum specimens as PRL levels, and the 1 mg dexamethasone suppression test (DST) was performed. Patients with endogenous depression (ED) had significantly lower maximal serum PRL levels (max PRL) following TRH, and a significantly reduced increase over basal serum PRL (delta max PRL) compared to normal controls (NC). Nonendogenous depressed (NED) patients did not differ significantly from the ED or NC groups on either of these measures. For the ED group, delta max PRL was inversely correlated with severity of depressive symptomatology. Basal PRL levels did not differentiate the depressed subgroups (ED, NED) from each other or from the NC group. Depressed patients with blunted delta max PRL values tended to have blunted delta max TSH values and vice versa. Almost all patients with blunting of either delta max PRL or delta max TSH were also DST nonsuppressors; conversely, only about half (7 of 12) of patients who were DST nonsuppressors had either blunted delta max PRL or delta max TSH. Patients with clinical diagnoses of melancholia or psychotic features were significantly more likely to have blunted delta max PRL values than patients without these diagnoses. A disturbance of central noradrenergic function could explain these findings.

Free triiodothyronine (T3) and thyroxine (T4) in a group of unipolar depressed patients and normal subjects

We examined levels of free triiodothyronine (fT3) and free thyroxine (fT4) in serum from a group of 32 patients with unipolar major depression and 46 normal control subjects using the Amerlex (Amersham, Arlington Heights, IL) RIA procedures for these hormones. Free T3 levels were significantly lower (p less than 0.004) in the depressed patients as a group (5.02 +/- 1.01 pmol/L, mean +/- SD) than in the normal control subjects (5.74 +/- 1.23 pmol/L). Free T3 levels were lower (p less than 0.01) in depressed men (5.25 +/- 1.43 pmol/L) when compared with male control subjects (6.46 +/- 1.01 pmol/L). Depressed women (4.78 +/- 0.60 pmol/L) also had lower T3 levels than did the female control subjects (5.09 +/- 1.06 pmol/L), but the difference was not statistically significant. Lower fT3 levels were also observed in melancholic depressed patients when compared with nonmelancholic depressed patients or when compared with normal control subjects. No differences in fT4 were observed between groups in this study.

The thyrotropin-releasing hormone stimulation test: A methodological study

Abstract Repeated thyroid-stimulating hormone (TSH) determinations were carried out for 90 or 180 minutes following thyrotropin releasing hormone (TRH) stimulation in 160 euthyroid psychiatric patients, most of whom had a symptomatic affective disorder. The purpose was to determine which of the simple TSH measurements from the TRH stimulation test (TRH-ST) yield(s) the most accurate index of pituitary TSH reserves and to clarify the relationship between the various TRH-ST methods reported in the literature. The area beneath the 180 minute TSH response curve, the best available parameter of pituitary TSH stores, was calculated and compared to simple indices of absolute TSH level and increase from 0 minute baseline. Fourteen parameters of the TSH response were determined; TSH 0, TSH 15, TSH 30, and TSH 45 represent the absolute levels at 0, 15, 30, and 45 minutes after TRH administration, respectively. TSH Max is the maximum TSH level attained after TRH infusion among all TSH measures. Δ TSH measures are the increase in TSH relative to baseline. The Δ Max TSH and Δ TSH 30 were highly correlated with the ideal index of pituitary TSH reserve (0 – 180 minute area). Subjects were classified as either blunted or normal over a broad range of Δ Max TSH criteria or thresholds. The number of misclassified subjects (false positives) at each criterion was counted for each of the seven possible combinations of Δ TSH 15, Δ TSH 30, and/or Δ TSH 45. The simplest index which produced the smallest number of false positives was Δ TSH 30 whereas Δ Max TSH (15, 30, and 45) produced no false positives. Overall, Δ TSH 30 was a very good simple index of pituitary TSH stores. This may be the preferred index when economy of time, expense, or blood samples is desired. However, it results in 5–7% false positives, which will compromise specificity somewhat. The preferred simple index of pituitary TSH reserves when accuracy is of highest priority is Δ Max TSH (15, 30, and 45). These data reveal that the TRH-ST can be simplified to include only four TSH levels: TSH 0, TSH 15, TSH 30, and TSH 45.

Dexamethasone Suppression, Protirelin Stimulation, and Insulin Infusion in Subtypes of Recovered Depressive Patients

Twenty-eight patients (10 bipolar, 13 depressive spectrum disease, and 5 familial pure depressive), recovered from depression for an average of 1 year, underwent a series of basal and provocative endocrine tests. No significant differences were found among depressive subtypes in thyrotropin, cortisol, or growth hormone measurements either before or after provocative testing with the exception of growth hormone response to insulin-induced hypoglycemia. Patients with depressive spectrum disease showed a significantly different growth hormone response to insulin-induced hypoglycemia than patients with bipolar disorder, a finding which suggests differences in alpha-adrenergic receptor sensitivity between these groups.