Digit length pattern in schizophrenia suggests disturbed prenatal hemispheric lateralization.

The differentiation of the human brain is triggered by sexual steroid hormones in the fetus. The development of both the urogenital system and the appendicular skeleton are under common control by the HOX genes. Generally men have longer ring fingers than index fingers, whereas in women these fingers are close to equal. The inborn digit pattern may reflect fetal estrogen/androgen influences on hemispheric brain specialization. Reduced hemispheric asymmetry has been found in schizophrenia. Gender differences in schizophrenia also suggest a possible endocrine component in the complex pathogenesis of the illness. To test this hypothesis the authors have measured the relative digit lengths of patients with schizophrenia and healthy comparison subjects. The distance of the tip of the index and ring finger was measured from the tip of the third digit in 80 male and 80 female, right-handed patients with DSM-IV diagnosis of schizophrenia and in 80 right-handed healthy comparison men and women. Schizophrenic men and women showed a more "feminine" phenotype of the index and ring fingers in both hands than same-sex controls. This finding implies that low fetal androgen/estrogen ratio may have a predisposing role in the development of schizophrenia and points toward involvement of endocrine factors in the disturbed hemispheric lateralization attributed to the illness.

Lifetime patterns of depressive symptoms in the community and among primary care attenders: an application of grade of membership analysis.

The objective of this study was to describe empirical and natural lifetime patterns of depressive and anxiety symptoms reported by community respondents and primary care attenders. The Grade of Membership model was used to analyze data collected from 716 subjects between 18 and 64 years of age with a lifetime diagnosis of DIS/DSM-III-R Major Depressive Episode. Symptoms of depression, mania, and anxiety (GAD, panic attack, and phobias) were processed. Six prototype categories (pure types) provided the best description of the structure of symptoms included in the analysis. Type I: bipolar depression with marked suicidal behaviour, comorbidity and early onset. Type II: non-melancholic-somatisation depression with late onset. Type III: non-melancholic, non-severe bipolar depression with male preponderance. Type IV: depression secondary to anxiety with marked female preponderance. Type V: melancholic depression with suicide ideation. Type VI: melancholic depression with panic attacks and female preponderance. The results support the heterogeneity of the longitudinal symptom pattern of depression and the existence of two time-trend types of comorbid anxiety disorders.

Blunted prolactin response to fentanyl in depression. Normalizing effect of partial sleep deprivation.

There is some evidence that sleep deprivation (SD) might exert its antidepressant properties by involving endogenous opioid mechanisms. The authors investigated the effects of mu-receptor agonist administration on prolactin release in depressed patients before and after partial SD. Medication-free female depressed inpatients (N=18) were participating in two fentanyl challenge tests after partial SD and undisturbed sleep, 3 days apart in random order. Healthy volunteer women (N=10) were enrolled after full night sleep as comparison subjects. Five of them had placebo trials. Participants were given an intravenous injection of 0.1 mg/70 kg fentanyl at 9:00 AM. The prolactin secretory response to the opiate agonist was investigated for 1 h with serial blood sampling. After a night of undisturbed sleep, fentanyl administration prompted increases in plasma prolactin concentrations with blunted responses found in the depressed group. Following partial SD, the stimulated prolactin secretion of depressed patients increased significantly and was comparable to the response of comparison subjects. These findings suggest that SD acts via an opioid/dopamine-related mechanism. An alternative explanation, based on serotonin involvement is addressed in the discussion.

Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder.

OBJECTIVE: To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder. METHOD: Outpatients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were randomized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline, in daily doses of 50 to 100 mg, or imipramine, in daily doses of 100 to 200 mg. Primary outcome measures were panic attack frequency (derived from patient diaries) and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: 138 patients were treated with sertraline (76% female; mean age = 40 years) and 69 with imipramine (70% female; mean age = 40 years). The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs. Endpoint improvement with sertraline versus imipramine, respectively, on the MADRS was 11.1 +/- 10.8 versus 11.2 +/- 10.4, and on the Clinical Global Impressions-Improvement scale (CGI-I) was 2.1 +/- 1.3 versus 2.4 +/- 1.6. Among study completers, CGI-I responder rates were 88% with sertraline and 91% with imipramine. Treatment outcome was concordant for both diagnoses in approximately 70% of patients and discordant in approximately 30%. Overall, sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events (11% vs. 22%; chi(2) = 4.39, df = 1, p =.04). CONCLUSION: Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder, with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine.

Opiate sensitivity test in patients with stereotypic movement disorder and trichotillomania.

Preliminary data about the therapeutic effect of opiate receptor manipulation in self-injurious behavior (SIB) suggest that endogenous opioid mechanisms may have a pathophysiological role in that condition and their involvement may be dependent on the severity of the SIB. The aim of this study was to use fentanyl-induced prolactin response as an opiate receptor sensitivity test in patients with stereotypic movement disorder (SMD) manifesting SIB (skin picking). Healthy volunteers and trichotillomanic patients were enrolled as comparison subjects. Individuals with trichotillomania (TTM) manifest repetitive, less serious self-mutilation (hair pulling) and are classified under different DSM-IV category than SMD. Therefore, they were considered as patient controls. Ten healthy subjects received 0.05 mg/70 kg and another 10 were given 0.1 mg/70 kg dose of fentanyl intravenously in the AM hours. Five of them had placebo trials. A dose of 0.05 mg/70 kg fentanyl was administered to patients with SMD (n = 10) and TTM (n = 12). Serial blood sampling was performed for prolactin measurements. Fentanyl elevated plasma prolactin in a dose-dependent manner. Patients with skin picking, but not with hair pulling, showed significantly increased responses. This finding supports the involvement of endogenous opioids in the pathomechanism of serious SIB.

Gender difference in m-CPP challenge test in healthy volunteers.

Challenge test with oral m-CPP and placebo were performed in 12 healthy, young volunteers (6 male, 6 female) in a double-blind, placebo-controlled, cross-over study to assess possible gender differences in serotonergic responsivity. Women but not men showed significant prolactin and anxiety increase after administration of 0.25 mg/kg oral m-CPPP. Core temperature increased in both sexes compared to placebo. m-CPP induced significant physical symptoms only in men. Gender differences in serotonergic functions may have clinical significance with regard to differences in rates of some psychiatric disorders between the sexes.

Prolactin Response to Pentylenetetrazol (Cardiazol) Convulsive Therapy.

Epileptic grand mal seizures as well as electroconvulsive therapy (ECT) induce a transient robust prolactin hypersecretion. Similar prolactin response has been demonstrated following pentylenetetrazol (Cardiazol)-induced seizures in two schizophrenic female patients. A slight increase in cortisol secretion but no change in thyroid stimulating hormone and growth hormone levels suggest that the prolactin response is a specific hormonal change during convulsive treatments.