Gender differences in ultradian serum levels of NGF and BDNF correlate with psychophysical traits in healthy humans.

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.00 and 20.00 hours of the day in healthy men and women, and the neurotrophins concentration was measured in the serum by ELISA. A further aim of the study was to evaluate whether or not the NGF/BDNF variations might be related to specific physiological or psychological traits as mood, feeling good and feeling rested, sexual desire and energy. Heart rate and blood pressure were also monitored at the same hours in each enrolled subject. The anxiety (STAI-T and STAI-S score) and sleeping quality were once evaluated in the morning too. We found that serum BDNF increases in men and decreases in women from morning to evening, while NGF shows a similar ultradian profile between men and women, but with higher concentrations in women. Both neurotrophins also show gender-related associations with psychophysiological variables. High NGF levels correlated with a high score for all the psychological variables in men, but with a low score in women. An inverse correlation was found between BDNF and energy and sexual desire in women, while no correlations were found in men. These data disclose that the condition of well-being (or activity/arousal status) is featured by an increasing NGF profile in men and a negative BDNF/NGF trend in women. The clinical relevance of the present data is discussed.

Effects of treatment with etizolam 0.5 mg BID on cognitive performance: a 3-week, multicenter, randomized, double-blind, placebo-controlled, two-treatment, three-period, noninferiority crossover study in patients with anxiety disorder.

BACKGROUND: Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2). This property, plus its characterization as a ligand with fewer of the adverse events typical of full agonists (impaired cognitive function, tolerance, and dependence), led to its selection for this study. OBJECTIVES: The primary aim of this study was to test for the noninferiority of etizolam 0.5 mg BID versus placebo in affecting cognitive function in patients with mild to moderate anxiety disorder of recent onset (<1 month). Anxiety measures and tolerability were also assessed. METHODS: Patients between the ages of 18 and 65 years were eligible for enrollment. This double-blind, placebo-controlled study was performed in 5 centers in Italy using a 2-treatment, 3-period crossover design. Patients were randomized to 3-week sequences of either etizolam-placebo-placebo or placebo-etizolam-etizolam. They were evaluated at 4 scheduled visits (screening and days 7, 14, and 21). Cognitive function was assessed using scores from the Wechsler Adult Intelligence Scale (WAIS) Digit Span test (total forward and backward scores and the time required to perform the test). Anxiety was measured using the Hamilton Anxiety Rating Scale (HAM-A) and the State-Trait Anxiety Inventory (STAI) for screening and to monitor adequacy of therapy. Blood pressure, heart rate, weight, and adverse events were also recorded. RESULTS: A total of 77 white patients were enrolled (mean age, 33.3 years [range, 22-60 years]; 62.3% female; mean weight, 65.2 kg). With a power of 0.80, the difference between the effects of etizolam and placebo on WAIS Digit Span performance was not significant for total score (0.102 [90% CI, -0.130 to 0.335]) or time required for completion (0.029 second [90% CI, -0.574 to 0.632]). Anxiety, as measured using the HAM-A and STAI instruments, did not differ significantly between groups. No significant differences were found between etizolam 0.5 mg BID and placebo for cardiovascular events, weight changes, or adverse events. Mild or moderate somnolence was reported by 7 of 77 patients (9.1% [3 patients while receiving etizolam and 4 patients while receiving etizolam and placebo]). CONCLUSIONS: No significant differences between etizolam 0.5 mg BID and placebo were found for cognitive function or anxiety measures in these patients with anxiety. Etizolam was well tolerated.

Nicotine augmentation for refractory obsessive-compulsive disorder. A case report.

The authors present a case of obsessive-compulsive disorder (OCD) resistant to conventional treatments, which improved following nicotine augmentation administered as 4 mg chewing gum. The role of acetylcholine in the pathophysiology of OCD is not clear. The authors discuss the effect of nicotine on memory for actions.

Reduction of night/day difference in melatonin blood levels as a possible disease-related index in schizophrenia.

OBJECTIVE: Aim of this study was to verify if a simple index as night-day plasma MLT level variation is able to confirm the existing data on circadian melatonin alterations in schizophrenia and if a relationship to disease itself instead of the actual clinical state can be suggested. SETTING AND DESIGN: Ten consecutively admitted male schizophrenic inpatients were examined. METHODS: The blood samples for melatonin were collected at 3.00 a.m. and 15.00 p.m. and consequently calculated the values of Delta () (MLT h.3.00- MLT h.15.00). We divided the sample into two subgroups: < 30 pg/ml and > 30 pg/ml taking 30 pg/ml as an arbitrary value, based on literature data, that should indicate a physiologically correct value of. RESULTS: The 70% of the sample was under the 30 pg/ml value of (13.61 +/- 4.0) or was lacking of the characteristic circadian pattern of MLT secretion, whilst the 30% of the sample was over the 30 pg/ml value of (83.60 +/- 16.34) or was in presence of the characteristic circadian pattern of MLT secretion (p=.0001). No correlation was found between values and the scale and subscales scores for the assessment of psychopathology. MAIN FINDINGS: The data confirm the lack of the characteristic circadian pattern of MLT secretion in schizophrenics. CONCLUSION: The absence of significant correlation between night / day melatonin level differences and actual psychopathology variables should indicate that the suppression of is mostly related to the disease and independent from the clinical state. A neuroleptic-treatment effect cannot be excluded so far.

Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness.

Several investigations have suggested pineal gland abnormalities in the pathogenesis of schizophrenia. The pineal volume on brain magnetic resonance imaging scans was calculated in 15 male schizophrenic inpatients and in 16 matched control subjects. The statistical comparison found a significant difference of pineal gland volume between schizophrenics and controls (P = 0.022), with a smaller pineal volume in the schizophrenics. These results do not confirm the previous data of Schizophrenia Res. 14 (1995) 253, showing no significant pineal volumetric differences between schizophrenics and normal controls. Since the present study is based on a smaller but more homogeneous sample of patients, this could reduce the heterogeneity features of the schizophrenic disease. No correlation was found between pineal volume and clinical and psychopathological features of the schizophrenic subjects. Volume reduction in schizophrenia could be at least partially included in the wider brain developmental abnormalities of the illness or in the late effects of previous neuroleptic treatments.