Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats.

The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced "maternal" behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of "maternal" behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups. The present findings provide evidence that prenatal environmental stress can "demasculinize" the behavior, brain anatomy and hormone secretion in the male fetuses expressed when they reach maturity. Moreover, the nature of the maternal care received by neonates can affect the behavior and physiology that they express at maturity.

Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder.

BACKGROUND: Transcranial magnetic stimulation (TMS) was introduced as a neurophysiological technique in 1985 when Anthony Barker and his team developed a compact machine that permitted non-invasive stimulation of the cerebral cortex (Barker 1985). Since its introduction, TMS has been used to evaluate the motor system, to study the function of several cerebral regions, and for the pathophysiology of several neuropsychiatric illnesses. In addition, it has been suggested that TMS might have therapeutic potential. Some controlled studies have evaluated the effects of repetitive TMS (rTMS) in patients with obsessive-compulsive disorder (OCD). Greenberg (Greenberg 1997) observed that a single session of right prefrontal cortex stimulation produced a significant decrease in compulsive urges in OCD patients lasting over eight hours. Other studies have reported transitory improvements in mood but there are no observations for changes in anxiety or obsessions. OBJECTIVES: To develop a systematic review on the clinical efficacy and safety of transcranial magnetic stimulation from randomised controlled trials in the treatment of obsessive-compulsive disorder. SEARCH STRATEGY: An electronic search was performed including the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group trials register (last searched June, 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966-2002), EMBASE (1974-2002), PsycLIT (1980-2002), and bibliographies from reviewed articles. SELECTION CRITERIA: Randomised controlled trials assessing the therapeutic efficacy and safety of transcranial magnetic stimulation for obsessive-compulsive disorder. DATA COLLECTION AND ANALYSIS: All reviewers independently extracted the information and verified it by cross-checking. Disagreements were resolved through discussion. MAIN RESULTS: Three trials were included in the review and only two contained data in a suitable form for quantitative analysis. It was not possible to pool any results for a meta-analysis. No difference was seen between rTMS and sham TMS using the Yale-Brown Obsessive-Compulsive Scale or the Hamilton Depression Rating Scale for all time periods analysed. REVIEWER'S CONCLUSIONS: There are currently insufficient data from randomised controlled trials to draw any conclusions about the efficacy of transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder.

Role of 3.0 T multiparametric MRI in local staging in prostate cancer and clinical implications for radiation oncology.

PURPOSE: To evaluate the accuracy of preoperative 3T multiparametric magnetic resonance imaging (3TmMRI) for local staging of prostate cancer and its influence on the decision to change the clinical target volume (CTV), total dose and hormonal therapy when treating prostate cancer patients with radiotherapy. METHODS: From 2009 to 2013, 150 patients, who had confirmed prostate cancer and underwent a 3TmMRI before treatment with radical prostatectomy or radical radiation therapy, were included. Radiation therapy treatment (CTV, total dose and hormonal therapy) was initially determined on the basis of the clinical information, and radiation therapy plan was reevaluated after 3TmMRI review. The value of preoperative 3TmMRI in local staging and in the decision of radiotherapy treatment according to NCCN risk classification was analyzed. RESULTS: 3TmMRI performed correct, over- and under staging in 78.7 % (37/47), 6.3 % (3/47), 14.8 % patients (7/47), respectively. 3TmMRI identified 6 cT2a, 7 cT2b, 28 cT2c, 3 cT3a, 3 cT3b tumors. At final pathology, 5 tumors were classified as pT2a, 5 as pT2b, 30 as pT2c, 4 as pT3a, 3 as pT3b. After reviewing the MRI reports, the initial radiotherapy and hormonal therapy plan was changed in 33.9 % patients (35/103). CONCLUSIONS: In our group of patients, 3TmMRI has been a reliable technique providing an optimal staging for prostate cancer. Its routine use could induce important changes in radiation therapy treatments in a significant number of such patients. However, more additional studies are needed to clarify this issue.

Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs.

PURPOSE: To determine the efficacy of vagus nerve stimulation (VNS) for treatment of depression. METHODS: We conducted a systematic review and meta-analysis of analytical studies. Efficacy was evaluated according to severity of illness and percentage of responders. RESULTS: We identified 687 references. Of these, 14 met the selection criteria and were included in the review. The meta-analysis of efficacy for uncontrolled studies showed a significant reduction in scores at the Hamilton Depression Rating Scale endpoint, and the percentage of responders was 31.8% ([23.2% to 41.8%], P<0.001). However, the randomised control trial which covered a sample of 235 patients with depression, reported no statistically significant differences between the active intervention and placebo groups (OR=1.61 [95%CI 0.72 to 3.62]; P=0.25). To study the cause of this heterogeneity, a meta-regression was performed. The adjusted coefficient of determination (R2(Adj)) was 0.84, which implies that an 84% variation in effect size across the studies was explained by baseline severity of depression (P<0.0001). CONCLUSION: Currently, insufficient data are available to describe VNS as effective in the treatment of depression. In addition, it cannot be ruled out that the positive results observed in the uncontrolled studies might have been mainly due to a placebo effect.

Maternal care counteracts behavioral effects of prenatal environmental stress in female rats.

There is extensive evidence in rats that prenatal environmental stress (PES) exposure and early postnatal altered maternal care, as a consequence of stress during gestation, can detrimentally affect the brain and behavioral development of the offspring. In order to separate the effect of PES on the fetuses from that on the behavior of the mother, in the present study, we used a cross-fostering procedure in which PES-fetuses were raised by non-stressed mothers and non PES-fetuses were raised by stressed mothers. In Experiment 1, non-stressed mothers showed significantly more maternal behavior than stressed mothers. In Experiment 2, when the female offspring from Experiment 1 reached maturity, they were tested for: (1) induced maternal behavior (MB), (2) plasma levels of corticosterone (Cpd B), progesterone (P), and estradiol (E(2)), (3) number of accessory olfactory bulb (AOB) mitral cells, and (4) c-fos expression measured in AOB and medial preoptic area (MPOA) neurons. We replicated our previous findings that the PES group reared by their own stressed mothers, when adult, attacked the young, expressed disorganized MB and showed altered Cpd B, P and E(2) levels, plus a male-like neuro-morphological pattern in the AOB, by comparison with the non-PES group, reared by their own non-stressed mothers. By contrast, when adult, the PES group reared by non-stressed mothers showed hormonal and morphological neuronal alterations, but they displayed appropriate (full) MB. The non-PES group raised by stressed mothers also showed altered hormone levels, but showed full MB and no morphological neuronal changes. Significant differences in the AOB and MPOA c-fos activity, related to whether or not MB was expressed, were found in the non-PES groups, but not in the PES group reared by non-stressed mothers. To our knowledge, this is the first study to document that adequate maternal care, early in development, can shape the subsequent expression of induced MB, overcoming neuro-morphological and hormonal alterations that are produced by prenatal environmental stress. We conclude that maternal care during early postnatal development can counteract detrimental effects of prenatal environmental stress, exerting long-lasting effects that modulate the behavioral phenotype of the offspring.

Olanzapine orally-disintegrating tablet in severe psychotic agitation: a naturalistic study.

INTRODUCTION: This study was conducted to determine effectiveness and safety of olanzapine in patients with severe agitation. METHOD: A naturalistic, open-label study in 80 acutely agitated psychotic patients visited in our psychiatric emergency department. Patients received either a 20-mg olanzapine orally-disintegrating tablet or conventional treatment depending on attending psychiatrist's preference. Efficacy was assessed by the Excitement Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale (ACES) and pragmatic variables (second pharmacological intervention and need for physical restraints). RESULTS: 60 % patients completed a 6 hour trial. Both groups showed a significant reduction in mean PANSS-EC score. The olanzapine-treated group showed statistically significant improvements: PANSS-EC (F=122.9; df=2.4; p=0.000), ACES (F=68.2; df=2.8; p=0.000). Treatment was well-tolerated and no serious side-effects were observed. CONCLUSIONS: In this naturalistic study in patients with severe agitation, 20-mg oral olanzapine was effective, rapid and safe.