Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD.

The efficacy of selective serotonin reuptake inhibitors (SRIs) in psychiatric disorders may be "augmented" through the addition of atypical antipsychotic drugs. A synergistic increase in dopamine (DA) release in the prefrontal cortex has been suggested to underlie this augmentation effect, though the mechanism of action is not clear yet. We used in vivo microdialysis in rats to study DA release following the administration of combinations of fluvoxamine (10 mg/kg) and quetiapine (10 mg/kg) with various monoamine-related drugs.

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.

Neuroendocrine and immune responses to a cognitive stress challenge in veterans with and without PTSD.

Background: PTSD has been associated with altered hypothalamus-pituitary-adrenal-axis (HPA-axis), immune and sympathetic nervous system (SNS) regulation. The purpose of this study was to evaluate the effect of cognitive stress on these systems in PTSD patients and controls.

Methods: The subjective units of distress score (SUDS), NK-cell response, plasma levels of noradrenalin and ACTH in response to cognitive stress were assessed in male veterans with PTSD (n=15) and age, region and year of deployment matched veterans without psychopathology (n=15).

Sympathetic activity and hypothalamo-pituitary-adrenal axis activity during sleep in post-traumatic stress disorder: a study assessing polysomnography with simultaneous blood sampling.

Background: Nightmares and insomnia in PTSD are hallmark symptoms, yet poorly understood in comparison to the advances toward a biological framework for the disorder. According to polysomnography (PSG), only minor changes in sleep architecture were described. This warrants alternative methods for assessing sleep regulation in PTSD.

Wireless implantable micro-stimulation device for high frequency bilateral deep brain stimulation in freely moving mice.

Although deep brain stimulation (DBS) has been proven to be an effective treatment for several neuropsychiatric disorders, such as Parkinson's disease, the underlying working mechanisms are still largely unknown. Behavioral animal models are essential in examining the working mechanisms of DBS and especially mouse models are necessary to investigate the genetic component underlying specific behaviors related to psychiatric diseases. Unfortunately, currently available stimulation devices are unsuitable to test behavior in freely-moving mice.

Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour.

Catechol-O-methyltranferase gene expression is associated with response to citalopram in obsessive-compulsive disorder.

Objective: To determine whether polymorphisms of the dopamine D(2) receptor (DRD2) and catechol-O-methyl-transferase (COMT) receptor genes affect the efficacy of quetiapine addition to citalopram in patients with OCD.

Methods: Sixty-four drug-free or drug-naïve patients meeting DSM-IV criteria for OCD were randomized to 10 weeks double-blind treatment with citalopram (60 mg/day) with quetiapine (300 -450 mg/day) or with placebo. The change from baseline to endpoint on the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the response to treatment were the primary outcome measures.

Marked inbred mouse strain difference in the expression of quinpirole induced compulsive like behavior based on behavioral pattern analysis.

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder with a lifetime prevalence of 2-3%. Recent work has shown that OCD rituals were not only characterized by a high rate of repetition but also by an increased behavioral repertoire due to additional non-functional unique acts. These two behavioral characteristics may provide an ethological basis for studying compulsive behavior in an animal model of OCD.

Paroxetine augmentation in patients with generalised social anxiety disorder, non-responsive to mirtazapine or placebo.

Objectives: The aim of the study was to investigate if combination of mirtazapine with paroxetine causes a greater therapeutic effect and less sexual side effects than paroxetine monotherapy in social anxiety disorder (SAD).

Methods: Twenty one patients with generalised SAD, non-responsive to a 12 week trial with mirtazapine and 22 patients, non-responsive to placebo received paroxetine (20-40 mg) in addition to their double-blind treatment with mirtazapine or placebo for another 12 weeks. The Liebowitz Social Anxiety Scale (LSAS) and the Clinical Global Impression-Improvement (CGI-I) scale were used to measure efficacy.

Obstructive sleep apnea in combat-related posttraumatic stress disorder: a controlled polysomnography study.

Background: Obstructive sleep apnea (OSA) may be highly prevalent in posttraumatic stress disorder (PTSD) and may exacerbate PTSD complaints.

Objective: Our objective was to determine whether the prevalence of OSA was high in a sample of Dutch veterans with PTSD as compared to age- and trauma-matched controls, and whether OSA was associated with more severe PTSD complaints.

Methods: We determined the apnea hypopnea indices (AHI) with polysomnographic registrations in 20 veterans with PTSD, 24 veterans without PTSD, and 17 healthy controls.

Electroconvulsive therapy has acute immunological and neuroendocrine effects in patients with major depressive disorder.

Background: Major depressive disorder is associated with alterations in the neuroendocrine as well as immune system. Few studies examined the impact of electroconvulsive therapy (ECT) on these systems in patients with major depressive disorder (MDD).

Methods: In this explorative study 12 patients suffering from medication-resistant MDD or MDD with psychotic features were studied during the first, the fifth and eleventh session of ECT.

Behavioral pattern analysis and dopamine release in quinpirole-induced repetitive behavior in rats.

Obsessive-compulsive disorder (OCD) is a chronic and disabling psychiatric disease with a lifetime prevalence of 2-3%. People with OCD suffer from intrusive, unwanted and recurrent thoughts (obsessions) and/or repetitive ritualistic behaviors (compulsions). The aim of this study is to quantify the dimensions of ritualistic 'compulsive-like' behavior in quinpirole-induced behavior in rats by using T-pattern behavioral analysis.

Mirtazapine in generalized social anxiety disorder: a randomized, double-blind, placebo-controlled study.

This study is aimed at investigating the efficacy and tolerability of mirtazapine in a generalized social anxiety disorder. Sixty patients with generalized social anxiety disorder were randomly allocated to receive mirtazapine (30-45 mg/day) (n= 30) or placebo (n= 30) for 12 weeks in a double-blind study design. Primary efficacy was assessed by the Liebowitz Social Anxiety Scale (LSAS) and response to treatment was defined as a reduction of 40% on the LSAS and an improvement on the Clinical Global Impression scale of 'much or very much improved'.

Sensory gating and sensorimotor gating in medication-free obsessive-compulsive disorder patients.

Obsessive-compulsive disorder (OCD) is associated with deficits in inhibition mechanisms. This is reflected in reports showing impaired sensorimotor and sensory gating in OCD patients, as measured with prepulse inhibition (PPI) of the startle reflex and P50 suppression paradigms. However, most of the patients in these studies used medication and the results were not controlled for menstrual cycle phase in women.

Impaired neuroendocrine and immune response to acute stress in medication-naive patients with a first episode of psychosis.

Little is known about how the biological stress response systems--the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system--function during psychosis. Results of studies on the effect of stress on the immune and autonomic system in patients with schizophrenia are inconsistent. The present study investigates whether the stress response is impaired in medication-naive patients with a first episode of psychosis.

Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms.

The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors (SSRIs). In spite of the success of serotonin reuptake inhibiting drugs, nearly half of OCD patients do not respond to treatment. Treatment response may be affected by genetic polymorphisms of the P450 metabolic system.

Disgust affects TNF-alpha, IL-6 and noradrenalin levels in patients with obsessive-compulsive disorder.

Neurobiological research of obsessive-compulsive disorder (OCD) has rarely taken in account the context dependent evocation of obsessive-compulsive symptoms. To bypass this obstacle, this study investigated neurobiological parameters during a standardized disgust provocation paradigm in patients with OCD and healthy controls. Ten OCD patients and 10 healthy controls were exposed to 9 disgust related items using a standardized provocation paradigm.

Recent advances in understanding and treating social anxiety disorder.

The common occurrence and high level of morbidity and burden associated with social anxiety disorder (SAD) are gaining widespread recognition. Interest in understanding and treating the disorder has also grown in response to large-scale investigations that have demonstrated high levels of efficacy with both pharmacologic and nonpharmacologic treatments. Such trials indicate that many patients with generalized SAD (roughly 40% to 60%) respond (eg, Clinical Global Impressions-Improvement rating 1 or 2) after an adequate treatment trial, despite having suffered with disabling symptoms for most of their adult lives.

Compulsivity in mouse strains homologous with chromosomes 7p and 15q linked to obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe anxiety disorder characterized by obsessions and compulsions. The core symptom of OCD is compulsivity, the inability to stop thinking or acting when you want to, despite being aware of the uselessness of the content or the adverse consequences. To initiate a systematic search for genetic mechanisms underlying the pathophysiology of compulsivity, a panel of chromosome substitution (CS) strains, derived from mice that suppress (C57BL/6J strain) or maintain (A/J strain) high levels of repetitive wheel running during 2 hr of daily limited food access, was screened for this compulsive behavior.

Quetiapine augments the effect of citalopram in non-refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled study of 76 patients.

Objective: To assess the efficacy of quetiapine addition to citalopram in treatment-naive or medication-free obsessive-compulsive disorder (OCD) patients.

Method: Seventy-six patients who met DSM-IV criteria for OCD and who were drug-free or drug-naive at entry were randomly assigned in a 10-week, double-blind trial with citalopram (60 mg/day) plus quetiapine (300-450 mg/day) or placebo; treatment-refractory OCD patients were excluded. Of the 76 eligible patients, 66 patients completed the trial-31 in the quetiapine and 35 in the placebo group.

Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude.

Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors.

Neuropsychological performance is related to current social and occupational functioning in veterans with posttraumatic stress disorder.

Background: Several studies have reported deficits in both immediate and delayed recall of verbal memory in patients with posttraumatic stress disorder (PTSD). However, most of these studies had several methodological disadvantages. None of these studies assessed parameters related to social or occupational functioning.

Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-treatment with ritanserin and placebo.

Introduction: Several studies in obsessive compulsive disorder (OCD) have provided circumstantial evidence that the 5-HT-system is involved in the pathophysiology of OCD. To further examine the role of 5-HT receptors we studied the behavioural and neuroendocrine effects of different doses of meta-chlorophenylpiperazine (mCPP) in OCD patients and healthy controls, after pre-treatment with ritanserin, a 5-HT2 receptor antagonist, and placebo.

Design: Twenty patients and 20 healthy controls received 0.

Thinner prefrontal cortex in veterans with posttraumatic stress disorder.

Structural neuroimaging studies in posttraumatic stress disorder (PTSD) have focused primarily on structural alterations in the medial temporal lobe, and only a few have examined grey matter reductions in the cortex. Recent advances in computational analysis provide new opportunities to use semi-automatic techniques to determine cortical thickness, but these techniques have not yet been applied in PTSD. Twenty-five male veterans with PTSD and twenty-five male veterans without PTSD matched for age, year and region of deployment were recruited.