Panic disorder and locomotor activity

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Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD.</p> <p>Methods</p> <p>A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse.</p> <p>Results</p> <p>The severities of early (<it>P </it>> 0.05), middle (<it>P </it>> 0.05), late (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (<it>P </it>> 0.05), oversleeping (<it>P </it>> 0.05), napping (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment.</p> <p>Conclusion</p> <p>The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00427128</p

Automatic mapping of atoms across both simple and complex chemical reactions

Mapping atoms across chemical reactions is important for substructure searches, automatic extraction of reaction rules, identification of metabolic pathways, and more. Unfortunately, the existing mapping algorithms can deal adequately only with relatively simple reactions but not those in which expert chemists would benefit from computer&apos;s help. Here we report how a combination of algorithmics and expert chemical knowledge significantly improves the performance of atom mapping, allowing the machine to deal with even the most mechanistically complex chemical and biochemical transformations. The key feature of our approach is the use of few but judiciously chosen reaction templates that are used to generate plausible &quot;intermediate&quot; atom assignments which then guide a graph-theoretical algorithm towards the chemically correct isomorphic mappings. The algorithm performs significantly better than the available state-of-the-art reaction mappers, suggesting its uses in database curation, mechanism assignments, and - above all - machine extraction of reaction rules underlying modern synthesis-planning programs

Dissection of Hypothalamic-Pituitary-Adrenal Axis Pathology in 1-Month-Abstinent Alcohol-Dependent Men, Part 2: Response to Ovine Corticotropin-Releasing Factor and Naloxone

Pituitary and adrenal responsiveness is suppressed in abstinent alcohol-dependent individuals. To clarify the specific organizational disruption in hypothalamic-pituitary-adrenal functioning during early abstinence, the authors separately assessed each level of the stress-response axis. In this second of a two-part study, ovine corticotropin-releasing factor (oCRH) was used to stimulate the pituitary corticotrophs, and naloxone was used to activate the axis at the hypothalamic level. In addition, pulsatile characteristics of corticotropin and cortisol were assessed over a 12-hr period (0800 to 2000 hr). Methods : Eleven abstinent alcohol-dependent men and 10 healthy comparison participants were assessed. All participants were between the ages of 30 and 50 years, and alcohol-dependent patients were abstinent from 4 to 6 weeks. Basal concentrations of corticotropin and cortisol were obtained every 10 min from 0800 to 2000 hr and subjected to pulsatile analysis. Plasma corticotropin and cortisol concentrations were then obtained every 5 to 10 min after low-dose, intravenously administered doses of oCRH (0.4 μg/kg) or naloxone (0.125 mg/kg). Medications were administered at 2000 hr and the two challenge studies were separated by 48 hr. Results : Pulsatile analysis revealed that the mean corticotropin amplitude was increased in alcohol-dependent patients relative to controls ( p < 0.05). Other pulsatile characteristics of corticotropin and all cortisol pulsatile measures were not significantly different between the two groups. The integrated cortisol response to oCRH was significantly lower in alcohol-dependent patients compared with controls ( p < 0.01), but the integrated corticotropin response was not significantly different. In contrast, neither the corticotropin nor the cortisol response to naloxone was significantly different between groups. Conclusions : Adrenocorticoid hyposensitivity persists after oCRH infusion for at least 1 month after cessation of drinking, whereas hyporesponsiveness of the pituitary corticotrophs to CRH seems to resolve with continued abstinence. The authors suggest that adrenocortical hyporesponsiveness during prolonged abstinence may impact relapse risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65174/1/01.ALC.0000158939.25531.EE.pd

Disproportionate Alterations in the Anterior and Posterior Insular Cortices in Obsessive–Compulsive Disorder

Recent studies have reported that the insular cortex is involved in the pathophysiology of obsessive–compulsive disorder (OCD). However, specific morphometric abnormalities of the insular subregions remain unclear. In this study, we examined insular cortical volume to determine whether the volume of the anterior and posterior insular cortices of unmedicated OCD patients differed according to different symptom dimensions.Using magnetic resonance imaging, we measured the gray matter volumes of the insular cortex and its subregions (anterior and posterior divisions) in 41 patients with OCD (31 drug-naïve and 10 non-medicated) and 53 healthy controls. Volumetric measures of the insular cortex were compared according to different OC symptoms. Enlarged anterior and reduced posterior insular cortices were observed in OCD patients. The insular volumetric alterations were more significant in OCD patients with predominant checking rather than cleaning symptoms when compared with healthy controls.Our results suggest the presence of unbalanced anterior and posterior insular volumetric abnormalities in unmedicated OCD patients and emphasize the distinct role of the insular cortex in different OC symptoms. We propose that the insular morphometric alterations may influence the modulation of interoceptive processing, the insular functional role, in OCD patients with different symptoms

Sensitization of catastrophic cognition in cognitive-behavioral therapy for panic disorder

<p>Abstract</p> <p>Background</p> <p>Cognitive model of panic disorder have proposed that panic attacks result from the catastrophic misinterpretation of certain bodily sensations. Cognitive-Behavioral Therapy (CBT) for panic disorder aims to change these catastrophic cognitions. CBT intervention successfully caused reduction of catastrophic cognitions and symptomatic improvement in the majority of cases. However there are some patients who fail to modify their catastrophic cognitions or rather experience an increase in them during CBT treatment. It is clinically and theoretically important to understand about cognitive sensitization of panic disorder during CBT sessions. The purpose of the present study is 1) to clarify the baseline characteristics of panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment, and 2) to examine the course of symptomatic changes for them.</p> <p>Methods</p> <p>Of ninety-five outpatients with panic disorder started the group CBT program for treatment of panic disorder, seventy-nine completer were classified as "cognitively sensitized (CS)" or "cognitive responding (CR)" or "no-responder" according to the difference of the Agoraphobic Cognitions Questionnaire score across treatment. We compared the CS and CR patients in terms of their baseline clinical characteristics. Then we assessed the symptomatic and functional changes for both groups.</p> <p>Results</p> <p>At the start of the CBT program, despite of the same degree of panic disorder severity, CS scored significantly lower on ACQ score than CR. CS also showed significantly lower score on anticipatory anxiety compared to CR. At the end of treatment CS showed significant improvement in severity of panic disorder, although the degree of improvement was smaller than that for CR. Then CS would progressively reduce their agoraphobic fear and avoidance, and would improve their functional impairment up to three month of follow-up.</p> <p>Conclusion</p> <p>Panic patients who would experience sensitization of their catastrophic cognitions through the CBT treatment could nonetheless gradually improve. They showed a relatively low level of catastrophic cognition and anticipatory anxiety before starting the CBT program. We might conclude that temporary sensitization of catastrophic cognition may be necessary before improvement especially among those with initially low catastrophic body sensation fears and that we need not be concerned too much with temporary increase in catastrophic cognition in the process of CBT for panic disorder.</p

Speech Graphs Provide a Quantitative Measure of Thought Disorder in Psychosis

Background: Psychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships. Methodology/Principal Findings: To quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity. Conclusions/Significance: The results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.FINEP [01.06.1092.00]FINEPCNPq Universal [481506/2007-1]CNPq UniversalCNPqCNPqCapesCAPESad Associacao Alberto Santos Dumont para Apoio a Pesquisa (AASDAP)a'd Associacao Alberto Santos Dumont para Apoio a Pesquisa (AASDAP