Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial.

Cannabidiol (CBD), a principal phytocannabinoid constituent, has demonstrated antipsychotic properties in recent clinical trials. While it has also been suggested a promising candidate for the treatment of neurodegenerative disorders, it failed to demonstrate efficacy in cognitive impairments associated with schizophrenia as an add-on treatment (600 mg/day for 6 weeks) in 18 chronically ill patients co-treated with a variety of psychopharmacologic drugs. Here, we report on the results of parallel-group, active-controlled, mono-therapeutic, double-blind, randomized clinical trial (CBD-CT1; ClinicalTrials.gov identifier: NCT00628290) in 42 acute paranoid schizophrenic patients receiving either CBD (up to 800 mg/day) or amisulpride (AMI, up to 800 mg/day) for four weeks in an inpatient setting with neurocognition as a secondary objective. Twentynine patients (15 and 14 in the CBD and AMI group, respectively) completed two cognitive assessments at baseline and the end of the treatment period. We investigated the following cognitive domains: pattern recognition, attention, working memory, verbal and visual memory and learning, processing speed, and verbal executive functions. When applying the Bonferroni correction for multiple testing, p < 0.0004 would indicate statistical significance. There was no relevant difference in neurocognitive performance between the CBD and the AMI group at baseline, and we observed no post-treatment differences between both groups. However, we observed improvements within both groups from pre-to post-treatment (standardized differences reported as Cohen's d) in visual memory (CBD: 0.49, p = 0.015 vs. AMI: 0.63, p = 0.018) and processing speed (CBD: 0.41, p = 0.004 vs. AMI: 0.57, p = 0.023). Furthermore, CBD improved sustained attention (CBD: 0.47, p = 0.013, vs. AMI: 0.52, p = 0.085), and visuomotor coordination (CBD: 0.32, p = 0.010 vs. AMI: 0.63, p = 0.088) while AMI led to enhanced working memory performance in two different paradigms (Subject Ordered Pointing Task-AMI: 0.53, p = 0.043 vs. CBD: 0.03, p = 0.932 and Letter Number Sequencing-AMI: 0.67, p = 0.017 vs. CBD: 0.08 p = 0.755). There was no relevant correlation between changes in neurocognitive parameters and psychotic symptoms or anandamide serum levels. This study shows that both CBD and AMI improve neurocognitive functioning with comparable efficacy in young and acutely ill schizophrenia patients via an anandamide-independent mechanism.

Comparing Dimensional Models Assessing Personality Traits and Personality Pathology Among Adult ADHD and Borderline Personality Disorder.

OBJECTIVE: This pilot study was a comparison of dimensional models assessing personality traits and personality pathology in a clinical sample of adults diagnosed with ADHD and adults diagnosed with borderline personality disorder (BPD), and a nonclinical control sample of healthy adults. METHOD: Personality traits were assessed using the NEO-Personality Inventory-Revised (NEO-PI-R) and dimensional personality pathology with the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). RESULTS: Adults with ADHD and BPD produced higher Emotional Dysregulation/Neuroticism and Dissocial Behavior scores than controls. For the Extraversion/Inhibitedness scale, adults with BPD produced significantly lower scores than adults with ADHD and controls. On the Conscientiousness/Compulsivity domains, Conscientiousness scores were lower for both disorders, whereas low Compulsivity values were specific to adult ADHD. CONCLUSION: Our results suggest that patients with adult ADHD and BPD have distinguishable profiles of personality traits and personality pathology.

Neurocognitive functioning in parents of schizophrenia patients: Attentional and executive performance vary with genetic loading.

Neuropsychological deficits are candidate endophenotypes of schizophrenia which can assist to explain the neurocognitive impact of genetic risk variants. The identification of endophenotypes is often based on the familiality of these phenotypes. Several studies demonstrate neuropsychological deficits in unaffected biological relatives of schizophrenia patients without differentiating between genetic and non-genetic factors underlying these deficits. We assessed N=129 unaffected biological parents of schizophrenia patients, N=28 schizophrenia patients (paranoid subtype), and N=143 controls without a family history of schizophrenia with an extensive neuropsychological test battery. Direct comparison of N=22 parents with an ancestral history of schizophrenia (more likely carriers, MLC) and N=17 of their spouses without such a history (less likely carriers, LLC) allowed the separation of genetic and non-genetic aspects in cognition. Overall, parents showed significant deficits in neuropsychological tasks from all cognitive domains with medium effect sizes. Direct comparisons of MLC- and LLC-parents showed that attentional and executive tasks were most strongly affected by genetic loading. To conclude, unaffected parents of schizophrenia patients showed modest yet significant impairments in attention, memory, and executive functioning. In particular, attentional and executive impairments varied most strongly with genetic loading for schizophrenia, prioritising these dysfunctions for genotype-endophenotype analyses.

The essential features of personality disorder in DSM-5: the relationship between criteria A and B.

The essential features of the general criteria for personality disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are based on impairments in self and interpersonal functioning (criterion A) and pathological personality traits (criterion B). The current study investigated the relationship between criteria A and B in a German psychiatric sample (N = 149). Criterion A was measured by the General Assessment of Personality Disorder (GAPD); criterion B, by the Dimensional Assessment of Personality Pathology (DAPP) and the Revised NEO Personality Inventory (NEO-PI-R). There was a significant relationship between the GAPD, the DAPP, and the NEO-PI-R. The DAPP and NEO-PI-R domains increased the predictive validity of the GAPD (by 7.5% and 14.6%, respectively). The GAPD increased the variance explained by the DAPP by 1.5% and by the NEO-PI-R by 6.5%. The results suggest a substantial relationship between criteria A and B. Criterion B shows incremental validity over criterion A but criterion A only in part over criterion B. Future research should investigate whether it is possible to assess functional impairment apart from personality traits.

5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option.

A role of the HTR3A-E genes in obsessive-compulsive disorder (OCD) can be expected based on promising effects of 5-HT3 receptor antagonists as adjunctive treatment of OCD. We therefore genotyped six common coding or promoter variants within the HTR3A-E genes in a case-control-sample consisting of N=236 OCD patients and N=310 control subjects and in N=58 parent-child-trios. Given the heterogeneous OCD phenotype, we also investigated OCD symptom dimensions and cognitive endophenotypes in subsamples. OCD patients scoring high for the washing subtype were significantly more likely to carry the c.256G-allele of the HTR3E variant rs7627615 (p=0.0001) as compared to OCD patients low for this symptom dimension. Visual organization was impaired in OCD patients and unaffected relatives as compared to healthy control subjects and carriers of the HTR3E c.256G/c.256G-genotype performed significantly worse (p=0.007). The case-control analyses revealed a nominal significant association of the HTR3D variant rs1000592 (p.H52R) with OCD (p=0.029) which was also evident after combination of the case-control and the trio-results (p=0.024). In male subjects, the variant rs6766410 (p.N163K) located in the HTR3C was significantly associated with OCD (p=0.007). The association findings of the HTR3C and the HTR3E remained significant after correction for the number of variants investigated. These findings indicate a role of common variants of the HTR3A-E genes in OCD and OCD-related phenotypes and further support the use of 5-HT3 receptor antagonists as novel treatment options. The HTR3E gene is a novel candidate gene impacting on the individual expression of OC symptoms and OCD-related cognitive dysfunction.

The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive-compulsive disorder.

Neuropeptide S (NPS) is a novel central acting neuropeptide that modulates several brain functions. NPS has shown strong anxiolytic-like effects and interactions with other central transmitter systems, including serotonin and glutamate. A coding variation (Asn107Ile) of the NPS receptor gene (NPSR1) was associated with panic disorder and schizophrenia. Based on these encouraging findings, the present study aimed at exploring a potential role of NPSR1 in obsessive­compulsive disorder (OCD). A sample of 232 OCD patients was successfully genotyped for the NPSR1 Asn107Ile variant (rs324981). Age at onset was taken into account to address the heterogeneity of the OCD phenotype. The NPSR1 genotype significantly affected age at onset of the OCD patients, with a mean age at onset approximately 4 yr earlier in homozygous carriers of the low-functioning Asn107 variant compared to patients with at least one Ile107 variant (p=0.032). Case­control analyses with 308 healthy control subjects reveal a highly significant association of the Asn107 variant with early onset OCD (odds ratio=2.36, p=0.0004) while late onset OCD or the OCD group as a whole were unrelated to the NPSR1 genotype. Based on our association finding relating NPSR1 genotype to early onset OCD, we suggest a differential role of the NPS system in OCD. In particular, the early onset OCD subtype seems to be characterized by a genetically driven low NPS tone, which might affect other OCD-related transmitter systems, including the serotonin and glutamate systems. In agreement with preclinical research, we suggest that NPS may be a promising pharmacological candidate with anti-obsessional properties.

Antisaccade performance in patients with obsessive-compulsive disorder and unaffected relatives: further evidence for impaired response inhibition as a candidate endophenotype.

Cognitive dysfunctions such as inhibitory deficits and visuospatial abnormalities are often found in patients with obsessive-compulsive disorder (OCD). Recent findings in unaffected relatives indicate that response inhibition and other neuropsychological functions may also constitute endophenotypes of OCD. In the present study, 30 OCD patients, 30 first-degree relatives, and 30 healthy control subjects were assessed using a comprehensive neuropsychological test battery. A subsample of 21 subjects of each group also performed an antisaccade task. The samples were matched according to age, gender, education, and verbal intelligence. The OCD patients and the unaffected OCD relatives showed increased antisaccade error rates compared with the healthy control group (p = 0.003, p = 0.028, respectively). Significantly prolonged antisaccade latencies as compared to prosaccade latencies were only found in the OCD patients compared with the healthy control group (p = 0.019). Only OCD patients but not the unaffected OCD relatives were impaired with regard to visuospatial functions, problem-solving, and processing speed. Antisaccade errors did not correlate with severity of OCD or depressive symptoms. This study confirms inhibitory deficits, as indicated by increased antisaccade error rates, as a candidate endophenotype of OCD. In agreement with previous findings from imaging studies, our data suggest that functional abnormalities in frontostriatal and parietal cortical regions form part of the vulnerability for OCD.

The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response.

Recently, the neuropeptide S (NPS) neurotransmitter system has been identified as a promising psychopharmacological drug target given that NPS has shown anxiolytic-like and stress-reducing properties and memory-enhancing effects in rodent models. NPS binds to the G-protein-coupled receptor encoded by the neuropeptide S receptor gene (NPSR1). A functional variant within this gene leads to an amino-acid exchange (rs324981, Asn107Ile) resulting in a gain-of-function in the Ile107 variant which was recently associated with panic disorder in two independent studies. A potential psychopharmacological effect of NPS on schizophrenia psychopathology was demonstrated by showing that NPS can block NMDA antagonist-induced deficits in prepulse inhibition. We therefore explored a potential role of the NPSR1 Asn107Ile variation in schizophrenia. A case-control sample of 778 schizophrenia patients and 713 healthy control subjects was successfully genotyped for NPSR1 Asn107Ile. Verbal declarative memory and acoustic startle response were measured in subsamples of the schizophrenia patients. The case-control comparison revealed that the low-functioning NPSR1 Asn107 variant was significantly associated with schizophrenia (OR 1.19, p=0.017). Moreover, specifically decreased verbal memory consolidation was found in homozygous Asn107 carriers while memory acquisition was unaffected by NPSR1 genotype. The schizophrenia patients carrying the Ile107 variant demonstrated significantly reduced startle amplitudes but unaffected prepulse inhibition and habituation. The present study confirms findings from rodent models demonstrating an effect of NPS on memory consolidation and startle response in schizophrenia patients. Based on these findings, we consider NPS as a promising target for antipsychotic drug development.

A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis.

Mutations in postsynaptic scaffolding genes contribute to autism, thus suggesting a role in pathological processes in neurodevelopment. Recently, two de novo mutations in SHANK3 were described in schizophrenia patients. In most cases, abnormal SHANK3 genotype was also accompanied by cognitive disruptions. The present study queries whether common SHANK variants may also contribute to neuropsychological dysfunctions in schizophrenia. We genotyped five common coding or promoter variants located in SHANK1, SHANK2 and SHANK3. A comprehensive test battery was used to assess neuropsychological functions in 199 schizophrenia patients and 206 healthy control subjects. In addition, an independent sample of 77 subjects at risk for psychosis was analyzed for replication of significant findings. We found the T allele of the SHANK1 promoter variant rs3810280 to lead to significantly impaired auditory working memory as assessed with digit span (12.5 ± 3.6 vs. 14.8 ± 4.1, P < .001) in schizophrenia cases, applying strict Bonferroni correction for multiple testing. This finding was replicated for forward digit span in the at-risk sample (7.1 ± 2.0 vs. 8.3 ± 2.0, P = .044). Previously, altered memory functions and reduced dendritic spines and postsynaptic density of excitatory synapses were reported in SHANK1 knock-out mice. Moreover, the atypical neuroleptic clozapine was found to increase SHANK1 density in rats. Our findings suggest a role of SHANK1 in working memory deficits in schizophrenia, which may arise from neurodevelopmental changes to prefrontal cortical areas.

Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early--and additional memory dysfunction in the late--prodromal state.

Impairments in neuropsychological functioning have been described in subjects clinically at high risk for psychosis, but the specific cognitive deficits in different clinical high-risk groups remain to be elucidated. The German Research Network on Schizophrenia employs a heuristic 2-stage model: a putatively late prodromal state (LPS), characterized by the onset of attenuated positive or brief psychotic symptoms, and an early prodromal state (EPS), mainly characterized by the presence of basic symptoms, which are predictive for psychosis within the next 10 years. A total of 205 subjects met the criteria for either an EPS or an LPS of psychosis and were assessed with a comprehensive neuropsychological test battery. Neurocognitive profiles of high-risk groups were compared with data of 87 healthy controls comparable with regard to gender, age, and premorbid verbal IQ. Patients in the LPS were impaired in all neurocognitive domains (memory/learning, executive control/processing speed, and working memory) examined, with memory being the worst. Deficits were less pronounced in patients in the EPS, with a specific deficit in the executive control/processing speed domain. Consistent with a progressive neurodevelopmental disorder, some cognitive abilities were already impaired in patients in the EPS, followed by further deterioration in the LPS. Specifically, deficits in executive control functioning were related to the presence of basic symptoms, indicating a vulnerability for psychosis. Memory deficits were associated with the onset of psychotic symptoms indicating further disease progression in the trajectory to psychosis and, thus, may be useful in predicting psychosis and targeting early intervention.

Neurocognitive indicators of clinical high-risk states for psychosis: a critical review of the evidence.

The present review investigates the empirical evidence from cross-sectional and long-term follow-up studies on neurocognitive indicators of an increased risk for developing schizophrenia spectrum psychoses in clinically defined high-risk samples. First, the investigations at the Cologne center for early recognition and intervention are briefly summarized and then integrated within the available literature. Thirty-two studies with original data could be identified by extensive literature search. Cross-sectional investigations of neurocognitive baseline assessments in high-risk samples with unknown conversion status have produced rather inconsistent results. Nevertheless, most convincing evidence could be collected for abnormal functioning in processing speed measures (digit symbol coding, Trailmaking Test-B, Stroop Color Naming), the Continuous Performance Test, verbal working memory measures, verbal memory and learning, and verbal fluency, though negative findings have also been reported in every instance. Moreover, high-risk subjects were found to perform both at the schizophrenia performance level and at a close to normal level. Longitudinal follow-up assessments provided predictive evidence with regard to psychosis conversion for measures of processing speed and of verbal memory and learning. However, a substantial number of negative findings does not allow for straight-forward conclusions. Finally, some reasons for inconsistent findings are discussed critically speculating on demographic differences, reliability and sample sizes, and conceptual imprecision in communicating results.

A coding variant of the novel serotonin receptor subunit 5-HT3E influences sustained attention in schizophrenia patients.

Sustained attention as measured by the Continuous Performance Test (CPT) has proved a valuable endophenotype for schizophrenia. Recently pharmacological studies suggested a role of the serotonin (5-HT) 3 receptor in schizophrenia. The 5-HT3 receptors are the only ligand-gated ion channels within the 5-HT receptor family. Applying an endophenotype approach, we investigated a potential impact of the genes of the 5-HT3A and 5-HT3B subunits as well as the novel 5-HT3C, 5-HT3D, and 5-HT3E subunits on CPT performance in subjects with schizophrenia. The study included 196 patients with schizophrenia, 113 of their parents, and 205 healthy controls recruited from community registers. Sustained attention was assessed with the Continuous Performance Test-Identical Pairs (CPT-IP). Assessing functional and coding variants of the 5-HT3 receptor subunit genes, we found the GG genotype of the 5-HT3E subunit gene (rs7627615; Thr86Ala) to be associated with better attentional capacities in subjects with schizophrenia and healthy controls. This study provides additional evidence for a role of the serotonergic system and the 5-HT3 receptor in schizophrenia.

Randomized comparison of group cognitive behaviour therapy and group psychoeducation in acute patients with schizophrenia: effects on subjective quality of life.

OBJECTIVE: Although the clinical efficacy of cognitive behaviour therapy (CBT) has been established for patients with schizophrenia, the data on effects on quality of life (QoL) are lacking. The purpose of the present study was therefore to compare the effects of a brief group CBT and a group psychoeducational (PE) programme in patients with schizophrenia on QoL. METHOD: A total of 88 inpatients with schizophrenia were randomized to receive a therapy envelope of 8 weeks including either 16 sessions of group CBT or eight sessions of group PE treatment. QoL was assessed using the Modular System for Quality of Life at baseline, post-treatment assessment and 6 month follow up. RESULTS: QoL improved significantly in both treatments in most QoL dimensions. Within-group effect sizes for general QoL at follow up were 0.25 for CBT and 0.29 for PE. No significant differences between CBT and PE were found at post-treatment and at 6 month follow up. CONCLUSIONS: Both brief group CBT and group PE improve subjective QoL in patients with schizophrenia.

Clinical validity of the "Dimensional Assessment of Personality Pathology (DAPP)" for psychiatric patients with and without a personality disorder diagnosis.

There is a movement towards a dimensional classification of personality disorders (PD). However, data linking dimensional systems and the categorical system for classifying PD are lacking. In the present study, N = 165 normal subjects and N = 222 nonpsychotic in-patients (including N = 81 patients with a PD diagnosis) completed the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ) measuring 18 PD traits. DSM-IV PD symptoms were assessed by SCID-II interviews. Group differences were analyzed by ANCOVA, and the relation between the dimensional and categorical approach was investigated by regression, ROC, and MDS analyses. Patients with PD exhibited elevated scores on all DAPP traits compared with controls. Patients without PD scored in between. Each DSM-IV PD could be described by a distinct profile of DAPP traits. Results support the assumption that the DAPP trait system can represent mean differences between clinically defined subgroups. The categorical system can be mapped onto the dimensional DAPP system with sufficient clinical specificity.

Early onset of obsessive-compulsive disorder and associated comorbidity.

BACKGROUND: Previous studies have aimed to identify subtypes of obsessive-compulsive disorder (OCD) based on their age of onset (AOO). Obsessive-compulsive spectrum disorders (OCS disorders) such as tic disorders have been particularly associated with an early onset in some studies. However, subtypes of early- and late-onset OCD are unevenly determined, and the biological and the clinical validity of these subtypes are unknown. This study was undertaken to discriminate the subtypes of OCD in different AOO levels and to test the hypothesis that different AOO bands are associated with a differential pattern of comorbidity. METHODS: Two hundred fifty-two patients with OCD were interviewed directly with the German version of the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety Version, which provides DSM-IV diagnosis. Subgroups with different ages of onset were investigated (cut-off levels of 10, 15, and 18 years). RESULTS: Subjects with an early AOO (onset < or =10 years) were significantly more likely to have OCS disorders (odds ratio [OR]=3.46; P=.001; 95% confidence interval [CI]: 1.72-6.96), in particular tic/Tourette's disorders (OR=4.63; P=.002; 95% CI: 1.78-12.05), than were late-onset subjects. CONCLUSIONS: For most mental disorders (e.g., anxiety and mood disorders), no associations with AOO of OCD were identified. However, subjects in the early-onset group (< or =10 years) had a significant increase in comorbid tic and Tourette's disorders. Future research should examine potential neurobiological features associated with early-onset presentations of OCD. Early detection and management of comorbidities may offset impairments later in life.

Factor structure of the Hare Psychopathy Checklist: youth version in German female and male detainees and community adolescents.

Substantial evidence exists for 3- and 4-factor models of psychopathy underlying patterns of covariation among the items of the Psychopathy Checklist-Revised (PCL-R) in diverse adult samples. Although initial studies conducted with the Psychopathy Checklist: Youth Version (PCL:YV) indicated reasonable fit for these models in incarcerated male adolescents in the United States and the United Kingdom, only one published study has addressed the factor structure of PCL:YV psychopathy in female adolescents, and no prior studies have addressed it outside of these countries. We used confirmatory factor analysis to investigate the factor structure underlying PCL:YV scores in 314 incarcerated (143 male, 171 female) and 193 in-school (99 male, 94 female) adolescents, ages 14 to 19 years. The 2-factor model provided adequate fit only for incarcerated male adolescents and the 4-factor model was problematic in all samples, but the 3-factor solution provided an adequate model in incarcerated and community male adolescents. None of the models provided consistently acceptable fit among female adolescents. Current findings provide evidence for the robustness of the 3-factor model of psychopathy in incarcerated and community male adolescent samples but raise doubts about the applicability of this model to female adolescents. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

[Toward DSM-V: new approaches for the classification of personality disorders]. / Auf dem Weg zum DSM-V: Neue Ansätze zur Klassifikation von Persönlichkeitsstörungen.

Dissatisfaction with the existing categorical classification system for personality disorders has stimulated DSM-V Research Planning Work Groups to check alternative dimensional representations. Four different strategies have been suggested: 1. dimensional representations of existing categories; 2. dimensional reorganization of diagnostic criteria; 3. integration of personality disorders with dimensional models of general personality structure; 4. identification of spectra of dysfunction cutting across personality, axis I and axis II disorders. Together with models of dimensional classification two further relevant aspects are discussed: First, the question of stability and changeability of personality (disorder) and thus the question of childhood and adolescence antecedents. Second, the search for neuroscientific foundations of personality disorder traits that can be integrated by an endophenotypic approach. These considerations imply a heuristic framework guided by the vision of an etiologically based classification system for personality disorders (and possibly other psychiatric syndromes).

[The impact of emotional stimuli on working memory in female delinquent juveniles]. / Der Einfluss emotionaler Stimuli auf die Arbeitsgedächtnisleistung bei weiblichen delinquenten Jugendlichen.

OBJECTIVE: This paper focuses on the objective to what extent detained girls exhibit deficits with respect to spatial working memory. Moreover, this study investigates the influence of visual emotional stimuli on the working memory of antisocial female juveniles as well as the relationship between the number of errors in performing the different working memory tasks and psychopathy. METHODS: A group of incarcerated female adolescents (n = 33) was compared with a group of non-delinquent students attending grades 10 and 11 of an integrated comprehensive school (n = 20). Three variants of the Subject-Ordered Pointing Task (SOPT: neutral, erotic-, fear-related) and the Psychopathy-Checklist Youth Version (PCL:YV) were administered to the two groups. RESULTS: Analyses of variance showed significant differences between the two groups regarding the neutral and the fear-related variants of the SOPT, but none regarding the erotic-related variant. Hypothesized associations between psychopathy and the neutral variant were affirmed, but not for the fear-related variant of the SOPT. CONCLUSIONS: This study demonstrated similar deficits with respect to neutral working memory in detained female juveniles as have been affirmed for male antisocials within the literature. On the one hand, the expected levelling of the group difference regarding working memory accomplishment in the erotic variant could be explained by an improvement of the often sexually traumatized delinquent female adolescents, and on the other hand by impairment in the control group. The results with respect to working memory accomplishment on the basis of fear-related stimuli indicated that girls with high psychopathy scores differ from antisocial boys and might still react susceptible to emotional stimuli.

Sensory gating in schizophrenia: P50 and N100 gating in antipsychotic-free subjects at risk, first-episode, and chronic patients.

BACKGROUND: Abnormal sensory gating in schizophrenia has frequently been reported; however, only limited data on unmedicated patients and patients at risk to develop a psychosis have, as yet, been available. METHODS: P50 and N100 suppression were assessed with an auditory double-click paradigm in five groups: 18 at-risk subjects who did not develop a full psychosis within the follow-up period of 2 years, 21 truly prodromal subjects who developed frank psychosis within the follow-up period, 46 antipsychotic-naïve subjects with first-episode schizophrenia, 20 antipsychotic-free subjects with chronic schizophrenia, and 46 healthy control subjects. RESULTS: P50 and N100 suppression indices differed significantly between groups and were lowest in chronic schizophrenia patients. Compared with healthy control subjects, P50 suppression was significantly impaired in at-risk subjects, truly prodromal and first-episode patients (stimulus 2 [S2]/stimulus 1 [S1] P50 amplitude ratio), and chronic schizophrenia patients (difference and ratio), and N100 suppression was significantly reduced in truly prodromal and first-episode patients (S1-S2 difference) and in chronic schizophrenia patients (difference and ratio) but not at-risk subjects. At-risk subjects with and without conversion to psychosis did not significantly differ on any test parameter. CONCLUSIONS: Sensory gating is already impaired in early stages of schizophrenia, though this is most prominent in chronic stages. Future studies will have to clarify the type and impact of variables modifying sensory gating disturbances, such as illness progression and genetic load. Furthermore, the meaning and nature of differences between P50 and N100 suppression need further elucidation.

Obsessive-compulsive disorder and posttraumatic stress disorder.

BACKGROUND: Previous studies suggested an association between exposure to trauma or stressful life events and obsessive-compulsive disorder (OCD). This study investigates the hypothesis that traumatic events and posttraumatic stress disorders (PTSD) precede the onset of OCD. SAMPLING AND METHODS: 210 cases with OCD from university treatment facilities were compared with 133 sex- and age-matched controls from the adult general population. The data were derived from a German family study on OCD (GENOS). Direct interviews were carried out with the German version of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version for Anxiety Disorders (DSM-IV). RESULTS: Severe traumatization occurred in 6.2% of the OCD cases and in 8.3% of the controls. The lifetime prevalence rates of traumatization, PTSD and acute stress disorder were not different between the subjects with OCD and controls (p > 0.05). In 6 cases, acute stress disorder, subclinical or full PTSD preceded the onset of OCD, in 3 cases the trauma-related disorders and OCD occurred within the same year, in 5 other cases, the trauma-related disorders started after the onset of OCD. CONCLUSION: There is no significant association of traumatization or PTSD with OCD compared with controls. Given the low rate of trauma-related disorders occurring before (2.9%) or within (1.5%) the same year as the onset of OCD other factors than severe traumatic events determine the onset of OCD in most of the cases.