Failure to confirm an association between the PLXNA2 gene and schizophrenia in a Japanese population

Plexins are receptors for multiple classes of semaphorins, either alone or in combination with neuropilins. Plexins participate in many cellular events that include axonal repulsion, axonal attraction, cell migration, axon pruning, and synaptic plasticity. PLXNA2 maps to chromosome 1q32. Several linkage studies reported schizophrenia susceptibility loci in the 1q22-42 region. A recent study reported that intronic single nucleotide polymorphisms (SNPs) of PLXNA2 were associated with schizophrenia in a European American population. We attempted to replicate this finding in a Japanese sample of 336 patients with schizophrenia and 304 controls. In addition, we examined 3 non-synonymous SNPs (Arg5Gln, GLn57Arg, and Ala267Thr) in PLXNA2. Genotyping was performed by the TaqMan allelic discrimination assay. There was no significant difference in genotype or allele distribution of either the 4 intronic SNPs or the 3 non-synonymous SNPs between patients and controls. Furthermore, haplotype-based analyses did not provide evidence for an association. These results suggest that PLXNA2 may not play a major role in the development of schizophrenia in our Japanese sample.     

Gender-specific associations of depression with positive and negative symptoms in acute schizophrenia

This clinical study analyzed gender-specific relationships of depression with other psychopathological and clinical variables in hospitalized patients with schizophrenia. During clinical routine treatment 119 inpatients with acute schizophrenia (DSM-IV) were investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS), the Clinical Global Impressions (CGI), and the Positive and Negative Syndrome Scale (PANSS). Depression scores of 77 male and 42 female patients (mean age 31.6+/-10.3 years) were related to background variables and to positive and negative symptom scores. Mean CDSS (5.8+/-5.6) and PANSS scores (total 76.9+/-22.1, positive symptoms 17.6+/-7.6, negative symptoms 20.5+/-7.8) were not significantly different between males and females. In females, depression was independently associated with higher negative symptom scores (P<0.01) and younger age (P<0.05) whereas in males positive symptoms (P<0.05) and short hospitalization (P<0.05) were the main factors associated with depression. The study revealed gender-specific differences in the relationship of depression with negative and positive symptoms.     

Réformer la nosographie psychiatrique par la mathématisation. Progrès scientifique et nécessité sociale du DSM-III

The DSM-III introduced a new approach of the psychiatric diagnosis by statistics, relying on the quantification of the diagnostic reliability. It thus proceeded to significant changes in the diagnostic categories. These changes were also defined by another principle called “atheorism”. This reform was undertaken by North-American psychiatry as it was crossing a form of crisis, during which the knowledge, the know-how, the autonomy and the ethic of the psychiatrists were questioned. This article intends to emphasize the social and scientific issues at stake in this use of statistics to define mental disorders. We therefore put the DSM-III in the perspective of the empiricism in psychiatry and present the way it was received and the effects it had. We venture in conclusion the hypothesis that DSM-III was a response to the question of the existence of North-American psychiatry as a profession and we try to apply this hypothesis to current French psychiatry.     

The relationship between symptom severity and regional cortical and grey matter volumes in schizophrenia

Objective

To investigate the relationship between symptom severity and cortical and grey matter volumes in schizophrenia.

Method

Fifty-three outpatients with schizophrenia were assessed by the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. Symptoms were grouped into five factors (negative, relational, inattention, disorganization, and reality distortion). Cortical and lobar grey matter volumes within all regions of the brain were obtained from magnetic resonance images using two independent software tools. The relationships between brain volumes and symptom factors were analyzed by partial correlations controlling for age, gender, dose and type of antipsychotic medication, and intracranial volume.

Results

Negative symptoms were generally associated with larger cortical volumes in all regions of the brain, and the relational and inattention factors were associated with larger frontal grey matter volumes. The reality distortion factor was associated with smaller cortical volumes throughout the brain and with smaller frontal and temporal grey matter volumes.

Conclusion

Differential contribution of positive and negative symptoms to variation in cortical and grey matter volumes indicates separate neurobiological mechanisms underlying the two major symptom domains in schizophrenia.     

One-year prevalence and incidence of depression among first-year university students in Japan: a preliminary study

A structured interview was used to examine the 1-year incidence and prevalence of depression among 116 first-year university students. While 24 of the subjects (20.7%) met the Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV) criteria for Major Depressive Episode (MDE), 62 (53.4%) met the Diagnostic and Statistical Manual of Mental Disorders 3rd ed. Revised (DSM-III-R) criteria for MDE, and 27 (23.3%) also met the Research Diagnostic Criteria (RDC) for Major Depressive Disorder (MDD) for the 12 months prior to the interview. Moreover, 23 of the subjects (19.8%) had onset of the DSM-IV criteria for MDE, 54 (46.6%) had onset of the DSM-III-R criteria for MDE, 24 (20.7%) had onset of the RDC for MDD, during the same time period. These high rates of depression may be explained by the students' difficulties in and by their readjustment after entering university.     

Major depressive disorder skews the recognition of emotional prosody

Objective

Major depressive disorder (MDD) is associated with abnormalities in the recognition of emotional stimuli. MDD patients ascribe more negative emotion but also less positive emotion to facial expressions, suggesting blunted responsiveness to positive emotional stimuli. To ascertain whether these emotional biases are modality-specific, we examined the effects of MDD on the recognition of emotions from voices using a paradigm designed to capture subtle effects of biases.

Methods

Twenty-one MDD patients and 21 healthy controls (HC) underwent clinical and neuropsychological assessments, followed by a paradigm featuring pseudowords spoken by actors in five types of emotional prosody, rated on continuous scales.

Results

Overall, MDD patients performed more poorly than HC, displaying significantly impaired recognition of fear, happiness and sadness. Compared with HC, they rated fear significantly more highly when listening to anger stimuli. They also displayed a bias toward surprise, rating it far higher when they heard sad or fearful utterances. Furthermore, for happiness stimuli, MDD patients gave higher ratings for negative emotions (fear and sadness). A multiple regression model on recognition of emotional prosody in MDD patients showed that the best fit was achieved using the executive functioning (categorical fluency, number of errors in the MCST, and TMT B-A) and the total score of the Montgomery-Asberg Depression Rating Scale.

Conclusions

Impaired recognition of emotions would appear not to be specific to the visual modality but to be present also when emotions are expressed vocally, this impairment being related to depression severity and dysexecutive syndrome. MDD seems to skew the recognition of emotional prosody toward negative emotional stimuli and the blunting of positive emotion appears not to be restricted to the visual modality.     

Efficacy of aqueous extract of Echium amoenum in treatment of obsessive–compulsive disorder

Traditionally, the dried flower of Echium amoenum (Boraginaceae) has been used in Iran as an anxiolytic and mood enhancer. This study investigated the efficacy and safety of an aqueous extract of E. amoenum in treatment of obsessive–compulsive disorder. Forty-four patients were randomly assigned to receive either E. amoenum aqueous extract (500 mg/day) or placebo in a 6-week, double blind, parallel-group trial. Patients were assessed before the study and during weeks 1, 2, 4, and 6 by the Yale-Brown Obsessive Compulsive (Y-BOCS), the Hamilton Rating Scale for Anxiety (HAM-A), and a score sheet on adverse effects. In weeks 4 and 6, the extract showed a significant superiority over placebo in reducing obsessive and compulsive and anxiety symptoms. There was no significant difference between the two groups in terms of adverse effects. The results suggest that E. amoenum aqueous extract has some anti obsessive and compulsive effects. However, further studies are needed to confirm these findings.     

Effects of haloperidol on cognition in schizophrenia patients depend on baseline performance: a saccadic eye movement study

Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients.     

Possible association between the -2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain

Antipsychotic-induced weight gain has important effects on treatment compliance and long-term health. Several reports have indicated that a -2548A/G single-nucleotide polymorphism (SNP) of the leptin gene is associated with antipsychotic-induced weight gain. We hypothesized that there is a similar relationship between the -2548A/G SNP and olanzapine-induced weight gain. A total of 74 Korean schizophrenic patients were examined. Their weight was measured before starting olanzapine and after long-term treatment lasting for at least 3 months. The weight gain was significantly higher for patients with the AG genotype than for those with the AA genotype (p=0.029). Analysis of covariance also showed the difference of weight gain was still significant when adjusted for sex and treatment duration (p=0.046). This finding supports the presence of a relationship between the -2548A/G SNP of the leptin gene and weight gain in Korean schizophrenic patients receiving olanzapine treatment.     

The Classification of Anxiety and Fear-Related Disorders in the ICD-11

Anxiety disorders are highly prevalent worldwide and engender substantial economic costs and disability. The World Health Organization is currently developing the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11), which represents the first opportunity to improve the validity, clinical utility, and global applicability of the classification in more than 25 years. This article describes changes in the organization and diagnostic guidelines for anxiety and fear-related disorders proposed by the ICD-11 Working Group on the Classification of Mood and Anxiety Disorders and the rationale and evidence base for the proposals. In ICD-11, anxiety and fear-related disorders that manifest across the lifespan are brought together under a new grouping, and are partly distinguished by their focus of apprehension. The focus of apprehension is the stimulus or situation that triggers the fear or anxiety and may be highly specific as in specific phobia or relate to a broader class of situations as in social anxiety disorder. The guidelines also clarify the relationship between panic disorder and agoraphobia and a qualifier is provided for panic attacks in the context of other disorders. A standardized format emphasizing essential features of anxiety disorders is intended to improve clinical utility. Guidelines will be further refined based on findings from two types of field studies: those using a case-controlled vignette methodology disseminated via the Internet to practitioners worldwide ( http://gcp.network ) and clinic-based field trials implemented globally at participating field study centers.     

High plasma nesfatin-1 level in patients with major depressive disorder

Aim

In the present study, our aim was to determine the changes in the plasma concentrations of a recently discovered peptide hormone nesfatin-1 in patients with major depressive disorder and then to make a comparison with the control group.

Method

Subjects in the patient group were randomly selected from Mustafa Kemal University, Medical School, Research and Training Hospital, Psychiatry Department, Outpatient Clinic and subjects in the control group were selected from healthy volunteers. Healthy control subjects were matched in terms of weight and body mass index. Hamilton Depression Rating Scale (HAM-D) was applied to both groups. ELISA method was used for measurement of plasma nesfatin-1 levels.

Results

The average nesfatin-1 level was statistically higher in patients with major depressive disorder than in the control group (p < 0.001). A positive correlation was observed between plasma nesfatin-1 levels and HAM-D scores both in the patient group (r = 0.59, p < 0.001) and in the control group (r = 0.58, p < 0.001).

Conclusion

Our findings suggest a possible relationship between major depressive disorder and high plasma nesfatin-1 level.     

Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals

Previously, we have shown that orally administered topiramate, a sulfamate-substituted fructopyranose derivative, appears to accentuate rather than diminish some aspects of methamphetamine-induced positive subjective mood and cognitive performance. One possible mechanism by which this might occur would be for topiramate to increase plasma methamphetamine level. Such an effect also would be expected to enhance methamphetamine-induced hemodynamic response. We, therefore, studied -- in the same experiment from which the previous findings originated -- the effects of topiramate on the kinetic profile and hemodynamic response to methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent individuals participated in a double-blind, placebo-controlled, cross-over design, with oral doses of topiramate (0, 100, and 200 mg) administered as a pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The 3x3 factorial combination of topiramate and methamphetamine resulted in a sequence of the nine treatments administered to each subject in an order determined by a 9x9 Latin Square design. Methamphetamine alone was associated with prototypical increases in hemodynamic response that were not altered in the presence of topiramate. While there was no significant kinetic interaction between topiramate and methamphetamine, there was a non-significant trend for topiramate to increase plasma methamphetamine level. No significant adverse events were reported. The combination of topiramate and methamphetamine at pharmacologically relevant doses appears to be safe. Larger laboratory studies with chronic dosing regimens are needed to establish whether or not there is a kinetic interaction between topiramate and methamphetamine.     

PTSD in children and adolescents: toward an empirically based algorithma

In considering potential revisions for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐V), describing developmental influences on symptomatic expression is a high priority. This review presents a number of options and preliminary recommendations to be considered for DSM‐V. Research conducted in the past 15 years is reviewed that pertains to expressions of posttraumatic stress disorder (PTSD) symptoms in preschool and school age children and in adolescents. This research has attempted to determine the usefulness of the DSM‐IV criteria for PTSD in children and adolescents. Based on the studies of preschool children, evidence supports two sets of suggestions: first, we suggest that developmental manifestations are warranted in A‐D criteria of PTSD; and second, we suggest that a developmental preschool PTSD subtype is warranted that lowers the C threshold from three to one symptom. For school‐age children and young adolescents, the evidence is more limited. Nevertheless, there is also evidence suggesting that modifications in PTSD criteria A–D, including fewer Cluster C symptoms, may facilitate accurate diagnosis in this age group. Depression and Anxiety, 2011.© 2010 Wiley‐Liss, Inc.     

Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: A pilot study

We recorded event-related potentials (ERPs) in patients with schizophrenia before and after treatment with quetiapine, to investigate this drug's effects on cognitive function. Auditory and visual oddball stimulus discrimination paradigms were presented to patients with schizophrenia (N = 20) before and after 3 months' treatment with quetiapine. The 2-stimulus auditory oddball paradigm used a standard tone (1000 Hz, 75 dB, 80%) and a target tone (2000 Hz, 75 dB, 20%). The 2-stimulus visual oddball paradigm used a standard stimulus (small circle, 80%) and a target stimulus (large circle, 20%). Patients' severity of psychopathology was initially evaluated with the Positive and Negative Syndrome Scale (PANSS) and was likewise re-evaluated after treatment. After treatment with quetiapine, patients' P300 amplitudes increased over baseline for both tasks (auditory stimuli, P < 0.01; visual stimuli, P < 0.01) and their P300 latencies for both target stimuli decreased significantly (auditory stimuli, P < 0.001; visual stimuli, P < 0.01). Visual P300 amplitude was negatively correlated with the severity of positive symptoms at the Fz electrode before the treatment (r = − 0.45, P < 0.05). After treatment with quetiapine, there were no significant correlations between severity of positive or negative symptoms and visual P300 amplitudes for midline electrodes. These findings suggest that the reduced and delayed P300 may be a state marker for schizophrenia, which may in turn be modulated by positive symptoms, and also suggest that the amplitude and latency for both auditory and visual tasks may be decreased by quetiapine treatment. Based on these results, we suggest that the atypical antipsychotic quetiapine may improve some aspects of cognitive domains in patients with schizophrenia.     

Zonisamide produces weight loss in psychotropic drug-treated psychiatric outpatients

This study examined the long-term effectiveness and tolerability of zonisamide for weight control in psychiatric outpatients using various psychotropic medications. We conducted a systematic chart review of 82 psychiatric outpatients with unwanted weight gain after the introduction of psychotropic drugs between January 2008 and September 2009 at Korea University Ansan Hospital. The primary outcome measure was the effect of zonisamide on body mass index (BMI). Additional outcome measures included safety and tolerability as assessed by the clinical global impression-severity of illness scale (CGI-S) and discontinuation rate. The mean final dose of zonisamide was 124.6 ± 53.4 mg/day and ranged from 50 mg/day to 300 mg/day. The mean BMI reduction was 0.8 ± 1.7 kg/m² and ranged from − 2.9 kg/m² to 4.7 kg/m² (p < 0.001). We also observed a significant reduction in CGI-S scores from the baseline (3.8 ± 0.9) to the endpoint (3.3 ± 0.8; p < 0.001). Twelve patients (14.6%) discontinued their zonisamide treatment due to its side effects. Patients treated with zonisamide showed significant weight loss. Furthermore, its treatment was generally safe and well tolerated with few negative effects on patients' overall psychiatric symptoms. Additional research is required to confirm these results and to investigate whether patients have rebound weight gains after discontinuing zonisamide.