[The International Study of Burnout Syndrome among Psychiatric Trainees (BoSS International) : Findings from Statistical Analysis of the Japanese Data (BoSS Japan)].

BACKGROUND: Burnout is a psychological condition that may occur after being exposed to excessive and prolonged work-related stresses. Previous studies have demonstrated that the rate of burnout among physicians may be higher compared to other occupations ; and espe- cially psychiatric trainees would have a higher risk of burnout because of limited clinical expe- rience, the burden of heavy duties and longer work-hours etc. In this study, we report the findings from Japanese data obtained as part of the international study of burnout syndrome among psychiatric trainees (BoSS International). METHODS: This study was initiated by members of the European Federation of Psychiatric Trainees (EFPT) and the European Psychiatric Association-European Early Career Psychia- trists (EPA-EECP). The total number of participating nations was 22 countries. A national coordinator recruited study collaborators all over Japan and psychiatric trainees working at their medical institutes were invited to participate in BoSS International by e-mail. The sub- jects were requested to answer the on-line questionnaire anonymously. Consent was obtained when making a list of potential participants at each institute and reconfirmed on the first page of the on-line questionnaire. Answering the questionnaire was deemed to constitute consent. RESULTS: Total number of participants to BoSS International was 7,525 from 22 countries and regions. Of them, 1,980 psychiatric trainees fully completed answering the questionnaire (response rate (RR) 26.0%) including 95 Japanese trainees (RR 41.5%). The mean age of 95 Japanese psychiatric trainees (male rate 67.4%) enrolled in BoSS International was 31.8?4.8 year-old. Their mean clinical experience was 2.9 ?4.4 years. The mean weekly working hours were 72.3?27.1, which was the longest of the 22 participating countries/regions ; while weekly clinical supervision by a mentor was only 3.8?9.0 hours. Regarding the severity of burnout, assessed by using the Maslach Burnout Inventory-General Survey (MBI-GS) consisting of three factors (emotional exhaustion, cynicism, and low sense of professional efficacy): 41 Japanese psychiatric trainees (42.0%) meet the criteria of severe burnout syndrome in this study ; with emotional exhaustion scores of 2.20 and higher, and cynicism of 2.00 and higher. Signifi- cant differences were found on the PHQ-9 score and mean length of supervision between those participants with presence and absence of severe burnout syndrome by using Student's t-test. CONCLUSION: Statistical analyses of the whole data (n=1,980) revealed that the risk of burnout was higher for trainees who were younger, without children, and had not opted for psychiatry as a first career choice. Further analyses after adjustment for socio-demographic characteristics and country difference still demonstrated severe burnout was associated with long working hours, less supervision, and not having regular rest. The analyses of Japanese data showed similar tendencies, although statistical significance was not observed. Burnout among psychiatry trainees may be linked to drop-out from the training program and malprac- tice in clinical settings. We should be aware of the higher risk of burnout in residents and the importance of regular and sufficient supervision to prevent burnout.

HTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in Schizophrenia.

Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy at week 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted.

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients.

BACKGROUND: Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japanese schizophrenia. METHODS: Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. RESULTS: Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). CONCLUSION: Our results show that HTR7 variants are not related to the overall improvement in schizophrenia symptoms.

Antagonist and partial agonist at the dopamine D2 receptors in drug-naïve and non-drug-naïve schizophrenia: a randomized, controlled trial.

Few data are available on the efficacy and safety of antipsychotics with different dopamine D2 receptor (D2-R)-binding properties in drug-naïve and non-drug-naïve schizophrenia. Thus, we aimed to assess whether antipsychotic medication history influences efficacy and tolerability in schizophrenia, based on a randomized controlled study of antipsychotics with mechanisms involving either full antagonism or partial agonism of D2-R. Patients with schizophrenia were recruited and given perospirone or aripiprazole in a 12-week, flexible-dose, open-label, randomized controlled study. Data were analyzed after dividing the patients into antipsychotic-naïve and antipsychotic-treated group according to antipsychotic medication histories. Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Drug-Induced Extrapyramidal Symptoms Scale, and the Barnes Akathisia Rating Scale. In patients receiving perospirone, the antipsychotic-naïve group (n = 22) showed greater symptom improvement than that shown by the antipsychotic-treated group (n = 29), as assessed by efficacy evaluation scales such as the PANSS total, positive, and excited component score (p = .006, p < .001, p = .003, respectively). In patients receiving aripiprazole, however, there was no significant difference in efficacy between the antipsychotic-naïve (n = 18) and antipsychotic-treated (n = 31) groups. No significant intra-group or inter-group difference was noted with respect to any of the tolerability-related parameters assessed. The present study data support the hypothesis that antipsychotic medication history may influence efficacy in patients who receive a D2-R full antagonist but not a D2-R partial agonist.

Grey and white matter proportional relationships in the cerebellar vermis altered in schizophrenia.

Magnetic resonance imaging studies frequently report abnormalities of the cerebellar vermis in schizophrenia, though with some discrepancies as to the nature and location of such abnormalities. Imaging studies typically investigate volumetric differences between groups. Yet substantial evidence supports the hypothesis that grey and white matter proportions in the mammalian brain are controlled by scaling relationships. If strong proportional relationships between grey and white matter tissue volumes are observed in the healthy vermis, then disturbances to these proportions might characterize vermian dysmorphology in schizophrenia. Measures of grey and white matter tissue volumes from three anatomical divisions of the vermis were obtained from 52 patients with chronic schizophrenia and 55 healthy controls. Cross-correlations of the tissue class volumes were computed for each subject group, controlling for age. The number of significant correlations in each group were compared. In addition, the grey/white matter ratio was computed within and across each vermian division. Differences in mean and variance were assessed using t and F tests. A false discovery rate of 0.05 controlled for multiple comparisons. Among controls, 11 of 15 correlations were significant. Among patients, eight of 15 correlations were significant. Five of the nine grey/white matter ratios had an increased mean in the patient group, and all of the variances were trend level or significantly increased in the patients. Tissue class volumes in the cerebellar vermis were strongly interrelated in controls. These relationships were disturbed in patients with schizophrenia.

5-HT2A gene variants influence specific and different aspects of antidepressant response in Japanese and Italian mood disorder patients.

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants.

Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study.

AIM: Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia. Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors. There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies. To clarify the clinical traits of perospirone in the treatment of schizophrenia, the clinical efficacies and side-effects of perospirone and risperidone were compared in a randomized clinical multicenter trial. METHODS: Sixty-six schizophrenia patients were enrolled in the trial. The Positive and Negative Syndrome Scale (PANSS) total, positive, negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) scores were investigated at 0, 4, 8 and 12 weeks. RESULTS: Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups, with no significant between-group differences at 4 and 12 weeks. Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8. There were no significant differences in the DIEPSS scores at 0, 4, 8 and 12 weeks between the perospirone and risperidone groups. The numbers of patients who dropped out did not differ between the perospirone and risperidone groups. CONCLUSIONS: Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia. Both antipsychotic agents were equally well-tolerated.

[5-HT1A gene polymorphisms contributed to antidepressant response in major depression].

Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found to affect the expression and function of HTR1A. In fact rs6295C/G is in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than or together with the synonymous rs6295C/G. In the present study we examined the possible association of a panel of markers in strong linkage disequilibrium of HTR1A with SSRI/SNRI response in 137 Japanese major depression subjects followed for 6 weeks. We observed a significant association of better response to antidepressant in rs10042486C/C (P < 0.0001), rs6295G/G (P < 0.0001) and rs1364043T/T (P = 0.018) genotype carriers, independently from clinical variables. Furthermore minor allele homozygous carriers in all these 3 SNPs were associated with treatment response by various assessments such as HAM-D score change over time (P = 0.001), week 2 (P < 0.0001), 4 (P = 0.007), and 6 (P = 0.048) as well as response rate (P = 0.0005) and remission rate (P = 0.004). We also pointed out the genotyping mis-definition of rs6295C/G in the previous four papers.

Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder.

Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found to affect the expression and function of HTR1A. In fact rs6295C/G is in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than or together with the synonymous rs6295C/G. In the present study we examined the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression subjects followed for 6 weeks. We observed a significant association of better response to antidepressant in rs10042486C/C (P < 0.0001), rs6295G/G (P < 0.0001) and rs1364043T/T (P = 0.018) genotype carriers (minor allele homozygotes), independently from clinical variables. Furthermore minor allele homozygous carriers in all these three SNPs were associated with treatment response by various assessment such as HAM-D score change over time (P = 0.001), week 2 (P < 0.0001), 4 (P = 0.007), and 6 (P = 0.048) as well as response rate (P = 0.0005) and remission rate (P = 0.004). We also pointed out the genotyping mis-definition of rs6295C/G in the previous four articles. In conclusion, this is the first study that reports a significant association of antidepressant response with rs10042486C/T and rs1364043T/G variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.

Corpus callosum in patients with obsessive-compulsive disorder: diffusion-tensor imaging study.

PURPOSE: To prospectively examine microstructural white matter abnormalities in the corpus callosum (CC) of patients with obsessive-compulsive disorder (OCD), as compared with control subjects, and to investigate the relationship between diffusion-tensor (DT) imaging measures of the CC region and clinical symptoms of OCD. MATERIALS AND METHODS: Institutional review board approval was obtained, and each participant--or the participant's parent(s)--provided written informed consent. Sixteen patients with OCD (seven male, nine female; mean age, 28.7 years +/- 9.8 [standard deviation]) and 16 matched healthy volunteers (control subjects) (seven male, nine female; mean age, 29.9 years +/- 9.0) were examined. Mean diffusivity and fractional anisotropy (FA) were measured in five subdivisions of the CC. The paired t test was performed to compare the mean diffusivity or the FA in CC regions between the patients with OCD and the control subjects. RESULTS: There were no significant differences (rostrum, P = .15; genu, P = .88; rostral body, P = .12; isthmus, P = .77; splenium, P = .88) in mean diffusivity between the patients with OCD and the healthy volunteers. A significant reduction in FA was observed in the rostrum of the CC in patients with OCD compared with the rostral FA in the control subjects (P < .001). Higher FA in only the rostrum correlated significantly with lower Yale-Brown obsessive-compulsive scale score (r = -0.72, P = .002). CONCLUSION: Study results support the widely held view that the orbital prefrontal region is involved in the pathophysiology of OCD and indicate that the orbitofrontal circuit influences symptom severity in patients with OCD.

The alpha 2A-adrenergic receptor gene polymorphism modifies antidepressant responses to milnacipran.

OBJECTIVE: The alpha 2A-adrenergic receptor (ADRA2A) plays a central role in the regulation of systemic sympathetic activity. Recently, the functional defect of ADRA2A has been implicated as a cause of depression, attention deficit hyperactivity disorder, and Tourette syndrome. In this study, the effect of genetic variants of the ADRA2A gene on the response to selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) was examined in depressed patients. METHOD: Ninety-three Japanese depressed patients were recruited in the present study, assigned randomly to paroxetine or milnacipran, and assessed by the Hamilton Rating Scale for Depression (HAM-D) scoring every 2 weeks before and after drug administration. The ADRA2A C-1297G polymorphism was considered in the association analysis with the efficacy of antidepressants. RESULTS: There were significant differences in the HAM-D percent score change over time (P = 0.019) among C/C, C/G, and G/G of the ADRA2A C-1297G polymorphism in the total subjects. The C allele carriers of the ADRA2A C-1297G polymorphism showed a significantly better improvement than G/G subjects at weeks 2, 4, and over time (P = 0.037) in the milnacipran group. DISCUSSION: Our findings suggest that ADRA2A plays an important role in depression therapy. The level of ADRA2A expression could be associated with the efficacy of SSRIs/SNRIs, especially milnacipran, although the functional change brought about by C-1297G polymorphism has not yet been fully identified in vivo and in vitro. CONCLUSIONS: The ADRA2A polymorphism could be a reasonable candidate to predict the response to milnacipran. Our results are still preliminary, and a large sample size will be required to confirm our findings. However, to the best of our knowledge, this study is the first to suggest a possible association of ADRA2A variants with the SNRI response.

Antidepressant response and intolerance to SSRI is not influenced by G-protein beta3 subunit gene C825T polymorphism in Japanese major depressive patients.

The G-protein beta3 subunit (GNB3) gene is a key modulator of signal transduction and is a major candidate for SSRIs response. The aim of the present study is to test a possible effect of the C825T polymorphism on the antidepressant response and intolerance to selective serotonin reuptake inhibitors (SSRIs) in 146 Japanese samples with major depression treated with paroxetine or fluvoxamine for 6 weeks. The severity of depression symptom was assessed using the 21-item Hamilton Rating Scale for Depression (HAM-D) and adverse drug reactions were evaluated bi-weekly. No association with SSRIs treatment response was observed in 107 completers also including HAM-D baseline scores, SSRI type or/and 5-HTTLPR variants in the model as covariates. Furthermore, no significant association could be observed with intolerance to SSRIs in the whole subjects. The result suggests that C825T variants of GNB3 cannot play a major role as a predictor of treatment response as well as intolerance to SSRIs in Japanese patients with major depression.

ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder.

Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Multidrug resistance 1 (ABCB1, MDR1) gene encodes a blood-brain barrier transporter P-glycoprotein that plays an important role in controlling the passage of substances between the blood and brain. In the present study, we therefore examined the possible association of 3 functional ABCB1 polymorphisms (C3435T: rs1045642, G2677T/A: rs2032582 and C1236T: rs1128503) with response to paroxetine in a Japanese major depression sample followed for 6 weeks. Analysis of covariance at week 6 with baseline scores included in the model as covariate showed significant association of the non-synonymous SNP G2677T/A with treatment response to paroxetine (p=0.011). Furthermore, the wild variants haplotype (3435C-2677G-1236T) resulted associated with poor response (p=0.006). To our best knowledge, this study is the first suggestion of a possible association of ABCB1 variants with SSRIs response.

Suicidal ideation and burnout among psychiatric trainees in Japan.

AIM: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International. METHODS: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory-General Survey (MBI-GS). RESULTS: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively. CONCLUSIONS: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents.

A pharmaco-EEG study on antipsychotic drugs in healthy volunteers.

RATIONALE: Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle). OBJECTIVES: We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle. METHODS: Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands. RESULTS: Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1. CONCLUSIONS: The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.

Cerebellar posterior superior vermis and cognitive cluster scores in drug-naive patients with first-episode schizophrenia.

Previously, we performed an MRI study that revealed smaller volumes of the subregions of the cerebellar vermis in men and women with chronic schizophrenia. An issue that arose from that study was whether similar structural changes in the cerebellum are found in patients with first-episode schizophrenia. In the present study, MRI scans were acquired from 14 drug-naive patients with first-episode schizophrenia and 16 healthy subjects, and used to measure the volumes of their cerebellar subregions. Positive symptom, negative symptom and cognitive cluster scores were attained using the Positive and Negative Syndrome Scale. Patients with first-episode schizophrenia had reduced volumes of the anterior vermis and posterior superior vermis compared with healthy subjects. We confirmed that there was a volume reduction of the cerebellar vermis in drug-naive patients with first-episode schizophrenia. Smaller volumes of the posterior superior vermis were associated with worse cognitive cluster scores in patients with first-episode schizophrenia.

No association of TPH1 218A/C polymorphism with treatment response and intolerance to SSRIs in Japanese patients with major depression.

BACKGROUND: Variability in antidepressant response is due to genetic and environmental factors. Since SSRIs exert their activity enhancing the serotonin turnover, genes coding for proteins of the serotonin system are key candidates for a possible genetic influence with response to SSRIs. Therefore tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin in the raphe nuclei could be a candidate. In the present study, we examined the possible association of the TPH1 218A/C polymorphism with response to SSRIs in a sample of Japanese patients with major depression. METHODS: The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the TPH1 218A/C polymorphism. RESULTS: Repeated-measures analysis of variance of HAM-D score change over time with baseline scores and 5-HTTLPR variants included in the model as covariate showed no significant association of this SNP with treatment response to SSRIs. Furthermore, no significant association of this SNP could be observed with both responder rate at weeks 2, 4 and 6 and intolerance to SSRIs. CONCLUSION: The result suggests that 218A/C variants of TPH1 cannot play a major role as predictor of treatment response as well as intolerance in Japanese patients with major depression.

Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: A diffusion tensor imaging study.

Disconnection in the frontal-thalamic-cerebellar circuit is thought to be associated with cognitive abnormality in patients with schizophrenia. The superior cerebellar peduncle is involved in neural connectivity in the circuit. Because diffusion tensor imaging (DTI) can detect neural disconnection, we investigated whether there was neural disruption in the superior cerebellar peduncle in patients with schizophrenia. DTI was performed in 21 schizophrenic subjects and 21 age- and sex-matched healthy subjects. Cognitive cluster scores were attained by using the Positive and Negative Syndrome Scale (PANSS). Schizophrenic subjects had significantly lower fractional anisotropy (FA) in the right and left superior cerebellar peduncles than healthy subjects. Higher FA in the left superior cerebellar peduncle was associated with worse cognitive function in patients with schizophrenia. These findings suggest that there is neural disruption in the superior cerebellar peduncle in patients with schizophrenia, which may be involved in the cognitive abnormalities found in schizophrenia.

Altered white matter/gray matter proportions in the striatum of patients with schizophrenia: a volumetric MRI study.

OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.

Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism.

The present study aimed to compare the effects of two currently used selective serotonin reuptake inhibitors (SSRIs) in Japan taking the individual background in 5-HTT gene-linked polymorphic region (5HTTLPR) genotype into account. Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression. Patients with the l allele had a greater percentage reduction on the total score (P=0.059) and somatic anxiety items (P=0.026) of the 21-item Hamilton Depression Rating Scale (HAM-D) score compared to s/s genotype carriers. Paroxetine was significantly more effective than fluvoxamine in the s/s carriers, as evaluated on the percentage reduction in total score (P=0.012) and core (P=0.049) HAM-D after 4 weeks of medication, but not in the l/s carriers. These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs, and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis.