Toshiya Teraishi

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (63)156.94 Total impact

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    ABSTRACT: AimThe Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes.Methods Subjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy (FA) and mean diffusivity (MD) value derived from DTI data on a voxel-by-voxel basis among the 2 diagnostic groups and healthy subjects.ResultsThere were significant decreases of FA and increases of MD in patients with MDDs compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD.Conclusion Our results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD.
    Psychiatry and Clinical Neurosciences 11/2014; · 2.04 Impact Factor
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    ABSTRACT: Previous studies have suggested that schizophrenia patients have dysfunctional thermoregulation. The aim of this study was to examine whether brain temperature (BT) in schizophrenia patients differs from that in patients with bipolar disorder and healthy subjects by using magnetic resonance imaging. We also evaluated the possible relationship between BT and cerebral blood flow (CBF). We analyzed the temperature of lateral ventricles as the mean BT using diffusion-weighted imaging (DWI) thermometry, and evaluated the relationships between the BT and the CBF using pseudo-continuous arterial spin labeling (pCASL) among 3 diagnostic groups, 22 male patients with schizophrenia, 19 male patients with bipolar disorder, and 23 healthy male subjects. There were significant positive correlations between BT in the lateral ventricles and CBF in both the patients with bipolar disorder and healthy subjects. By contrast, there were significant negative correlations in patients with schizophrenia. We could not detect the significant difference in the surrogates of BT among three diagnostic groups. We showed that patients with schizophrenia, but not those with bipolar disorder, have dysfunctional thermoregulation in the brain. Brain temperature is highly dependent on cerebral metabolism and CBF, and thus uncoupling of cerebral metabolism and CBF may occur in schizophrenics.Journal of Cerebral Blood Flow & Metabolism advance online publication, 3 September 2014; doi:10.1038/jcbfm.2014.151.
    09/2014;
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    ABSTRACT: Tryptophan, an essential amino acid, is the precursor to serotonin and is metabolized mainly by the kynurenine pathway. Both serotonin and kynurenine have been implicated in the pathophysiology of major depressive disorder (MDD). However, plasma tryptophan concentration in patients with MDD has not unequivocally been reported to be decreased, which prompted us to perform a meta-analysis on previous studies and our own data.
    The Journal of clinical psychiatry. 09/2014; 75(9):e906-e915.
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    ABSTRACT: Synthetic glucocorticoids such as dexamethasone are widely used to treat a variety of inflammatory and autoimmune conditions, but they may induce adverse events including hyperglycemia. To shed light on the effect and action mechanism of dexamethasone, we examined the alterations of gene expression levels caused by dexamethasone.Microarray analysis was performed on whole blood collected from 24 physically healthy subjects at baseline and after dexamethasone administration. The expression levels of resistin mRNA were found to be significantly increased after the dexamethasone administration. In a separate sample of 12 subjects, we examined plasma resistin protein levels and found that they were increased after dexamethasone administration. Furthermore, the plasma mRNA and protein levels of resistin were significantly higher in individuals who carried the A allele of RETN single nucleotide polymorphism rs3219175 than in those who did not carry the allele. There was no significant interaction between the genotype and dexamethasone administration. No significant correlation was found between plasma levels of cortisol and resistin. Consistent with previous studies, the genotype of RETN rs3219175 was a strong determinant of resistin levels. The present study showed that oral administration of dexamethasone increases the protein and mRNA levels of resistin irrespective of the rs3219175 genotype.
    07/2014;
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    ABSTRACT: AimPrevious studies consistently reported increased harm avoidance (HA) assessed with the Temperament and Character Inventory (TCI) in patients with major depressive disorder (MDD). However, such findings may have been related with depression severity and number of depressive episodes. The aims of the present study were two-fold: to examine TCI personality profile in remitted MDD (DSM-IV) patients and to compare TCI personality between MDD patients with single episode (SGL-MDD) and those with recurrent episodes (REC-MDD) in order to elucidate personality profile associated with recurrence.MethodsTCI was administered to 86 outpatients with remitted SGL-MDD (12 male and 17 female patients; mean age 43.2 ± 12.1 years) and REC-MDD (26 male and 31 female patients; 40.3 ± 11.6 years), and 529 healthy controls (225 males and 304 females; 43.4 ± 15.5 years), matched for age, sex and education years. Logistic regression analyses were performed, in which single/recurrent episodes of depression was the dependent variable and age, sex, age of onset, family history of psychiatric disease and TCI scores were entered as possible predictors.ResultsThe remitted MDD patients had significantly higher scores on HA (p<0.001) and lower scores on self-directedness (p<0.001), compared with the controls. HA (p=0.03) and its subscore, fatigability (p=0.03) as well as family history of psychiatric disease were found to be positive predictors for recurrence.Conclusion There are differences in personality profile between remitted MDD patients and controls, and between remitted REC-MDD and SGL-MDD patients, suggesting that they are trait markers. HA and fatigability might be useful to assess risk for recurrence of depression.
    Psychiatry and Clinical Neurosciences 07/2014; · 2.04 Impact Factor
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    ABSTRACT: While research on remission in schizophrenia has gained attention, personality characteristics associated with remission in schizophrenia have been under-studied. A functional valine-to-methionine (Val158Met) polymorphism in the catechol-O-methyltransferase (COMT) gene is shown to modify clinical presentation of schizophrenia despite weak or no association with the disorder itself. Studies also report that this polymorphism can affect personality traits. We aimed to examine personality traits of remitted patients with schizophrenia as compared to symptomatic patients and healthy controls and to investigate whether the COMT Val158Met polymorphism influences their personality. Scores on the Temperament and Character Inventory were compared between 34 remitted outpatients with schizophrenia, age- and sex-matched 72 symptomatic outpatients with schizophrenia, and matched 247 healthy individuals. The effect of COMT Val158Met polymorphism on personality was examined in each group. The analysis of covariance, controlling for confounding variables, revealed that compared to healthy controls, symptomatic patients exhibited a pervasively altered personality profile whereas remitted patients showed alterations in more limited personality dimensions and demonstrated normal levels of novelty-seeking, reward dependence and cooperativeness. The two-way analysis of covariance, with genotype and sex as between-subject factors and confounders as covariates, revealed that Met carriers demonstrated significantly lower reward dependence and cooperativeness than Val homozygotes in symptomatic patients; while no significant genotype effect was found in remitted patients or in healthy individuals. These findings indicate that remitted patients with schizophrenia have a relatively adaptive personality profile compared to symptomatic patients. The COMT Val158Met polymorphism might have a modulating effect on the relationship between personality and remission.
    Journal of psychiatric research. 05/2014;
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    ABSTRACT: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a novel noninvasive technique that can measure regional cerebral blood flow (rCBF). To our knowledge, few studies have examined rCBF in patients with schizophrenia by ASL-MRI. Here we used pseudo-continuous ASL (pCASL) to examine the structural and functional imaging data in schizophrenic patients, taking the regional cerebral gray matter volume into account. The subjects were 36 patients with schizophrenia and 42 healthy volunteers who underwent 3-tesla MRI, diffusion tensor imaging (DTI), and pCASL. We evaluated the gray matter volume imaging, DTI, and pCASL imaging data in a voxel-by-voxel statistical analysis. The schizophrenia patients showed reduced rCBF in the left prefrontal and bilateral occipital cortices compared to the healthy volunteers. There was a significant reduction of gray matter volume in the left inferior frontal cortex in the schizophrenia patients. With respect to the fractional anisotropy (FA) values in the DTI, there were significant FA reductions in the left superior temporal, left external capsule, and left inferior prefrontal regions in the patients compared to the controls. Conclusion Our pCASL study with partial volume effect correction together with volumetry and DTI data demonstrated hypoactivity in the left prefrontal area beyond structural abnormalities in schizophrenia patients. There were also hypofunction areas in bilateral occipital cortices, although structural abnormalities were not apparent.
    Schizophrenia Research 04/2014; · 4.59 Impact Factor
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    ABSTRACT: Regulation of hypothalamic-pituitary-adrenal (HPA) axis reactivity plays an important role in the development of stress-related psychiatric disorders. FK506 binding protein 5 (FKBP5) modulates HPA axis reactivity via glucocorticoid receptor (GR; NR3C1) sensitivity and signaling. The T allele of the single nucleotide polymorphism, FKBP5 rs1360780 (C/T), is associated with higher FKBP5 induction by glucocorticoids. In the present study, we performed the dexamethasone/corticotropin releasing hormone (DEX/CRH) test and quantitative real-time PCR analysis of peripheral blood mononuclear cell (PBMC) cDNA samples in 174 and 278 non-clinical individuals, respectively. We found increased suppression of the stress hormone (cortisol) response to the DEX/CRH test (P = 0.0016) in aged (> 50 years) individuals carrying the T allele compared with aged non-T allele carriers. T carriers showed significant age-related changes in GR and FKBP5 mRNA expression levels in PBMCs (P = 0.0013 and P = 0.00048, respectively). Our results indicate that FKBP5 rs1360780 regulates HPA axis reactivity and expression levels of GR and FKBP5 in PBMCs in an age-dependent manner. Because these phenotypes of aged T carriers are similar to endophenotypes of people with post-traumatic stress disorder, our findings may be useful for determining the molecular mechanisms, treatment, and preventive strategies for this disease.
    Psychoneuroendocrinology 01/2014; · 5.59 Impact Factor
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    ABSTRACT: Background Most previous studies that examined regional cerebral blood flow (rCBF) abnormalities in major depressive disorder (MDD) required the injection of radioisotopes into subjects. Here by using magnetic resonance imaging (MRI) with the pseudo-continuous arterial spin labeling (pCASL) method which does not require radioisotopes, we examined rCBF in patients with MDD in comparison with that in patients with schizophrenia and healthy subjects, taking the regional cerebral gray matter volume into account. Methods Subjects were 27 patients with MDD, 42 with schizophrenia and 43 healthy volunteers who underwent 3-T MRI with pCASL. Obtained pCASL imaging data were subject to the voxel-by-voxel statistical analysis. Results There were significant reductions of rCBF in the right inferior prefrontal cortex and anterior cingulate cortices (ACCs) in the MDD patients compared with the healthy controls. When compared with the schizophrenic patients, the MDD patients showed lower rCBF in the subgenual ACC and higher rCBF in left occipital region. Limitation The abnormalities of rCBF in MDD were known to reverse during symptom remission. Further study with follow-up period would bring the perception about the treatment response. Conclusion The rCBF reduction in the subgenual region may be a specific functional abnormality to MDD patients, which may provide a biological marker for MDD. The MRI with pCASL method is a promising tool to detect rCBF abnormalities controlling for gray matter volume in psychiatric disorders.
    Journal of Affective Disorders. 01/2014; 165:59–63.
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    ABSTRACT: Patients with schizophrenia are at increased risk for suicide. Various risk factors for suicide have been reported in schizophrenia; however, few studies have examined the association between personality traits and suicidal behavior. We administered the Schizotypal Personality Questionnaire (SPQ) to 87 Japanese patients with schizophrenia (49 males; mean age 38.1±10.6 years) with and without a history of suicide attempts (SA and nSA groups, respectively), and 322 controls (158 males; mean age 40.8±13.9 years). As expected, an analysis of covariance (ANCOVA) controlling for age and sex showed that all SPQ indices (total SPQ score and all three factors, i.e., cognitive-perceptual, interpersonal, and disorganized) were significantly higher in patients with schizophrenia (SA+nSA groups), than controls (p<0.001 for all comparisons). Furthermore, there were significant differences in the total score and the interpersonal and disorganized factors between the SA and nSA groups (nSA<SA, p<0.01 for all comparisons). Receiver operating characteristic analysis showed that a total SPQ score of 33.5 was the optimal cut-off value to discriminate the SA group from the nSA group (χ2[1] = 10.6, p = 0.002, odds ratio: 4.7, 95% confidence interval: 1.8-12.1, sensitivity: 0.70, specificity: 0.67). These results suggest that high schizotypy is associated with lifetime suicide attempts, and that the total SPQ score might be useful to assess the risk of suicide attempt in patients with schizophrenia.
    PLoS ONE 01/2014; 9(9):e107739. · 3.53 Impact Factor
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    ABSTRACT: FK506 binding protein 5 (FKBP5) is induced by stress and regulates glucocorticoid receptor sensitivity. The T allele of the single nucleotide polymorphism (SNP) FKBP5 rs1360780 (C/T) is associated with an increased risk of post-traumatic stress disorder (PTSD) and reduced hippocampal volume in traumatized or depressed subjects. To examine whether this SNP affects brain structures that regulate stress response, we obtained magnetic resonance imaging data of the brain in 162 healthy subjects using a 1.5 Tesla system. Gray matter volumes and diffusion tensor imaging data were compared between individuals with and without the T allele, using optimized voxel-based morphometry. We found that the dorsal anterior cingulate cortex (dACC) volume was smaller in T carriers than in non-T carriers (P < 0.001). T carriers also showed significantly higher mean diffusivity values in the dACC and posterior cingulate cortex (PCC) compared with non-T carriers (P < 0.001). Our results suggest that carrying the T allele of FKBP5 rs1360780 is associated with smaller gray matter volumes in the dACC and altered white matter integrity in the dACC and PCC in the non-clinical population, which might constitute the structural basis of stress-related psychiatric disorders including PTSD.
    Journal of Psychiatric Research. 01/2014;
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    ABSTRACT: The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 (FKBP5) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD). In the present study, we examined whether this SNP is associated with cognitive function in a non-clinical population. The full versions of the Wechsler Memory Scale-Revised and Wechsler Adult Intelligence Scale-Revised were administered to 742 and 627 Japanese individuals, respectively, followed by genotyping of rs1360780 by the TaqMan 5'-exonuclease allelic discrimination assay. For both cognitive tests, we found significantly poorer attention/concentration (working memory) in aged (>50 years old) individuals carrying the T allele compared with their counterparts. This finding accords with an altered HPA axis and vulnerability to stress-related psychiatric disorders.
    Scientific reports. 01/2014; 4:6696.
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    ABSTRACT: Background Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals. Methods In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains. Results Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals. Limitations The sample size of patients with bipolar disorder was small, and most of the patients were on psychotropic medication. Conclusions These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder.
    Journal of affective disorders 01/2014; 158:90–96. · 3.76 Impact Factor
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    ABSTRACT: l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90 min after an oral intake of l-theanine (0, 200, 400, or 600 mg). PPI tests were done by examiners who were blind to the dose. The administration of 200 mg of l-theanine and that of 400 mg, but not 600 mg, significantly increased the % PPI compared to the baseline (0 mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. The observed effect with 200-400 mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans.
    Psychiatry and Clinical Neurosciences 12/2013; · 2.04 Impact Factor
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    ABSTRACT: A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. The aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. A total of 611 patients with schizophrenia, 868 with MDD, and 1193 healthy controls were successfully genotyped for rs2535629. A significant difference in allele distribution was found between patients with schizophrenia and controls (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.05-1.39, P = 0.0077). A similar trend was found for patients with MDD (OR = 1.11, 95% CI: 0.98-1.26, P = 0.092). The allele distribution in the combined patient group (schizophrenia and MDD) was significantly different from that of the control group (OR = 1.15, 95% CI: 1.03-1.28, P = 0.011). Gene expression microarray analysis of whole blood samples in 39 MDD patients and 40 healthy controls showed that rs2535629 has a strong influence on the expression levels of ITIH4 and GLT8D1. The expression levels of GLT8D1 were significantly higher in patients with MDD than in controls (P = 0.021). To our knowledge, the present study showed for the first time the association of rs2535629 with psychiatric disorders in an Asian population. Our findings suggest that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1.
    Journal of Psychiatric Research 12/2013; · 4.09 Impact Factor
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    ABSTRACT: Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.
    Journal of Psychiatric Research 11/2013; · 4.09 Impact Factor
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    ABSTRACT: Background: Previous studies have suggested that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leads to brain changes. However, few studies have examined the whole brain configuration for an association with HPA axis activity. We examined the relationship between HPA axis activity and the whole brain configuration. Methods: The subjects in this study were 34 healthy female volunteers. HPA axis activity was assessed by the dexamethasone/corticotropin-releasing hormone test. Structural volumes of the brain and diffusion tensor images were obtained, and correlations were evaluated voxel-wise. Results: There was a significantly negative correlation between fractional anisotropy value and cortisol levels at 16:00 h (CL-2) in the anterior cingulum, left parahippocampus and right occipital region. There were significantly positive correlations between mean diffusivity value and CL-2 in the left hippocampus and bilateral parahippocampal regions. Conclusions: Our data suggest that reduced feedback of the HPA axis is associated with reduced neural connectivity throughout the brain, and such an association may be strong in the anterior cingulate, the hippocampus and the parahippocampal regions. © 2013 S. Karger AG, Basel.
    Neuropsychobiology 11/2013; 68(4):205-211. · 2.37 Impact Factor
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    ABSTRACT: Depression is associated with dysfunctional coping styles and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. Studies have shown that maladaptive coping strategies relate to abnormal HPA axis function; however, such a relationship has been under-studied in patients with depression. We aimed to examine whether dysfunctional coping styles in depression would be associated with abnormal cortisol reactivity. Seventy-four outpatients with major depressive disorder and 133 age- and sex-matched healthy individuals were recruited. Coping was assessed by the Ways of Coping Checklist. Psychological distress was assessed by the Hopkins Symptom Checklist. Cortisol reactivity was measured by the combined dexamethasone/corticotropin-releasing hormone test. Compared to healthy individuals, depressed patients demonstrated significantly less use of problem-solving, positive reappraisal and social support coping styles and more use of self-blame and wishful thinking styles. Such a pattern of coping styles was significantly associated with patients' greater distress. Partial correlation analysis in patients, controlling for age and sex, revealed a significant correlation between more use of escape-avoidance coping and lower levels of reactive cortisol measures. A stepwise multiple regression analysis predicting cortisol reactivity from age, sex, distress, symptom severity and coping styles revealed that escape-avoidance coping was a significant predictor. The neuroendocrine challenge test was administered only once, based on a simple test protocol. More use of escape-avoidance coping in depressed patients was associated with less cortisol reactivity. Our findings shed light on the heterogeneity of depression in terms of low and high levels of avoidance associated with exaggerated and blunted HPA axis reactivity, respectively.
    Journal of affective disorders 10/2013; · 3.76 Impact Factor
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    ABSTRACT: Schizotypy is conceptualized as a latent personality construct that confers liability for schizophrenia, while it is also suggested that schizotypy can relate to certain favorable aspects. Investigating individual-level interactions between schizotypy and broader personality characteristics might give a clue to this question. We aimed to identify homogeneous classes of individuals based on schizotypy, temperament and character and to validate this classification using comprehensive neurocognitive data. We studied 455 nonclinical adults using the Schizotypal Personality Questionnaire, the Temperament and Character Inventory, and an array of neuropsychological tests. A latent profile analysis (LPA) of schizotypy, temperament and character was conducted, and cognitive performance was compared as a function of latent class membership. LPA provided a 3-class solution. Of the sample, 15% was classified into a "high-positive-schizotypy/adaptive" group characterized by high cognitive-perceptual but low interpersonal schizotypy, together with low harm avoidance and high self-directedness, cooperativeness and self-transcendence; 18% was classified into a "high-schizotypy/maladaptive" group characterized by overall high schizotypy, together with high harm avoidance and low self-directedness and cooperativeness; and 67% was classified into a "low-schizotypy/adaptive" group characterized by overall low schizotypy, together with intermediate-to-low harm avoidance, high self-directedness and intermediate-to-high cooperativeness. Overall cognitive performance of the high-positive-schizotypy/adaptive group was comparable to that of the low-schizotypy/adaptive group and superior to that of the high-schizotypy/maladaptive group. The present LPA clearly defines a group of individuals who have adaptive personality traits and intact neuropsychological functions despite high positive schizotypy, suggesting that there may be complex, nonlinear relationships between schizotypal traits and psychopathology.
    Journal of Psychiatric Research 10/2013; · 4.09 Impact Factor
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    ABSTRACT: Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population. Subjects were 599 healthy adults (166 males and 433 females; mean age 43.8 +/- 15.5 years). The Wechsler Memory Scale-Revised (WMS-R) was administered to all participants to assess memory performance. Genotyping was performed for 6 selected tagging SNPs of PAH (rs1722387, rs3817446, rs1718301, rs2037639, rs10860936 and rs11111419). Analyses of covariance controlling for sex and education years, indicated a significant association between a SNP (rs2037639) and age-corrected verbal memory index of WMS-R (nominal p = 0.0013) which remained significant after correction for multiple testing ( p = 0.0013 < 0.0017 = 0.05/30tests). Individuals with the GG genotype showed a significantly lower mean verbal memory score, compared with those individuals carrying the AA/AG genotype (106.0 +/- 16.0 vs. 111.7 +/- 13.4; p = 0.00099). A haplotype block containing two markers of rs2037639 and rs10860936 was associated with verbal memory index (permutation global p = 0.0091). Our findings suggest that common genetic variations in PAH are associated with verbal memory in healthy adults. Unknown functional polymorphisms in PAH or those in other genes nearby might affect memory performance.
    Behavioral and Brain Functions 07/2013; 9(1):30. · 2.79 Impact Factor