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Miho Ota,
Noriko Sato,
Junko Matsuo,
Yukiko Kinoshita,
Yumiko Kawamoto,
Hiroaki Hori, Toshiya Teraishi,
Daimei Sasayama,
Kotaro Hattori,
Satoko Obu,
Yasuhiro Nakata,
Hiroshi Kunugi
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ABSTRACT: Prepulse inhibition (PPI) deficits have been reported in individuals with schizophrenia and other psychiatric disorders with dysfunction of the cortico-striato-pallido-thalamic circuit. The purpose of this study was to investigate the structural neural correlates of PPI by using magnetic resonance imaging (MRI) metrics. The subjects were 53 healthy women (mean age; 40.7±11.3 years). We examined the possible relationships between PPI and diffusion tensor imaging (DTI) metrics to estimate white matter integrity and gray matter volume analyzed using the DARTEL (diffeomorphic anatomical registration through exponentiated lie) algebra method. There were significant correlations between DTI metrics and PPI in the parahippocampal region, the anterior limb of the internal capsule, the ventral tegmental area, the thalamus and anterior thalamic radiations, the left prefrontal region, the callosal commissural fiber, and various white matter regions. There were also positive correlations between PPI and gray matter volume in the bilateral parietal gyri and the left inferior prefrontal gyrus at a trend level. The present study revealed evidence of a relationship between PPI and the integrity of white matter. This result was compatible with the previous suggestion that PPI would be modulated by the cortico-striato-thalamic-pallido-pontine circuit.
Brain research 01/2013; · 2.46 Impact Factor
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Daimei Sasayama,
Kotaro Hattori,
Chisato Wakabayashi, Toshiya Teraishi,
Hiroaki Hori,
Miho Ota,
Sumiko Yoshida,
Kunimasa Arima,
Teruhiko Higuchi,
Naoji Amano,
Hiroshi Kunugi
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ABSTRACT: Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded.
Journal of psychiatric research 01/2013; · 3.72 Impact Factor
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Daimei Sasayama,
Hiroaki Hori,
Seiji Nakamura,
Ryo Miyata, Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Noriko Yamamoto,
Teruhiko Higuchi,
Naoji Amano,
Hiroshi Kunugi
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ABSTRACT: Several recent studies have reported that expression quantitative trait loci (eQTLs) may affect gene expression in a cell-dependent manner. In the current study, a genome-wide eQTL analysis was performed in whole blood samples collected from 76 Japanese subjects. RNA microarray analysis was performed for 3 independent sample groups that were genotyped in a genome-wide scan. The correlations between the genotypes of 534,404 autosomal single nucleotide polymorphisms (SNPs) and the expression levels of 30,465 probes were examined for each sample group. The SNP-probe pairs with combined correlation coefficients of all 3 sample groups corresponding to P<3.1×10(-12) (i.e., Bonferroni-corrected P<0.05) were considered significant. SNP-probe pairs with a high likelihood of cross-hybridization and SNP-in-probe effects were excluded to avoid false positive results. We identified 102 cis-acting and 5 trans-acting eQTL regions. The cis-eQTL regions were widely distributed both upstream and downstream of the gene, as well as within the gene. The eQTL SNPs identified were examined for their influence on the expression levels in lymphoblastoid cell lines by using a public database. The results showed that genetic variants affecting expression levels in whole blood may have different effects on gene expression in lymphoblastoid cell lines. Further studies are required to clarify how SNPs function in affecting the expression levels in whole blood as well as in other tissues.
PLoS ONE 01/2013; 8(1):e54967. · 4.09 Impact Factor
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Miho Ota,
Noriko Sato,
Masanori Ishikawa,
Hiroaki Hori,
Daimei Sasayama,
Kotaro Hattori, Toshiya Teraishi,
Satoko Obu,
Yasuhiro Nakata,
Kiyotaka Nemoto,
Yoshiya Moriguchi,
Ryota Hashimoto,
Hiroshi Kunugi
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ABSTRACT: Although schizophrenia and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between the two groups are low. To identify the correlative pattern of brain changes that best discriminate schizophrenia patients from healthy subjects, discriminant analysis techniques using voxel-based morphometry were applied.
The first analysis was conducted to obtain a statistical model that classified 105 female healthy subjects and 38 female schizophrenia patients. First, the differences in gray matter and cerebrospinal fluid volume between the patients and healthy subjects were evaluated using optimized voxel-based morphometry. Then, a discriminant analysis reflecting the results of this evaluation was adopted. The second analysis was performed to prospectively validate the statistical model by successfully classifying a new group that consisted of 23 female healthy subjects and 23 female schizophrenia patients.
The use of these variables resulted in correct classification rates of 0.72 in the control subjects and 0.76 in the schizophrenia patients. In the second validation analysis using these variables, correct classification rates of 0.70 in the control subjects and 0.74 in the schizophrenia patients were achieved.
Schizophrenia patients have structural deviations in multiple brain areas, and a combination of structural brain measures can distinguish between patients and controls.
Psychiatry and Clinical Neurosciences 12/2012; 66(7):611-7. · 2.13 Impact Factor
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ABSTRACT: BACKGROUND: Evidence shows that depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, although such findings are not entirely unequivocal. In contrast, various psychiatric conditions, including atypical depression, are associated with hypocortisolism. Another line of research has demonstrated that personality is associated with HPA axis alteration. It is thus hypothesized that different personality pathology in depression would be associated with distinct cortisol reactivity. METHODS: Eighty-seven outpatients with DSM-IV major depressive disorder were recruited. Personality was assessed by the temperament and character inventory (TCI). HPA axis reactivity was measured by the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. According to our previous studies, two subgroups were considered based on their cortisol responses to the DEX/CRH test: incomplete-suppressors whose cortisol response was exaggerated and enhanced-suppressors whose cortisol response was blunted. RESULTS: The analysis of covariance, controlling for age, gender and symptom severity, revealed that incomplete-suppressors scored significantly higher on cooperativeness than enhanced-suppressors (p=0.002). A multivariate stepwise logistic regression analysis predicting the cortisol suppression pattern from the seven TCI dimensions, controlling for age, gender and symptom severity, revealed that lower cooperativeness (p=0.001) and higher reward dependence (p=0.018) were significant predictors toward enhanced suppression. LIMITATIONS: The neuroendocrine challenge test was administered only once, based on a simple test protocol. CONCLUSIONS: Our findings suggest that (personality-related) subtypes of depression might be differentiated based on the different pattern of cortisol reactivity. Future studies are warranted to further characterize the HPA axis alteration in relation to various subtypes of depression.
Journal of affective disorders 11/2012; · 3.76 Impact Factor
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ABSTRACT: Accumulating evidence indicates that oxytocin plays an important role in social interactions. Previous studies also suggest altered oxytocin function in patients with schizophrenia and depression. However, few studies have examined the central oxytocin levels in these disorders.
Cerebrospinal fluid (CSF) oxytocin levels were measured by ELISA in male participants consisting of 27 patients with schizophrenia, 17 with major depressive disorder (MDD), and 21 healthy controls.
CSF oxytocin levels of patients with schizophrenia or MDD did not differ significantly with healthy controls. The antidepressant dose or the Hamilton depression rating scale score did not significantly correlate with the oxytocin levels in MDD patients. CSF oxytocin levels in schizophrenic patients significantly negatively correlated with second generation antipsychotic dose (r=-0.49, P=0.010) but not with first generation antipsychotic dose (r=-0.13, P=0.50). A significant correlation was observed between oxytocin levels and negative subscale of PANSS (r=-0.38, P=0.050). This correlation remained significant even after controlling for second generation antipsychotic dose (r=-0.47, P=0.016).
We obtained no evidence of altered CSF oxytocin levels in patients with schizophrenia or those with MDD. However, lower oxytocin levels may be related to higher second generation antipsychotic dose and more severe negative symptoms in schizophrenia.
Biological Psychiatry 06/2012; 139(1-3):201-6. · 8.28 Impact Factor
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ABSTRACT: It is generally acknowledged that schizophrenia and schizotypy lie on the same continuum, while there is an ongoing debate as to whether schizotypy represents true dimension or quasi-dimension. Evidence suggests that reduced hemispheric lateralization and mixed handedness are associated with both schizophrenia and schizotypy. However, the possible relationship of schizotypy with laterality as assessed with motor function tasks has not been well documented. A few studies using fine motor control tasks have demonstrated the relationship between schizotypy and reduced laterality among student populations, yet little has been done in community samples. Here we employed 249 healthy women and examined the association between schizotypal traits assessed with the Schizotypal Personality Questionnaire and motor functions assessed with the Purdue Pegboard test (as a measure of spatial motor control) and a handgrip force test. Correlational and categorical analyses both showed that schizotypal traits were significantly associated with leftward and bilateral bias in the fine motor control task, but not in the handgrip force test. Schizotypy did not significantly affect the performance level on either of these tasks. These results indicate that schizotypal traits in healthy women are associated with a shift away from dextrality, supporting the fully dimensional model of schizotypy.
Psychiatry Research 06/2012; · 2.52 Impact Factor
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ABSTRACT: BACKGROUND: Growing evidence suggests that schizotypy and genetic loading for schizophrenia both represent risk for the development of schizophrenia. Although these conditions are known to be associated with neurocognitive impairments, such an association has not been studied in patients with bipolar II disorder (BPII) or unipolar major depressive disorder (UP). METHODS: Forty-one depressed patients with BPII, 131 patients with UP and demographically matched 225 healthy controls were recruited. Schizotypy was assessed by the Schizotypal Personality Questionnaire. Neuropsychological functioning was measured by the Wechsler Memory Scale-Revised, the Wechsler Adult Intelligence Scale-Revised and the Wisconsin Card Sorting Test. RESULTS: Mood disorder patients performed significantly worse than controls in verbal and visual memory, working memory and processing speed. BPII patients performed significantly more poorly than UP patients in verbal memory and executive functioning. Both BPII and UP patients demonstrated significantly greater schizotypal traits than controls. Schizotypy was significantly negatively correlated with verbal comprehension both in BPII and UP patients and with working memory and processing speed in healthy controls. Patients who had one or more first-degree relatives with schizophrenia performed significantly more poorly than the remaining patients in all cognitive domains. LIMITATIONS: Most of our patients were on psychotropic medication, and the sample of BPII patients was not very large. CONCLUSIONS: Liability for schizophrenia could play a pivotal role in neurocognitive functioning in mood disorders, suggesting that such liability might lie on a continuum ranging from normality through mood disorders to full-blown schizophrenia.
Journal of affective disorders 06/2012; · 3.76 Impact Factor
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ABSTRACT: The β3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression.
The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls.
No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027).
We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2012; 38(2):341-4. · 3.25 Impact Factor
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Takashi Fujii,
Miho Ota,
Hiroaki Hori,
Daimei Sasayama,
Kotaro Hattori, Toshiya Teraishi,
Noriko Yamamoto,
Miyako Hashikura,
Masahiko Tatsumi,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Human P-glycoprotein (P-gp), which is encoded by ABCB1 (ATP-binding cassette, sub-family B member 1), is expressed in the blood brain barrier and protects the brain from many kinds of drugs and toxins including glucocorticoids by acting as an efflux pump. We examined whether functional polymorphisms of ABCB1 give susceptibility to major depressive disorder (MDD). The five functional single nucleotide polymorphisms (SNPs), A-41G (rs2188524), T-129C (rs3213619), C1236T (Gly412Gly: rs1128503), G2677A/T (Ala893Ser/Thr: rs2032582), and C3435T (Ile1145Ile: rs1045642) were genotyped in 631 MDD patients and 1100 controls in the Japanese population. A tri-allelic SNP, G2677A/T, was genotyped by pyrosequencing and the remaining SNPs were genotyped by the TaqMan 5'-exonuclease allelic discrimination assay. The minor T3435 allele was significantly increased in MDD patients than in the controls (χ(2) = 4.5, df = 1, p = 0.034, odds ratio [OR] 1.16, 95% confidential interval [CI] 1.01-1.34). Homozygotes for the T3435 allele was significantly more common in patients than in the controls (χ(2) = 7.5, df = 1, p = 0.0062, OR 1.43, 95%CI 1.11-1.85). With respect to the other 4 SNPs, there was no significant difference in genotype or allele distribution. In the haplotype-based analysis, the proportion of individuals with the TT1236-TT3435 haploid genotype was significantly increased in patients than in controls (χ(2) = 8.5, df = 1, p = 0.0037, OR 1.50, 95%CI 1.14-1.98). Our results suggest that the T3435 allele or carrying two copies of this allele confers susceptibility to MDD in the Japanese population.
Journal of psychiatric research 02/2012; 46(4):555-9. · 3.72 Impact Factor
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ABSTRACT: Ca(2+)-dependent activator protein for secretion 2 (CADPS2), a secretory granule associate protein, mediates monoamine transmission and neurotrophin release. Both monoamines and neurotrophins play a crucial role in cognition, learning and memory. An aberrant splice variant of CADPS2, CADPS2ΔExon3, was reported to be associated with autism. Therefore, we examined the possible association between the expression of CADPS2/CADPS2ΔExon3 in peripheral blood and brain functions such as intelligence and memory. Quantitative polymerase chain reaction analysis was performed in 271 healthy adults (age range 20-74 years, mean ± SD 43.3 ± 15.3). Data on intelligence quotient (IQ) and memory were obtained by using full versions of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Wechsler Memory Scale-Revised (WMS-R), respectively. CADPS2 expression levels were not significantly associated with any scores/sub-scores of these scales. However, CADPS2ΔExon3 expression was significantly associated with lower IQ (p=0.022; effect size: η(p)(2)=0.031), particularly verbal IQ of WAIS-R (p=0.019; η(p)(2)=0.032), lower verbal memory (p=0.026; η(p)(2)=0.026) and delayed recall (p=0.042; η(p)(2)=0.021) of WMS-R. Our results suggest that CADPS2ΔExon3 affects intelligence and memory in the non-clinical population.
Biological psychology 01/2012; 89(1):117-22. · 4.36 Impact Factor
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Hiroaki Hori,
Noriko Yamamoto,
Takashi Fujii, Toshiya Teraishi,
Daimei Sasayama,
Junko Matsuo,
Yumiko Kawamoto,
Yukiko Kinoshita,
Miho Ota,
Kotaro Hattori,
Masahiko Tatsumi,
Kunimasa Arima,
Hiroshi Kunugi
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ABSTRACT: Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some evidence suggests that this polymorphism plays a role in cognitive function both in schizophrenia patients and healthy individuals; however, the precise nature of this association remains unclear. Here we investigated the possible association of this polymorphism with a wide range of neurocognitive functions in schizophrenia patients and in healthy subjects. Schizophrenia patients exhibited significantly poorer performance on all the cognitive domains as compared to healthy controls. In patients, A-allele carriers demonstrated significantly worse logical memory performance than the G-allele homozygotes. In controls, no significant association was observed between the genotype and any of the cognitive domains examined. These results add to the literature suggesting that rs1006737 may be associated with schizophrenia through its detrimental effect on endophenotypic traits.
Scientific Reports 01/2012; 2:634.
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Daimei Sasayama,
Hiroaki Hori, Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Junko Matsuo,
Yumiko Kawamoto,
Yukiko Kinoshita,
Miyako Hashikura,
Naoji Amano,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls.
Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender.
Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R+L+B) was significantly lower in both patients with unipolar depression and bipolar disorder (P=0.0034 and P<0.0001, respectively). Furthermore, R+L+B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R+L+B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P=0.0028). Limitations Bipolar patients during manic episode were not included in the study.
Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders.
Journal of affective disorders 12/2011; 136(3):1047-52. · 3.76 Impact Factor
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Takashi Fujii,
Noriko Yamamoto,
Hiroaki Hori,
Kotaro Hattori,
Daimei Sasayama, Toshiya Teraishi,
Miyako Hashikura,
Masahiko Tatsumi,
Nagahisa Okamoto,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Altered neurotrophin functions have been implicated in major depressive disorder (MDD). Previously, we reported an association between MDD and a missense polymorphism (Ser205Leu: rs2072446) of the gene encoding the p75 neurotrophin receptor (p75(NTR)). However, contradictive negative results have also been reported. This study tried to replicate the association in an independent sample. Subjects were 668 patients with MDD and 1130 healthy controls. The proportion of individuals carrying the Leu205 allele was significantly decreased in the patients than in the controls (χ(2)=5.3, d.f.=1, P=0.021, odds ratio (OR) 0.74, 95% confidential interval (CI) 0.58-0.96). When allele frequencies were compared, the Leu205 allele was significantly reduced in the patients than in the controls (χ(2)=4.4, d.f.=1, P=0.037, OR 0.78, 95% CI 0.61-0.99). When men and women were examined separately, there was a significant difference in genotype and allele distributions in women (genotype: χ(2)=8.3, d.f.=1, P=0.0039, OR 0.60, 95% CI 0.43-0.85; allele: χ(2)=7.3, d.f.=1, P=0.0069, OR 0.64, 95% CI 0.47-0.89), but not in men. The present study provided support for the previously reported association between the Ser205Leu polymorphism of the p75(NTR) gene and MDD, indicating that the Leu205 allele has a protective effect against the development of MDD, particularly in women.
Journal of Human Genetics 09/2011; 56(11):806-9. · 2.57 Impact Factor
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ABSTRACT: Wechsler adult intelligence scale-revised was performed in 576 healthy adults to examine whether a functional polymorphism (Asp358Ala) of the IL-6 receptor (IL-6R) gene is associated with cognitive performance. Verbal intelligence quotient in Asp homozygotes was significantly higher compared to Ala carriers (P = 0.005). Compared to Ala carriers, Asp homozygotes performed better in the verbal subtests requiring long-term memory stores. Elevated IL-6 and soluble IL-6R levels in Ala carriers may have negative impact on acquiring verbal cognitive ability requiring long-term memory.
Acta Neurovegetativa 08/2011; 119(3):313-8. · 2.73 Impact Factor
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ABSTRACT: Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1β) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms.
A total of 533 patients with schizophrenia (302 males: mean age ± standard deviation 43.4 ± 13.0 years; 233 females; mean age 44.8 ± 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 ± 17.3 years; 748 females; 46.3 ± 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia.
Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032).
The present study shows the first evidence that the IL-1β gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1β gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1β in the etiology of schizophrenia.
Behavioral and Brain Functions 08/2011; 7:35. · 2.13 Impact Factor
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ABSTRACT: While schizophrenia has been associated with a slight excess of winter/early spring birth, it is unclear whether there is such an association in relation to schizotypal personality traits. Season of birth has also been reported to relate to temperament and character personality dimensions and cognitive functioning. Moreover, non-clinical schizotypy has been shown to be associated with mild cognitive impairment, although its precise nature is yet to be elucidated. Here we examined the relationships between season of birth, schizotypal traits, temperament and character, and cognitive function. Four hundred and fifty-one healthy adults completed the Schizotypal Personality Questionnaire (SPQ). The Temperament and Character Inventory (TCI) and a neuropsychological test battery consisting of full versions of the Wechsler Memory Scale-Revised and the Wechsler Adult Intelligence Scale-Revised, and the Wisconsin Card Sorting Test, were also administered to most of the participants. The total SPQ score of those born in winter was significantly higher than that of the remaining participants. Season of birth was not significantly associated with any of the TCI dimensions or cognitive test results. Significant but mild relationships between higher SPQ scores and lower scores on some aspects of IQ were observed. These results support the notion that schizotypy and schizophrenia are neurodevelopmental conditions on the same continuum.
Psychiatry Research 08/2011; 195(1-2):69-75. · 2.52 Impact Factor
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Daimei Sasayama,
Chisato Wakabayashi,
Hiroaki Hori, Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Masanori Ishikawa,
Kunimasa Arima,
Teruhiko Higuchi,
Naoji Amano,
Hiroshi Kunugi
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ABSTRACT: Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis × genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia.
Journal of psychiatric research 06/2011; 45(11):1439-44. · 3.72 Impact Factor
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Daimei Sasayama,
Hiroaki Hori, Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Junko Matsuo,
Yumiko Kawamoto,
Yukiko Kinoshita,
Teruhiko Higuchi,
Naoji Amano,
Hiroshi Kunugi
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ABSTRACT: Interleukin-1β (IL-1β) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1β gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1β gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (60 years) females without dementia. We selected five tagging polymorphisms from the IL-1β gene and examined the associations with the WAIS-R scores. Significant associations were found between verbal intelligence quotient (IQ) and the genotypes of rs1143634 and rs1143633 (P=0.0037 and P=0.010, respectively). No significant associations of rs16944 genotype were found with verbal or performance IQ. However, individuals homozygous for the G allele of rs16944 achieved higher scores in digit span compared with their counterpart, which is consistent with the previous findings in males. These results suggest that IL-1β gene variation may have a role in cognitive functions in aging females as well as males.
Journal of Human Genetics 05/2011; 56(8):613-6. · 2.57 Impact Factor
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ABSTRACT: Ca(2+)-dependent activator protein for secretion 2 (CADPS2), a secretory granule associate protein, mediates monoamine transmission and the release of neurotrophins including brain-derived neurotrophic factor (BDNF) which have been implicated in psychiatric disorders. Furthermore, the expression of CADPS2deltaExon3, a defective splice variant of CADPS2, has been reported to be associated with autism. Based on these observations, we examined whether expression levels of CADPS2 and CADPS2deltaExon3 are altered in psychiatric disorders. Quantitative polymerase chain reaction analysis was performed for postmortem frontal cortex tissues (BA6) from 15 individuals with schizophrenia, 15 with bipolar disorder, 15 with major depression, and 15 controls (Stanley neuropathology consortium). The mean CADPS2 expression levels normalized to human glyceraldehyde-3phosphate dehydrogenase (GAPDH) or TATA-box binding protein levels was found to be significantly increased in the brains of the schizophrenia group, compared to the control group. On the other hand, the ratio of CADPS2deltaExon3 to total CADPS2 was similar in the 4 diagnostic groups. We then analyzed CADPS2 expression in blood samples from 121 patients with schizophrenia and 318 healthy controls; however, there was no significant difference between the two groups. Chronic risperidone treatment did not alter the expression of CADPS2 in frontal cortex of mice. The observed increase in the expression of CADPS2 may be related to the impaired synaptic function in schizophrenia.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2011; 35(7):1738-43. · 3.25 Impact Factor
