Syudo Yamasaki

1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia.

Schizophrenic and normal control subjects were examined using both 1H-magnetic resonance spectroscopy (MRS) and structural MR imaging, in order to accurately assess the partial volume within the spectroscopic volume of interest (VOI) in the anterior cingulate cortex. The gray matter volume within VOI correlated positively with the N-acetyl-aspartate (NAA) to choline (Cho) ratio in schizophrenics only, not in controls. Schizophrenic patients had a reduced NAA/Cho ratio and an elevated Cho/creatine ratio compared to controls after the partial volume effect was eliminated. There was a significant negative correlation between the NAA/Cho ratio and the severity of blunted affect symptom in schizophrenics. These results provide further support to the idea that the measures of 1H-MRS indicate not only neuronal loss but also neuronal dysfunction in schizophrenia.

Reduced gray matter volume of pars opercularis is associated with impaired social communication in high-functioning autism spectrum disorders.

BACKGROUND Recent literature suggests that the inferior frontal gyrus, especially its posterior portion, has an important role in imitation and social reciprocity and in the pathophysiology of their disturbance in autism spectrum disorders (ASD). However, the structural abnormality of this region has not fully been clarified in subjects with ASD. METHODS Here we obtained magnetic resonance images from 13 right-handed men with high-functioning ASD (Asperger disorder [n = 10] or autism [n = 3]) and from 11 age-, parental socioeconomic background-, and intelligence quotient-matched right-handed typical men. A reliable manual tracing methodology was employed to measure the gray matter volume of the pars opercularis, corresponding to Brodmann area 44, and the pars triangularis, corresponding to Brodmann area 45. RESULTS A significant gray matter volume reduction of both the pars opercularis and triangularis was found bilaterally in the subjects with ASD compared with the typical control subjects. The effect size seemed to be larger for pars opercularis (1.25) than for pars triangularis (.90). The reduced volume of right as well as total pars opercularis showed a significant association with the increased severity of social communication problems in the ASD group. CONCLUSIONS The current findings support an important role of pars opercularis, a center of the mirror neuron system, in the pathophysiology of ASD.

A multimodal approach to investigate biomarkers for psychosis in a clinical setting: The integrative neuroimaging studies in schizophrenia targeting for early intervention and prevention (IN-STEP) project

Longitudinal clinical investigations and biological measurements have determined not only progressive brain volumetric and functional changes especially around the onset of psychosis but also the abnormality of developmental pathways based on gene-environment interaction model. However, these studies have contributed little to clinical decisions on their diagnosis and therapeutic choices because of subtle differences between patients and healthy controls. A multi-modal approach may resolve this limitation and is favorable to explore the pathophysiology of psychosis. The integrative neuroimaging studies for schizophrenia targeting early intervention and prevention (IN-STEP) is a research project aimed at exploring the pathophysiological features of the onset of psychosis and investigating possible predictive biomarkers for the clinical treatment of psychosis. Since 2008, we have adopted blood sampling, neurocognitive batteries, neurophysiological assessment, structural imaging, and functional imaging longitudinally for help-seeking ultra-high-risk (UHR) individuals and patients with first-episode psychosis (FEP). Here, we intend to introduce the IN-STEP research study protocol and present preliminary clinical findings. Thirty-seven UHR individuals and 30 patients with FEP participated in this study. Six months later, there was no difference in objective and subjective scores between the groups, which suggests that young people having symptoms and functional deficits should be cared for regardless of their history of psychosis according to their clinical stages. The rate of transition to psychosis was 7.1%, 8.0%, and 35.3% (at 6, 12, and 24months, respectively). Through this research project, we expect to clarify the pathophysiological features around the onset of psychosis and improve the prognosis of psychosis through clinical application.

Reduced planum temporale volume and delusional behaviour in patients with schizophrenia

The structural abnormality of planum temporale (PT), a part of the superior temporal heteromodal association cortex involved in auditory and language processing, has been implicated in the pathophysiology of schizophrenia. However, its relationship to clinical manifestations remains unclear. Magnetic resonance images were obtained from 17 right-handed Japanese men with schizophrenia and from 22 age-, handedness-, and parental socioeconomic-status-matched healthy Japanese men in order to manually evaluate grey matter volumes of Heschl’s gyrus (HG) and PT. Psychiatric symptoms were assessed using positive and negative syndrome scale among the patients. Compared with healthy participants, patients with schizophrenia were associated with a statistically significant PT grey matter volume reduction without left or right lateralization, whereas HG volume was preserved. Smaller right PT volume was significantly correlated with more severe delusional behaviour in the patients. Previous investigations have focused on smaller-than-normal left PT in the pathophysiology of schizophrenia; however, the present results suggest a possible role of the right PT, which is involved in social cognition such as understanding the intentions of others, in the production of psychotic experiences in patients with schizophrenia.

Reduced gray matter volume of Brodmann’s Area 45 is associated with severe psychotic symptoms in patients with schizophrenia

Previous literature has suggested an important role of inferior frontal gyrus, which mainly consists of Brodmann’s Area (BA) 44 and 45, in the pathophysiology of schizophrenia. While recent neuroimaging techniques have revealed differential functional correlates of BA 44 and 45 in healthy individuals, previous studies have not yet separately evaluated the gray matter volume reduction of BA 44 and 45 and their relationships to psychotic symptoms in patients with schizophrenia. In the present study, magnetic resonance images were obtained from 29 right-handed male patients with schizophrenia and from 29 age- and handedness-matched healthy male controls. The reliable manual tracing methodology was employed to measure the gray matter volume of BA 44 and BA 45. The severities of psychotic symptoms were evaluated using the five-factor model of positive and negative syndrome scale in the patient group. A significant gray matter volume reduction of both the BA 44 and BA 45 was found bilaterally in the patients with schizophrenia compared with the healthy controls. Among these inferior frontal sub-regions, reduced volume of right BA 45 revealed the largest effect size. In addition, the reduced volume of BA 45 in left hemisphere showed a significant association with the increased severity of delusional behavior, while the severity of disorganized and positive symptoms were correlated with the bilateral BA 45 volumes in the patient group. The findings support an important role of inferior frontal gyrus in the pathophysiology of schizophrenia. The present study further demonstrated that BA 45 might especially contribute to the production of psychotic symptoms in the patients with schizophrenia.

A greater number of somatic pain sites is associated with poor mental health in adolescents: a cross-sectional study

BackgroundIdentifying indicators of poor mental health during adolescence is a significant public health issue. Previous studies which suggested an association between the number of somatic pains and depression have mainly focused on adults or have employed samples with a narrow age range. To date, results from previous studies have been inconsistent regarding the association between somatic pain and academic impairment. Therefore, the main aims of the present study were to 1) investigate the association between the number of somatic pain sites and poor mental health using a community sample of adolescents aged 12 to 18 years and employing a simple method of assessment, and 2) examine the association between the number of somatic pain sites and perceived academic impairment.MethodsData analysis was conducted using a large cross-sectional survey of adolescents in grades 7 to 12. The one-month prevalence rates for three sites of somatic pain including head, neck and shoulders, and abdomen were examined. Poor mental health was evaluated using the General Health Questionnaire, and perceived academic impairment was measured using a self-report questionnaire.ResultsA total of 18,104 adolescents participated in the survey. A greater number of pain sites was associated with poor mental health, and this association was consistent across age and gender. There was no difference in effect on mental health between any of the pain sites. Although there was an association between the number of somatic pain sites and perceived academic impairment, the results suggested that the association was mediated by poor mental health.ConclusionsSimple reporting methods for assessing the number of pain sites may be a feasible indicator of poor mental health in adolescents. Professionals working with adolescents should consider the possibility of poor mental health, especially when students report multiple somatic pains.

Risk for suicidal problems in poor-help-seeking adolescents with psychotic-like experiences: findings from a cross-sectional survey of 16,131 adolescents

BACKGROUND Recent evidence suggests that psychotic-like experiences (PLEs) in the general population are important markers of risk of suicidal problems. However, there have been no epidemiological studies investigating help-seeking status in individuals with PLEs and elevated risk of suicide. METHODS Information on PLEs, self-awareness of mental distress (SAMD), help-seeking behaviours (HSBs), and suicidal problems was collected from 16,131 Japanese adolescents. Participants were divided into two groups, those with and without PLEs, and then both groups were further divided into three subgroups: a group without SAMD, who had no HSB by definition; a group with both SAMD and HSB; and a group with SAMD but without HSB (poor-help-seeking group), yielding a total of six groups. RESULTS Adolescents with PLEs (14.3%) had significantly higher risk of suicidal problems than those without PLEs. Among the individuals with both PLEs and SAMD, 38.1% did not seek any help (poor-help-seeking status). Among the six groups, odds of suicidal ideation was the highest among poor-help-seeking adolescents with PLEs, with a 20-fold increase compared to those without PLEs, SAMD and HSB (adjusted for age and sex), while the odds was increased 10-fold in those with PLEs, SAMD and HSB. After adjusting for anxiety/depression level, the odds ratios remained significant in both poor-help-seeking adolescents with PLEs (OR=3.8 [3.0-4.9 (95% CI)]) and those with PLEs, SAMD and HSB (OR=2.5 [2.0-3.1]). CONCLUSIONS Adolescents with PLEs and self-awareness of mental distress are at high risk for suicidal problems, particularly those without help seeking.

Neurophysiological impairment in emotional face processing is associated with low extraversion in schizophrenia

Patients with schizophrenia have low extraversion and high neuroticism. These personality traits affect the everyday life of patients with schizophrenia, making it important to investigate neurobiological basis of personality traits. In healthy people, extraversion is associated with hemodynamic responses in the amygdala and electrophysiological brain activity such as event-related potential and event-related desynchronization during emotional face processing. Patients with schizophrenia show abnormal neural activity during emotional face processing, such as an N170 amplitude reduction. However, few studies to date have reported an association between personality traits and neural activity during emotional face processing in schizophrenia. In the present study, we examined N170 during emotional face processing, and association with personality traits in patients with schizophrenia. Fifteen male patients with chronic schizophrenia and 15 healthy male subjects participated in this study. Patients with schizophrenia had reduced N170 amplitudes (p=0.007). While healthy subjects had increased N170 amplitudes in response to emotional faces compared with neutral faces (p=0.003), patients with schizophrenia showed no difference in N170 amplitudes between emotional and neutral faces (p=0.60). Reduced N170 amplitude in response to neutral faces was correlated with low extraversion scores in patients with schizophrenia (r(s)=-0.69, p=0.005). The abnormal N170 and its association with extraversion in schizophrenia were found at the right rather than the left posterior temporal electrode. An abnormal N170 in schizophrenia may reflect impairments in the structural encoding of emotional faces, and indiscrimination between emotional and neutral faces at this stage of information processing. The association between abnormal N170 amplitudes and extraversion suggests that abnormal neural activity in the early stages of emotional face processing may underlie low extraversion characteristic of schizophrenia.

New instrument for measuring multiple domains of social cognition: Construct validity of the Social Cognition Screening Questionnaire (Japanese version)

The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ) (Japanese version).

Genetic influences on prefrontal activation during a verbal fluency task in adults: a twin study based on multichannel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) studies have reported that prefrontal hemodynamic dysfunction during executive function tasks may be a promising biomarker of psychiatric disorders, because its portability and noninvasiveness allow easy measurements in clinical settings. Here, we investigated the degree to which prefrontal NIRS signals are genetically determined. Using a 52-channel NIRS system, we monitored the oxy-hemoglobin (oxy-Hb) signal changes in 38 adult pairs of right-handed monozygotic (MZ) twins and 13 pairs of same-sex right-handed dizygotic (DZ) twins during a letter version of the verbal fluency task. Heritability was estimated based on a classical twin paradigm using structured equation modeling. Significant genetic influences were estimated in the right dorsolateral prefrontal cortex and left frontal pole. The degrees of heritability were 66% and 75% in the variances, respectively. This implies that the prefrontal hemodynamic dysfunction observed during an executive function task measured by NIRS may be an efficient endophenotype for large-scale imaging genetic studies in psychiatric disorders.