Atsushi Furuichi

Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: A voxel-based diffusion tensor imaging study

Although not consistently replicated, diffusion tensor imaging (DTI) studies in schizophrenia have revealed lower fractional anisotropy (FA) in various white matter regions, a finding consistent with the disruption of white matter integrity. In this study, we used voxel-based DTI to investigate possible whole-brain differences in the white matter FA values between 58 schizophrenia patients and 58 healthy controls. We also explored the association between FA values and clinical symptoms in schizophrenia. Compared with the controls, the schizophrenia patients showed significant FA reductions in bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, and genu of right internal capsule. Furthermore, in the patient group, the FA value of the anterior part of the corpus callosum was negatively correlated with the avolition score on the Scale for the Assessment of Negative Symptoms. These findings suggest widespread disruption of white matter integrity in schizophrenia, which could partly explain the severity of negative symptomatology.

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (-1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval=2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, -2.6%/year; right, -2.3%/year) compared with schizotypal patients (left: -0.4%/year; right: -0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.

Altered depth of the olfactory sulcus in first-episode schizophrenia

A shallow olfactory sulcus has been reported in chronic schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this abnormality exists at the early illness stage and/or develops progressively over the course of the illness. This magnetic resonance imaging (MRI) study investigated the length and depth of the olfactory sulcus in 64 first-episode schizophrenia patients and 64 controls, of whom longitudinal MRI data (mean inter-scan interval=2.6 years) were available for 20 patients and 21 controls. In the cross-sectional comparison at the baseline, the schizophrenia patients had a significantly shallower olfactory sulcus compared with the controls bilaterally, but there was no group difference in its anterior-posterior length. A longitudinal comparison demonstrated that the sulcus length and depth did not change over time in either group. The olfactory sulcus measures of the patients did not significantly correlate with clinical variables such as onset age, medication or symptom severity. These findings suggest that the olfactory sulcus depth, but not length, may be a static vulnerability marker of schizophrenia that reflects early neurodevelopmental abnormality.

Gray matter changes in subjects at high risk for developing psychosis and first-episode schizophrenia: a voxel-based structural MRI study

Objectives: The aim of the present study was to use a voxel-based magnetic resonance imaging method to investigate the neuroanatomical characteristics in subjects at high risk of developing psychosis compared with those of healthy controls and first-episode schizophrenia patients. Methods: This study included 14 subjects with at-risk mental state (ARMS), 34 patients with first-episode schizophrenia, and 51 healthy controls. We used voxel-based morphometry with the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra tools to investigate the whole-brain difference in gray matter volume among the three groups. Results: Compared with the healthy controls, the schizophrenia patients showed significant gray matter reduction in the left anterior cingulate gyrus. There was no significant difference in the gray matter volume between the ARMS and other groups. Conclusion: The present study suggests that alteration of the anterior cingulate gyrus may be associated with development of frank psychosis. Further studies with a larger ARMS subjects would be required to examine the potential role of neuroimaging methods in the prediction of future transition into psychosis.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic–pituitary–adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes.

Increased Frontal Gyrification Negatively Correlates with Executive Function in Patients with First-Episode Schizophrenia

Abstract Previous neuroimaging studies of gyrification, a possible marker of early neurodevelopment, in schizophrenia patients have reported inconsistent results. In addition, it remains unclear whether aberrant gyrification in schizophrenia patients, if present, is associated with cognitive impairment, which is one of the core features of schizophrenia. Magnetic resonance images were obtained from 62 patients with first‐episode schizophrenia and 57 healthy control subjects. Using FreeSurfer software, local gyrification index (LGI) of the entire cortex was compared between the groups. The relationship between LGI and performance in the Wisconsin Card Sorting Test (WCST) was also examined in a subgroup of patients (n= 28). Compared with the controls, the patients showed a significantly higher LGI in a wide range of bilateral frontal regions as well as in the right inferior parietal and bilateral occipital regions. The number of WCST categories archived in patients was negatively correlated with the LGI mainly in the rostral middle frontal and anterior cingulate regions in the right hemisphere. Our findings suggested a widespread hypergyrification pattern in schizophrenia patients, which supported early neurodevelopmental abnormalities. Our results also suggested that executive dysfunction in schizophrenia patients may be at least partly related to aberrant neurodevelopment, especially in the right frontal regions.

Longitudinal MRI study of the pituitary volume in chronic schizophrenia: A preliminary report

This longitudinal MRI study investigated the pituitary volume in 17 patients with chronic schizophrenia and 17 matched controls. In contrast to previous findings of pituitary expansion during the first episode of schizophrenia, the chronic patients showed non-significant mild pituitary atrophy, suggesting that the pituitary volume changes differently at different illness stages.

Longitudinal MRI study of the midline brain regions in first-episode schizophrenia

This magnetic resonance imaging (MRI) study investigated the prevalence and size of the adhesio interthalamica (AI) and cavum septi pellucidi (CSP) in 64 first-episode schizophrenia patients and 64 controls, of whom longitudinal data were available for 20 patients and 21 controls. The AI was shorter in the patients and showed longitudinal decline in both groups; there was also a trend for AI atrophy to correlate with negative symptoms. The CSP showed no group difference. These results suggest a role for the AI as a possible neurodevelopmental marker of schizophrenia.

The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects

Increasing evidence has implicated the role of Disrupted-in-Schizophrenia-1 (DISC1), a potential susceptibility gene for schizophrenia, in early neurodevelopmental processes. However, the effect of its genotype variation on brain morphologic changes related to neurodevelopmental abnormalities in schizophrenia remains largely unknown. This magnetic resonance imaging study examined the association between DISC1 Ser704Cys polymorphism and a range of brain neurodevelopmental markers [cavum septi pellucidi (CSP), adhesio interthalamica (AI), olfactory sulcus depth, and sulcogyral pattern (Types I, II, III, and IV) in the orbitofrontal cortex (OFC)] in an all Japanese sample of 75 schizophrenia patients and 87 healthy controls. The Cys carriers had significantly larger CSP than the Ser homozygotes for both schizophrenia patients and healthy controls. The Cys carriers also exhibited a reduction in the Type I pattern of the right OFC in the healthy controls, but not in the schizophrenia patients. The DISC1 Ser704Cys polymorphism did not affect the AI and olfactory sulcus depth in either group. These results suggested a possible role of the DISC1 genotype in the early neurodevelopment of human brains, but failed to show its specific role in the neurodevelopmental pathology of schizophrenia.