Altered neural basis of self-reflective processing in schizophrenia: An fMRI study.

BACKGROUND: Impaired self-awareness has often been described in schizophrenia. Recent neuroimaging studies examining the self-reflection processes in schizophrenia have produced inconsistent results. METHOD: We examined the self-reflective neural network using self- and other-evaluation tasks in schizophrenia. Fifteen schizophrenia patients and fifteen age- and sex-matched healthy subjects underwent functional magnetic resonance imaging. Subjects were required to decide whether the sentence described their own personal trait (self-evaluation) and that of their close friends (other-evaluation). RESULTS: Unlike normal control subjects, the schizophrenia patients did not have greater activation of the left posterior cingulate gyrus and hippocampus during self-evaluation than during other-evaluation. On the other hand, the schizophrenia patients had higher activation of the right superior frontal and right supramarginal gyri during self-evaluation than control subjects. Only the patient group exhibited hyperactivation in the left hippocampus and right external capsule associated with the other-evaluation task. CONCLUSIONS: These findings provide evidence for an altered neural basis of self-reflective processing, which may underlie the self-awareness deficits in schizophrenia.

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.

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.

Insular cortex volume in established bipolar affective disorder: a preliminary MRI study.

This structural magnetic resonance imaging study investigated insular cortex volume in 26 patients with bipolar I disorder and 24 matched controls. While insular volume did not differ between these groups, exploratory analyses demonstrated that the number of depressive episodes correlated negatively with the anterior insular volume in the patients, suggesting it may have a role in the pathophysiology of bipolar disorder.

A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia.

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 unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7 years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: -2.8%/year; right: -1.5%/year) compared with the schizotypal patients (left: -0.6%/year; right: -0.3%/year) and controls (left: 0.0%/year; right: -0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Volumetric MRI study of the insular cortex in individuals with current and past major depression.

BACKGROUND: Functional neuroimaging studies have implicated the insular cortex in emotional processing, including the evaluation of one's own emotion, as well as in the neurobiology of major depressive disorder (MDD). Nevertheless, it remains largely unknown whether MDD patients exhibit morphologic changes of the insular cortex, and whether such changes reflect state or trait markers of the disorder. METHODS: We delineated the anterior and posterior insular cortices using magnetic resonance imaging in 29 currently depressed patients (mean age=32.5 years, 7 males), 27 remitted depressed patients (mean age=35.1 years, 9 males), and 33 age- and gender-matched healthy control subjects (mean age=34.0 years, 12 males). RESULTS: Both current and remitted MDD patients showed significant volume reduction of the left anterior insular cortex as compared with healthy controls, but there was no group difference in the posterior insular cortex volume. Insular volumes did not correlate with the severity of depressive symptoms. Furthermore, the presence of melancholia and co-morbidity with anxiety disorders did not affect insular cortex volumes. LIMITATIONS: Although there was no difference in the insular cortex volume between medicated and unmedicated patients, a comprehensive investigation of medication effects was not possible, as complete data (e.g., dose, duration) were not available. CONCLUSIONS: These findings suggest that the morphologic abnormality of the anterior insular cortex, which plays a major role in introspection and emotional control, may be a trait-related marker of vulnerability to major depression, supporting the notion that MDD involves pathological alterations of limbic and related cortical structures.

Insular cortex volume and impulsivity in teenagers with first-presentation borderline personality disorder.

Fronto-limbic neural dysfunction has been implicated in the emotional dysregulation and impulsivity seen in borderline personality disorder (BPD). However, it remains unclear whether affected individuals exhibit morphologic changes of the insular cortex, a fronto-limbic integration cortex engaged in emotional regulation and impulse control. This magnetic resonance imaging study examined the insular cortex volume and its relationship to clinical characteristics in a first-presentation teenage BPD sample. No significant difference was found in the insular volume between 20 BPD participants (5 males) and 20 healthy control participants (5 males). There was no association between the insular volume and parasuicidal episodes, trauma exposure, or comorbid Axis I disorders, but the BPD participants with violent episodes during the previous 6 months had a smaller insular volume bilaterally compared with those without such episodes. Furthermore, right anterior insular volume in the BPD participants was negatively correlated with impulsivity score. These preliminary findings suggest that insular cortex volume does not significantly differ in early BPD, but that there might be a relationship with violent and impulsive behavior that is often seen in the disorder. Further studies are needed to clarify whether the potential relationship between the insular cortex volume and impulsivity is specific to BPD.

Insular cortex gray matter changes in individuals at ultra-high-risk of developing psychosis.

Morphologic abnormalities of the insular cortex have been described in psychotic disorders such as schizophrenia, but it remains unclear whether these changes predate the onset of psychosis or develop progressively over the course of illness. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the long and short insular cortices in 97 neuroleptic-naïve individuals at ultra-high-risk (UHR) for developing psychosis [of whom 31 (32%) later developed psychosis (UHR-P) and 66 (68%) did not (UHR-NP)] and 55 age- and gender-matched healthy comparisons. We also conducted a longitudinal comparison of the insular cortex gray matter changes in 31 UHR individuals (20 UHR-NP and 11 UHR-P) and 20 controls for whom follow-up MRI data between 1 and 4 years later were available. In the cross-sectional comparison, the UHR-P subjects had a significantly smaller insular cortex compared with the UHR-NP subjects bilaterally and with the controls on the right hemisphere, especially for the short insular region. More severe negative symptoms in UHR-P subjects at baseline were associated with smaller volumes of the right long insular cortex. In the longitudinal comparison, the UHR-P subjects showed greater gray matter reduction of insular cortex bilaterally (-5.0%/year) compared with controls (-0.4%/year) or UHR-NP subjects (-0.6%/year). Our findings suggest that insular cortex gray matter abnormalities in psychotic disorders may reflect pre-existing vulnerability, but that there are also active progressive changes of the insular cortex during the transition period into psychosis. Whether these longitudinal changes are features of the disorder or related to treatment with antipsychotic medication remains to be determined.

Diagnostic specificity of the insular cortex abnormalities in first-episode psychotic disorders.

Volume reductions of the insular cortex have been described in schizophrenia, but it remains unclear whether other psychotic disorders such as affective psychosis also exhibit insular cortex abnormalities. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the anterior (short) and posterior (long) insular cortices in 162 first-episode patients with various psychotic disorders (46 schizophrenia, 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses) and 62 age- and gender-matched healthy comparison subjects. Patients with schizophrenia showed bilateral volume reduction of the anterior and posterior insular cortices compared with controls, but the remaining first-episode psychosis subgroups had normal insular volumes. The volumes of these insular subregions were significantly smaller in schizophrenia patients than in patients with schizophreniform disorder or affective psychoses. There was no association between the insular cortex volume and daily dosage or type of antipsychotic medication in any patient group. These findings suggest that the widespread volume reduction of the insular cortex is specific to established schizophrenia, implicating its role in the neurobiology of clinical characteristics associated with schizophrenia.

Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia.

Morphologic abnormalities of the insular cortex have been described in psychotic disorders such as schizophrenia, but it remains unknown whether these abnormalities develop progressively over the course of the illness. In the current study, longitudinal magnetic resonance imaging data were obtained from 23 patients with first-episode psychosis (FEP), 11 patients with chronic schizophrenia, and 26 healthy controls. The volumes of the short (anterior) and long (posterior) insular cortices were measured on baseline and follow-up (between 1 and 4 years later) scans and were compared across groups. In cross-sectional comparison at baseline, the FEP and chronic schizophrenia patients had significantly smaller short insular cortex than did controls. In longitudinal comparison, the FEP patients showed significant gray matter reduction of the insular cortex over time (-4.3%/2.0 years) compared with controls (0.3%/2.2 years) without significant subregional effects, but there was no difference between chronic schizophrenia patients (-1.7%/2.4 years) and controls. The gray matter loss of the left insular cortex over time in FEP patients was correlated with the severity of positive and negative symptoms at follow-up. These findings indicate that patients with psychotic disorders have smaller gray matter volume of the insular cortex especially for its anterior portion (short insula) at first expression of overt psychosis, but also exhibit a regional progressive pathological process of the insular cortex during the early phase after the onset, which seems to reflect the subsequent symptomatology.

Prevalence and length of the adhesio interthalamica in schizophrenia spectrum disorders.

We used magnetic resonance imaging to investigate the prevalence and length of the adhesio interthalamica (AI) in 72 schizophrenia patients, 47 schizotypal disorder patients, and 81 healthy controls. The AI was more often absent and shorter in both disorders than in controls, possibly reflecting common neurodevelopmental abnormalities in the schizophrenia spectrum.

Association between absence of the adhesio interthalamica and amygdala volume in schizophrenia.

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in schizophrenia, but not consistently replicated. We investigated the prevalence and anterior-posterior length of the AI in 62 schizophrenia patients (32 males, 30 females) and 63 healthy controls (35 males, 28 females) using magnetic resonance imaging. We also explored the relation between the AI and volumetric measurements for the third ventricle, medial temporal structures (amygdala, hippocampus, and parahippocampal gyrus), superior temporal sub-regions, and frontal lobe regions (prefrontal area and anterior cingulate gyrus). The AI was absent in 24.2% (15/62) of the schizophrenia patients and in 9.5% (6/63) of the controls, showing a significant group difference. For the length of the AI, schizophrenia patients had a shorter AI than controls, and males had a shorter AI than females. The subjects without an AI had a significantly larger third ventricle and smaller parahippocampal gyrus than the subjects with an AI for both groups. We found a significant diagnosis-by-AI interaction for the amygdala. The schizophrenia patients without an AI had a smaller bilateral amygdala than those with an AI, whereas the AI was not associated with the volume of the amygdala in the control subjects. These findings suggest that the absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia.

Prevalence of large cavum septi pellucidi and its relation to the medial temporal lobe structures in schizophrenia spectrum.

Magnetic resonance imaging was used to evaluate the prevalence of the cavum septi pellucidi (CSP) in 154 schizophrenia patients, 47 schizotypal disorder patients, and 163 healthy controls. We also explored the relation of a large CSP (> or =6 mm) with medial temporal lobe structures. No significant difference was found in the prevalence of the CSP (76.0% of the schizophrenia patients, 81.6% of the controls, and 85.1% of the schizotypal patients) or the large CSP (6.5% of the schizophrenia patients, 7.4% of the controls, and 10.6% of the schizotypal patients) among the groups, but patients with a large CSP (10 schizophrenia and 5 schizotypal patients) had smaller volumes of bilateral amygdala and left posterior parahippocampal gyrus than patients without it. In the control subjects, the large CSP did not affect the volumes of the medial temporal lobe structures. These findings might reflect neurodevelopmental abnormalities in midline and associated limbic structures of the brain in schizophrenia spectrum.

Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: a preliminary report.

A longer duration of untreated psychosis (DUP) in schizophrenia is reported to lead to a poorer clinical outcome, possibly reflecting a neurodegenerative process after the onset of overt psychosis. However, the effect of DUP on brain morphology in schizophrenia is still poorly understood. In this study, we used magnetic resonance imaging to investigate the relation between DUP and volumetric measurements for the superior temporal sub-regions (Heschl's gyrus, planum temporale, and caudal superior temporal gyrus), the medial temporal lobe structures (hippocampus and amygdala), and the frontal lobe regions (prefrontal area and anterior cingulate gyrus) in a sample of 38 schizophrenia patients (20 males and 18 females) whose illness duration was less than five years. We found a significant negative correlation between DUP and the volume of gray matter in the left planum temporale even after controlling for age, age at illness onset, and duration and dosage of neuroleptic medication. There was no such correlation for the other brain regions including each sub-region of the prefrontal cortex (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus). When subjects were divided into two groups around the median DUP, the long-DUP group had a significantly smaller planum temporale gray matter than the short-DUP group. These findings may reflect a progressive pathological process in the gray matter of the left planum temporale during the initial untreated phase of schizophrenia, whereas abnormalities in the medial temporal regions might be, as has been suggested from previous longitudinal findings, relatively static at least during the early course of the illness.

Temporal lobe gray matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri.

Although several brain morphologic studies have suggested abnormalities in the temporal regions to be a common indicator of vulnerability for the schizophrenia spectrum, less attention has been paid to temporal lobe structures other than the superior temporal gyrus or the medial temporal region. In this study, we investigated the volume of gray matter in the fusiform gyrus, the parahippocampal gyrus, the middle temporal gyrus, and the inferior temporal gyrus using magnetic resonance imaging in 39 schizotypal disorder patients, 65 schizophrenia patients, and 72 age and gender matched healthy control subjects. The anterior fusiform gyrus was significantly smaller in the schizophrenia patients than the control subjects but not in the schizotypal disorder patients, while the volume reduction of the posterior fusiform gyrus was common to both disorders. Volumes for the middle and inferior temporal gyri or the parahippocampal gyrus did not differ between groups. These findings suggest that abnormalities in the posterior region of the fusiform gyrus are, as have been suggested for the superior temporal gyrus or the amygdala/hippocampus, prominent among the temporal lobe structures as a common morphologic substrate for the schizophrenia spectrum, whereas more widespread alterations involving the anterior region might be associated with the development of full-blown schizophrenia.

Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum.

Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal pole (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis.

Volumetric MRI study of the short and long insular cortices in schizophrenia spectrum disorders.

We have previously reported volume reductions of the insular cortex in schizophrenia, but it is still not clear whether insular cortex volume loss preferentially involves the anterior (short insular cortex) or posterior (long insular cortex) portion. On the other hand, no volumetric studies of the brain have examined changes in insular cortex volume in subjects with schizotypal features. In this study, we separately investigated the volumes of the short and long insular cortex portions using magnetic resonance imaging in 37 schizotypal disorder patients (24 males, 13 females), 62 schizophrenia patients (32 males, 30 females), and 69 healthy controls (35 males, 34 females). While the volumes of the short and long insular cortex were significantly reduced in schizophrenia patients compared with schizotypal disorder patients and control subjects, there was no difference between schizotypal disorder patients and control subjects. These results suggest that the volume reduction of the insular cortex may be specific to overt schizophrenia without topographically specific localization.