Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI study

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.     

Bilateral volume reduction of the insular cortex in patients with schizophrenia: a volumetric MRI Study

The morphologic changes of the insular cortex have been described in schizophrenia, but with inconsistencies between reports. We investigated the insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males, 31 females). The insular cortex volume was measured on consecutive coronal 1-mm slices. Volumes of the left and right insular cortex were significantly reduced in schizophrenia patients compared with control subjects. There were no effects of gender on the insular cortex volume in the patient group or control subjects. Bilateral insular cortex volumes were correlated negatively with illness duration in the patient group. The findings of this study suggest that there is a possible progressive loss of the gray matter volume of the bilateral insular cortices subsequent to the onset of schizophrenia.     

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.     

Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder

Lack of normal structural asymmetry of the anterior cingulate gyrus (ACG) in patients with schizophrenia has been reported in our previous study. However, to our knowledge, no morphological studies of the brain have examined changes in ACG volume in patients with schizotypal features. We investigated the volume of the gray matter and the white matter of the ACG by three-dimensional magnetic resonance imaging (MRI) in 24 patients who met the ICD-10 criteria for schizotypal disorder (12 males, 12 females) in comparison with 48 age- and gender-matched healthy control subjects (24 males, 24 females) and 40 patients with schizophrenia (20 males, 20 females). As we reported previously, right ACG gray matter volume was significantly reduced in the female patients with schizophrenia compared with the female controls. On the other hand, the gray and white matter volume of the ACG in the patients with schizotypal disorder did not differ significantly from the values in the healthy controls or the patients with schizophrenia. However, the female patients with schizotypal disorder showed a lack of right-greater-than-left asymmetry of the ACG gray and white matter found in the female controls. These results suggest that both schizotypal and schizophrenic subjects share, at least in part, the same cerebral asymmetry abnormalities. Received: 28 May 2002 / Accepted: 30 October 2002 Correspondence to T. Takahashi     

The relationship between prefrontal brain volume and characteristics of memory strategy in schizophrenia spectrum disorders

The present study investigated the relationship between memory strategy use and prefrontal gray/white matter volumes of healthy control subjects, patients with schizophrenia or schizotypal disorder. Gray/white matter volumes were measured for the superior, middle, inferior, ventral medial and orbital prefrontal regions, using high-resolution magnetic resonance (MR) images that were acquired from 35 patients with schizophrenia, 25 patients with schizotypal disorder and 19 healthy subjects. Participants were also administered the Japanese Verbal Learning Test (JVLT). In control subjects, larger left inferior frontal and straight gyrus's gray matter volumes were associated with higher semantic clustering rates on the JVLT, and smaller left inferior frontal gray matter volumes were associated with higher serial clustering ratio. In schizophrenic patients, smaller left orbitofrontal gray matter volumes were associated with lower semantic clustering rates on the JVLT. In schizotypal patients, smaller left inferior frontal white matter volume was associated with smaller serial clustering rates and larger semantic clustering rate. These findings suggest that semantic organization in schizophrenic patients might depend on mobilization of a memory strategy that is mediated by orbitofrontal cortex functioning. Failure to use a semantic organization strategy might be related to reduced volume in the inferior frontal gyrus. The findings for schizotypal patients suggest a compensation mechanism to remember the words using a serial processing strategy is at work when the inferior frontal gyrus cannot mediate semantic processing.     

Lack of normal gender differences of the perigenual cingulate gyrus in schizophrenia spectrum disorders

Abstract. We have previously reported a lack of normal gender differences of the perigenual cingulate gyrus in patients with schizophrenia. The purpose of this study was to examine the perigenual cingulate gyrus morphology in patients with schizotypal disorder. We investigated volume of the gray and white matter of the perigenual cingulate gyrus in 26 patients with schizotypal disorder (14 males, 12 females) in comparison with 61 age- and gender-matched healthy controls (30 males, 31 females) and 58 schizophrenia patients (31 males, 27 females) using magnetic resonance imaging. The volumetric measures of the perigenual cingulate gyrus were compared among the three groups that were entered into the same multiple analysis of variance model. The gray and white matter volume of the perigenual cingulate gyrus in the schizotypal patients did not differ significantly from the values in the healthy controls or the schizophrenia patients. Similar to schizophrenia, however, the schizotypal patients showed a lack of normal gender differences of the perigenual cingulate gray matter seen in the healthy controls (females > males). These results suggest that both schizotypal and schizophrenia patients may share the same disruption of the normal pattern of gender differences of the perigenual cingulate gyrus.     

Parietal lobe volume deficits in schizophrenia spectrum disorders

There has been little attention given to whether parietal lobe structural deficits are present in patients with schizophrenia and related personality disorders. The current study was designed to examine parietal volume alterations between schizophrenia and schizotypal personality disorder. Twenty-five patients with schizotypal disorder, 53 patients with schizophrenia, and 59 healthy volunteers were scanned using high-resolution magnetic resonance imaging (MRI). Volume measurements of the postcentral gyrus (PoCG), precuneus, superior parietal gyrus (SuPG), supramarginal gyrus (SMG), and angular gyrus (AGG) were performed on consecutive 1-mm coronal slices. Gray matter volumes were reduced in all parietal subregions in patients with schizophrenia compared with healthy controls. White matter volumes were also reduced in the SuPG and PoCG. In contrast, the schizotypal subjects had gray matter reductions only in the PoCG, while other regions were not affected. In addition, there was a lack of normal significant-leftward asymmetry in the SMG in schizophrenia. These findings demonstrate that volume reductions in the somatosensory cortices are common morphological characteristics in schizophrenia spectrum disorders. The additional volume alterations in schizophrenia may support the notion that a deficit in the posterior parietal region is critical for the manifestation of overt psychotic symptoms.     

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.     

Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.

OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.     

Insular volume reduction in schizophrenia

Structural and functional abnormalities of the insular cortex have been reported in patients with schizophrenia. Most studies have shown that the insular volumes in schizophrenia patients are smaller than those of healthy people. As the insular cortex is functio-anatomically divided into anterior and posterior subdivisons, recent research is focused on uncovering a specific subdivisional abnormality of the insula in patients with schizophrenia. A recent ROI-based volumetric MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients (Makris N, Goldstein J, Kennedy D, Hodge S, Caviness V, Faraone S, Tsuang M, Seidman L (2006) Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res 83:155-171). On the other hand, our VBM-based volumetric study revealed a reduction in right posterior insular volume (Yamada M, Hirao K, Namiki C, Hanakawa T, Fukuyama H, Hayashi T, Murai T (2007) Social cognition and frontal lobe pathology in schizophrenia: a voxel-based morphometric study. NeuroImage 35:292-298). In order to address these controversial results, ROI-based subdivisional volumetry was performed using the MRI images from the same population we analyzed in our previous VBM-study. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. Patients with schizophrenia showed a global reduction in insular gray matter volumes relative to healthy comparison subjects. In a simple comparison of the volumes of each subdivision between the groups, a statistically significant volume reduction in patients with schizophrenia was demonstrated only in the right posterior insula. This study suggests that insular abnormalities in schizophrenia would include anterior as well as posterior parts. Each subdivisional abnormality may impact on different aspects of the pathophysiology and psychopathology of schizophrenia; these relationships should be the focus of future research.     

Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis

CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia. OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis. DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization. SETTING: Inpatient units at a private psychiatric hospital. PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects. MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated. RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes. CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.     

Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder

OBJECTIVE: Individuals with schizophrenia spectrum disorders evince similar genetic, neurotransmitter, neuropsychological, electrophysiological, and structural abnormalities. Magnetic resonance imaging (MRI) studies have shown smaller gray matter volume in patients with schizotypal personality disorder than in matched comparison subjects in the left superior temporal gyrus, an area important for language processing. In a further exploration, the authors studied two components of the superior temporal gyrus: Heschl's gyrus and the planum temporale. METHOD: MRI scans were acquired from 21 male, neuroleptic-naive subjects recruited from the community who met DSM-IV criteria for schizotypal personality disorder and 22 male comparison subjects similar in age. Eighteen of the 21 subjects with schizotypal personality disorder had additional comorbid, nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on coronal images with subsequent identification of Heschl's gyrus and the planum temporale. Exploratory correlations between region of interest volumes and neuropsychological measures were also performed. RESULTS: Left Heschl's gyrus gray matter volume was 21% smaller in the schizotypal personality disorder subjects than in the comparison subjects, a difference that was not associated with the presence of comorbid axis I disorders. There were no between-group volume differences in right Heschl's gyrus or in the right or left planum temporale. Exploratory analyses also showed a correlation between poor logical memory and smaller left Heschl's gyrus volume. CONCLUSIONS: Smaller left Heschl's gyrus gray matter volume in subjects with schizotypal personality disorder may help to explain the previously reported abnormality in the left superior temporal gyrus and may be a vulnerability marker for schizophrenia spectrum disorders.     

Gray matter features of schizotypal disorder patients exhibiting the schizophrenia-related code types of the Minnesota Multiphasic Personality Inventory

OBJECTIVE: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia-related code types have the morphological brain abnormalities associated with schizophrenia. METHOD: Voxel-based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia-related code types of the MMPI and 28 normal individuals. RESULTS: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls. CONCLUSION: Our findings suggest that STD patients with the schizophrenia-related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.     

MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder

OBJECTIVE: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. METHOD: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. RESULTS: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. CONCLUSIONS: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.     

Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume

Alterations, sometimes sex-dependent, in volumes and gyral structure of areas of cerebral cortex have been reported in schizophrenia. Such changes imply an anomaly of connectivity. The gyrification, percentage of tissue volume attributed to white matter, cortical volume and white matter volume were measured from magnetic resonance images in males and females with (n = 61) and without (n = 42) schizophrenia. The frontal, temporal and an amalgam of occipital and parietal lobes were examined in both hemispheres. There was no effect of schizophrenia on the gyrification of the brain. For the volume of occipito-parietal white matter, females with schizophrenia had bilaterally lower volumes, while males with schizophrenia had greater volumes than controls. It is concluded that the changes in connectivity underlying the pathogenesis of schizophrenia are sex-specific and expressed in occipito-parietal white matter.     

Deficient attentional modulation of the startle response in patients with schizotypal personality disorder

OBJECTIVE: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. METHOD: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. RESULTS: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. CONCLUSIONS: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with 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.     

An MRI study of superior temporal gyrus volume in women with schizotypal personality disorder

OBJECTIVE: An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder. METHOD: The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29). RESULTS: There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction between hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech. CONCLUSIONS: This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left-right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately.     

Insular volumes in first-episode schizophrenia: gender effect

Insula is a multimodal sensory integration region that acts as a gateway between somatosensory areas and limbic structures such as amygdala. Only a handful of region of interest (ROI) studies have suggested insular volume reduction in patients with schizophrenia but none have documented a gender effect on the volume of this structure. The authors used magnetic resonance images to measure insular volumes in previously untreated patients with first-episode schizophrenia (N=30) relative to those of healthy comparison subjects (N=30). Correlations with symptom severity were carried out. Intracranial volume was used as a covariate in the analysis. Female patients (N=15) had significantly reduced right insular volume relative to healthy female comparison subjects (p<0.05). On preliminary analysis, the right and left insular volumes in female patients had significant negative correlations with the positive symptoms scores (p<0.05), but not on correcting for multiple comparisons. Insula is developmentally and phylogenetically a watershed region where the more primitive allocortex transitions into the more developed isocortex. Thus its role as a substrate of neurodevelopmental hypothesis in schizophrenia and the interplay with gender deserves more attention.     

A volumetric MRI study of the entorhinal cortex in first episode neuroleptic-naive schizophrenia.

BACKGROUND: Imaging studies have frequently reported volume loss of limbic structures in schizophrenia, yet there appears to be no quantitative data on entorhinal cortex volumes in patients with neuroleptic naive first-episode schizophrenia. METHODS: The volume of the entorhinal cortices of 22 control subjects and 18 patients with neuroleptic-na?ve first-episode schizophrenia were measured from magnetic resonance images (MRI) scans using recently designed anatomic criteria for MRI anatomy of the entorhinal cortex. RESULTS: Smaller entorhinal volumes were found bilaterally in the schizophrenic patients. This volume loss did not correlate with items on the Positive and Negative Syndrome Scale. CONCLUSIONS: These data suggest early involvement of the entorhinal cortex in schizophrenia.