Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study.

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.     

Structural brain abnormalities in patients with schizophrenia and their healthy siblings

OBJECTIVE: The authors sought to investigate the contribution of genotype on structural brain abnormalities in schizophrenia. METHOD: Intracranial volumes and volumes of the cerebrum, white and gray matter, lateral and third ventricles, frontal lobes, caudate nucleus, amygdala, hippocampus, parahippocampal gyrus, and the cerebellum were measured in 32 same-sex siblings discordant for schizophrenia and 32 matched comparison subjects by means of magnetic resonance imaging. RESULTS: Third ventricle volumes did not differ between the schizophrenic patients and their healthy siblings. However, both had higher third ventricle volumes than did the comparison subjects. The schizophrenic patients had lower cerebrum volumes than did the comparison subjects, whereas the cerebrum volume of the healthy siblings did not significantly differ from the patients or comparison subjects. Additionally, patients with schizophrenia displayed a volume reduction of the frontal lobe gray matter and a volume increase of the caudate nuclei and lateral ventricles compared to both their healthy siblings and comparison subjects. Intracranial volume, CSF volume, or volumes of the cerebellum, amygdala, hippocampus, or the parahippocampal gyrus did not significantly differ among the patients, siblings, and comparison subjects. CONCLUSIONS: Healthy siblings share third ventricle enlargement with their affected relatives and may partially display a reduction in cerebral volume. These findings suggest that third ventricular enlargement, and to some extent cerebral volume decrease, may be related to genetic defects that produce a susceptibility to schizophrenia.     

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.     

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho = 0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho = 0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.     

Olanzapine increases grey and white matter volumes in the caudate nucleus of patients with schizophrenia

There are inconsistent reports regarding the caudate nucleus volume in patients with schizophrenia compared with healthy subjects. The reason for this is that neuroleptic medication may affect the volume of the caudate nucleus in schizophrenic patients. To clarify which antipsychotic medication changes the volume of the caudate nucleus in patients with schizophrenia, we measured the volumes of grey and white matter in the caudate nucleus of schizophrenic patients. Ten patients with schizophrenia were examined twice by magnetic resonance imaging (MRI) to measure the grey and white matter volumes in the caudate nucleus. After the first MRI examination, all the patients were treated with olanzapine. The clinical responses were evaluated by the positive and negative rating scale. When the symptoms improved, the patients were examined by a second MRI scan. Ten healthy control subjects also underwent MRI. The schizophrenic patients had reduced volumes of grey and white matter in the caudate nucleus compared to the healthy control subjects. The volumes of grey and white matter in the caudate nucleus of the schizophrenic patients increased after treatment with olanzapine. These findings suggest that treatment with olanzapine may increase the grey and white matter volumes in the caudate nucleus in patients with schizophrenia.     

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.     

Altered white matter/gray matter proportions in the striatum of patients with schizophrenia: a volumetric MRI study

OBJECTIVE: Anatomical structures of the striatum were studied in 58 patients with schizophrenia and 56 healthy comparison subjects of both genders matched for age and handedness. METHOD: Magnetic resonance imaging scans were used to measure gray matter, white matter, and CSF volumes of the caudate, putamen, and nucleus accumbens in the left and the right hemispheres. RESULTS: White matter/gray matter ratios of the striatal structures were significantly lower in patients than in healthy subjects. In patients, relative white matter volumes in the caudate and nucleus accumbens were reduced, whereas gray matter in the putamen was increased. The total accumbens volume did not differ by diagnosis, but left side accumbens was larger than right in the healthy subjects. The proportion of white matter was greater in women in both the patient and healthy comparison groups. Total caudate and putamen volumes demonstrated no differences due to diagnosis or laterality, but a negative correlation was found in patients between white matter volumes and increasing age. There were no significant correlations among total striatal volumes, white matter/gray matter ratios, age at onset of illness, or illness duration. An estimate of lifetime neuroleptic consumption was positively correlated with right gray matter volume of the putamen in male schizophrenia patients who received typical neuroleptics. CONCLUSIONS: The proportion of white matter to gray matter tissue volumes of the caudate, putamen, and nucleus accumbens is altered in medicated chronic schizophrenia patients, but the total volumes are unchanged.     

Localized volume reduction in prefrontal, temporolimbic, and paralimbic regions in schizophrenia: an MRI parcellation study

Functional and structural abnormalities of the anterior cingulate gyrus (ACG) in patients with schizophrenia have been repeatedly reported. However, one remaining issue is whether gray matter volume reduction in ACG exists to an extent comparable with, or even in excess of, that in other prefrontal and temporolimbic regions. High-spatial-resolution magnetic resonance imaging was performed on patients with schizophrenia (n=27) and on age-, gender-, and parental socioeconomic-status-matched healthy control subjects (n=27). After the gray and white matter were semiautomatically segmented, whole prefrontal and temporal lobes were manually parceled into 15 subregions-by-two hemispheres (30 regions of interest) constituting seven prefrontal gray matter regions, six temporal gray matter regions, the prefrontal white matter, and the temporal white matter. Compared with healthy subjects, schizophrenic patients showed significant gray matter volume reduction in the bilateral ACG, this being the largest effect size (left, 0.84; right, 0.56) among all the regions examined. There were also significant gray matter volume reductions in the bilateral posterior STG, bilateral inferior frontal gyrus, left posterior amygdala-hippocampal complex (mostly hippocampus), and the left insula. These results suggest that gray matter volume reductions in the ACG are prominent among prefrontal and temporolimbic regions in patients with schizophrenia. These findings indicate the importance of ACG abnormalities in the pathophysiology of schizophrenia.     

Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression

Early emotional stress is associated with a life-long burden of risk for later depression and stressful life events contribute to the development of depressive episodes. In this study we investigated whether childhood stress is associated with structural brain alterations in patients with major depression (MD). Forty-three patients with MD and 44 age as well as gender matched healthy control subjects were investigated using high-resolution magnetic resonance imaging (MRI). Region of interest analysis of the hippocampus, whole brain voxel-based morphometry (VBM) and assessment of childhood stress was carried out. Significantly smaller hippocampal white matter and prefrontal gray matter volume was observed in patients with MD compared to healthy controls. In particular left hippocampal white matter was smaller in patients, who had emotional childhood neglect, compared to those without neglect. For male patients this effect was seen in the left and right hippocampus. Moreover, physical neglect during childhood affected prefrontal gray matter volume in healthy subjects. Both emotional neglect and brain structural abnormalities predicted cumulative illness duration and there was a significant interaction between emotional neglect and prefrontal volumes as well as hippocampal white matter on the illness course. Childhood neglect resulted in hippocampal white matter changes in patients with major depression, pronounced at the left side and in males. Most interestingly, childhood stress and brain structure volumes independently predicted cumulative illness course. Subjects with both, structural brain changes and childhood emotional neglect seem to be at a very high risk to develop a more severe illness course.     

Hippocampal size and dementia in stroke patients: the Sydney stroke study

BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.     

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.     

Voxel-based morphometry of patients with schizophrenia or bipolar I disorder: a matched control study

Controlled trials provide critical tests of hypotheses generated by meta-analyses. Two recent meta-analyses have reported that gray matter volumes of schizophrenia and bipolar I patients differ in the amygdala, hippocampus, or perigenual anterior cingulate. The present magnetic resonance imaging study tested these hypotheses in a cross-sectional voxel-based morphometry (VBM) design of 17 chronic schizophrenia and 15 chronic bipolar patients and 21 healthy subjects matched for age, gender and duration of illness. Whole brain gray matter volume of both the schizophrenia and bipolar groups was smaller than among healthy control subjects. Regional voxel-wise comparisons showed that gray matter volume was smallest within frontal and temporal regions of both patient groups. Region of interest analyses found moderately large to large differences between schizophrenia and healthy subjects in the amygdala and hippocampus. There were no group differences in the perigenual anterior cingulate. When schizophrenia and bipolar groups were directly compared, the schizophrenia group showed smaller gray matter volumes in right subcortical regions involving the right hippocampus, putamen, and amygdala. The hippocampal and amygdala findings confirm predictions derived from recent meta-analyses. These structural abnormalities may be important factors in the differential manifestations of these two functional psychotic disorders.     

Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia

We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n=23) with the healthy controls (n=38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p=0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p<0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia.     

Grey matter volume in adolescents with anorexia nervosa and associated eating disorder symptoms

Anorexia nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN; however, differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of adolescent girls with AN before and after weight recovery and the relationship of any changes with clinical characteristics. We collected high‐resolution T1‐weighted images from 26 underweight girls with AN before weight gain and 20 healthy control volunteers. Clinical features were assessed using the Eating Disorder Examination Questionnaire. AN subjects displayed reduced grey matter volumes in the insula, amygdala, prefrontal, hippocampal and cingulate cortices and the precuneus, relative to healthy controls. In a subset of 10 AN subjects who were followed after weight recovery, grey matter volumes increased to near‐control levels in the orbito‐ and medial prefrontal, insular, left hippocampal and mid‐ and posterior cingulate cortices and precuneus. The recovery of the right anterior thalamus and the left orbitofrontal cortex was correlated with improvements in eating concerns and shape concerns, respectively. However, large parts of the anterior cingulate cortex, caudate nuclei and right hippocampus did not display any grey matter recovery following a short‐term of treatment. These results show that in adolescents with AN, some brain regions display marked recovery in grey matter volume following weight recovery, whereas others do not, considering grey mater recovery possibly linked to symptom improvement.     

Hippocampus and amygdalar volumes in patients with somatization disorder

In regard to somatization disorder which covers an important section of our patient population, there is no systematic structural magnetic resonance imaging (MRI) study in the literature. Therefore, we aimed to use structural MRI to evaluate the hippocampus amygdalar complex which is associated with both stress and regulation of emotion that are main basis clinical presentation of somatization disorder in the patients with somatization disorder. Totally 40 subjects (20 patients with somatization disorder and 20 healthy controls) were enrolled. Intracranial volume (ICV), whole brain volume, gray and white matter volumes, and hippocampus and amygdalar volumes of the subjects were measured. In regard to unadjusted mean volumes of measured structures, the patients had significantly smaller mean volumes of the left and right amygdala. However, two groups did not differ significantly in terms of whole brain, total gray and white matter or hippocampus volumes. The repeated measures ANCOVA predicting left and right amygdala volumes demonstrated a significant main effect of diagnostic group. In conclusion, the findings of the present study revealed that the patients with somatization disorder had significantly smaller mean volumes of the left and right amygdala without any differences in regard to whole brain, total gray and white matter or hippocampus volumes. On the basis of the current findings, it seems reasonable to evaluate that abnormalities in connectivity and/or metabolism dimensions and to examine the effects of drugs or psychotherapeutic approaches could be especially informative.     

Anterior hippocampal volume reduction in male patients with schizophrenia

Quantitative high resolution magnetic resonance imaging (MRI) was utilized to measure anterior, posterior, and total hippocampal volumes in 27 male patients with chronic schizophrenia and 24 male controls. To optimize measurement techniques, hippocampal volumes were: (1) acquired with 1.4-mm slices; (2) excluded with the amygdala; (3) normalized for position; and (4) corrected for total intracranial volume (ICV). The results of a linear mixed effects regression analysis, which made it possible to analyze total anterior and total posterior hippocampal volumes separately, indicated that the anterior hippocampus was significantly smaller in the schizophrenic group relative to the control group. There were no significant group differences with respect to posterior hippocampal volumes, and no significant correlations between hippocampal volumes and illness duration. A significant lateralized asymmetry was also noted in both groups with the right hippocampal volume being larger than the left. These preliminary findings support a significant anterior hippocampal volume reduction in men with schizophrenia as well as a similar hippocampal volume asymmetry in both male controls and schizophrenics.     

Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.

The purpose of this study was to examine the relationship between phosphorus magnetic resonance spectroscopy (31P MRS) parameters and left prefrontal volumes in both patients with schizophrenia and healthy subjects. 31P MRS parameters and magnetic resonance imaging (MRI) volumetric data were collected in the left prefrontal region in 10 patients with schizophrenia and 10 healthy subjects of comparable age, handedness, sex, educational level, and parental educational level. No correlations were found between any MRS parameter and grey matter volumes in the combined subjects. Phosphomonoester (PME) and grey matter volumes, however, were both correlated negatively with age. PMEs were found to be decreased, and calculated intracellular magnesium ([Mg2+]intra) was found to be increased in the patients with schizophrenia compared with healthy subjects after adjusting for left prefrontal grey and white matter, total brain volume, and age. These findings suggest that cortical grey and white manner volumes are not directly related to PME and [Mg2+]intra abnormalities in schizophrenia patients.     

Reduced white matter volume of the caudate nucleus in patients with schizophrenia

To examine volumetric abnormality, the caudate nucleus was measured in patients with schizophrenia and healthy subjects using magnetic resonance imaging. The absolute and relative volumes of white matter in the caudate nucleus were found to be significantly smaller in patients with schizophrenia compared to those in healthy subjects. There were significant correlations between dosages of neuroleptics during the previous year and absolute gray matter volumes of the caudate nucleus as well as relative white matter volumes in patients with schizophrenia. These findings suggest that reduced white matter volume of the caudate nucleus may be a factor affecting the abnormal connectivity of the corticostriatal loop, and that neuroleptic medication would be related to white matter alteration in patients with schizophrenia. Our result replicates a previous study reporting that there is a lack of negative correlation between age and caudate nucleus volume. We also suggest that the disease process of schizophrenia might interfere with normal aging.     

Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study

OBJECTIVE: The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects. METHOD: Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects. RESULTS: There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS: These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.     

Effects of age on prefrontal subregions and hippocampal volumes in young and middle‐aged healthy humans

There are limited data available regarding the effects of age and sex on discrete prefrontal gray and white matter volumes or posterior and anterior hippocampal volumes in healthy humans. Volumes of the superior frontal gyrus, anterior cingulate gyrus, and orbital frontal lobe were computed manually from contiguous magnetic resonance (MR) images in 83 (39M/44F) healthy humans (age range = 16–40) and segmented into gray and white matter. Volumes of the posterior and anterior hippocampal formation were also computed with reliable separation of the anterior hippocampal formation from the amygdala. There were significant age‐by‐tissue type interactions for the superior frontal gyrus and orbital frontal lobe such that gray matter within these regions correlated significantly and inversely with age. In contrast, no significant age effects were evident within regional white matter volumes. Analysis of hippocampal volumes indicated that men had larger volumes of the anterior, but not posterior hippocampal formation compared to women even following correction for total brain size. These data highlight age effects within discrete prefrontal cortical gray matter regions in young and middle aged healthy humans and suggest that the white matter comprising these regions may be more resistant to age effects. Furthermore, understanding the potential role of sex and age in mediating prefrontal cortical and hippocampal volumes may have strong relevance for psychiatric disorders such as schizophrenia that have implicated neurodevelopmental abnormalities within frontotemporal circuits in their pathogenesis. Hum Brain Mapp 34:2129–2140, 2013. © 2012 Wiley Periodicals, Inc.