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Structural magnetic resonance imaging studies provide evidence for sex differences in the human brain. Differences in surface area and the proportion of gray to white matter volume are observed, in particular in the parietal lobe. To our knowledge, no studies have examined sex differences in parietal lobe structure in younger populations or in the context of development. The present study evaluated sex differences in the structure of the parietal lobe in children aged 7 to 17 years. In addition, by adding a cohort of previously studied adults aged 18 to 50 years, sex differences in parietal lobe structure were examined across the age span of 7 to 50 years. Compared with the adult sample, the younger sample showed that the ratio of parietal lobe cortex to white matter was greater in female brains, but no sex differences in surface area. When examining the effects of age, surface area exhibited a significant sex-age interaction. In male brains, there was essentially no decrease in surfaces area over time, whereas in female brains, there was a significant decrease in surface area over time. These findings support the notion of structural sex differences in the parietal lobe, not only in the context of cross-sectional assessment but also in terms of differences in developmental trajectories., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

Background: A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC., Case Presentation: B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance., Conclusions: The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process.

Objective: To assess the long-term outcome of brain structure in preterm infants, at an average age of 12 years, who received a red blood cell transfusion for anemia of prematurity., Design: As neonates, this cohort of infants participated in a clinical trial in which they received red blood cell transfusions based on a high pretransfusion hematocrit threshold (liberal group) or a low hematocrit threshold (restricted group). These 2 preterm groups were compared with a group of full-term healthy control children., Setting: Tertiary care hospital., Participants: Magnetic resonance imaging scans for 44 of the original 100 subjects were obtained., Intervention: Liberal vs restricted transfusion., Main Outcome Measures: Intracranial volume, total brain tissue, total cerebrospinal fluid, cerebral cortex and cerebral white matter volume, subcortical nuclei volume, and cerebellum volume., Results: Intracranial volume was substantially smaller in the liberal group compared with controls. Intracranial volume in the restricted group was not different from controls. Whole-cortex volume was not different in either preterm group compared with controls. Cerebral white matter was substantially reduced in both preterm groups, more so for the liberal group. The subcortical nuclei were substantially decreased in volume, equally so for both preterm groups compared with controls. When sex effects were evaluated, the girls in the liberal group had the most significant abnormalities., Conclusion: Red blood cell transfusions affected the long-term outcome of premature infants as indicated by reduced brain volumes at 12 years of age for neonates who received transfusions using liberal guidelines.

Objective: To evaluate potential abnormalities in brain structure of children and adolescents with unilateral clefts., Design: Case-control study., Setting: Tertiary care center., Participants: Boys aged 7 to 17 years with right (n=14) and left (n=19) clefts were compared with healthy age-matched boys (n=57)., Main Exposures: Structural brain measures were obtained using magnetic resonance imaging., Outcome Measure: It was explored whether laterality of clefts had a significant effect on brain structure. To this end, volumes of tissue types and various brain regions were evaluated., Results: Total white matter was significantly lower in boys with right clefts compared with boys with left clefts and healthy boys. Gross regional analyses demonstrated that reductions in white matter were evident in both the cerebellum and the cerebrum in boys with right clefts. Furthermore, within the cerebrum, white matter volumes were particularly low in the frontal lobes and the occipital lobes., Conclusions: These preliminary results suggest that right clefts may be associated with more abnormalities in brain structure. More generally, laterality of a birth defect may have a significant effect on a developing organism.

Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.

Females have been shown in a number of studies to be more adept in social perception compared with males. In addition, studies have reported that brain regions important in interpretation of nonverbal social cues, such as the ventral frontal cortex (VFC), are morphologically different between genders. To investigate the relationship between the structure of the VFC and social cognition, gray matter volume and surface area of the VFC were measured on magnetic resonance imaging (MRI) scans from 30 men and 30 women matched for age and IQ. The VFC was subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). The SG, but not the OFC, was proportionately larger in women. A subset of subjects was administered the Interpersonal Perception Task (IPT), a test of social perceptiveness, and the Personal Attributes Questionnaire (PAQ), a scale of femininity and masculinity. Identification with more feminine traits on the PAQ correlated with greater SG gray matter volume and surface area. In addition, higher degrees of femininity correlated with better performance on the IPT. Taken together, these data suggest a complex relationship between femininity, social cognition, and the structure of the SG.

Objective: Cortical morphology was evaluated in subjects with known gene expansion for Huntington's disease and no manifest disease., Method: Magnetic resonance imaging scans were obtained for 24 subjects with preclinical Huntington's disease and were compared to those for 24 matched healthy subjects by means of novel imaging methods to quantify aspects of cortical structure., Results: In relation to the comparison subjects, those with preclinical Huntington's disease showed altered cortex morphology with enlargement of gyral crowns and abnormally thin sulci. These changes were manifested in global alterations of gyral and sulcal shape., Conclusion: These findings lend support to the notion that, in addition to the degenerative process, abnormal neural development may also be an important process in the pathoetiology of Huntington's disease.

Objective: To evaluate brain structure in a sample of children with isolated clefts of the lip and/or palate (ICLP)., Design: Case-control study., Setting: Tertiary care center., Participants: A large sample of 74 children aged 7 to 17 years with ICLP was compared with a healthy control group, matched by age and sex., Main Exposure: Isolated cleft lip and/or palate., Outcome Measures: General measures of height and head circumference were obtained. Brain structure was evaluated using magnetic resonance imaging, generating both general and regional brain measures (volumes)., Results: Height was significantly lower in the ICLP group (F = 4.83, P = .03). After controlling for this smaller body size, children with ICLP had abnormally small brains with both cerebrum (F = 4.47, P = .04) and cerebellum (F = 14.56, P <.001) volumes substantially decreased. Within the cerebrum, the frontal lobe was preferentially decreased (F = 7.22, P = .008) and subcortical nuclei were also substantially smaller (F = 4.18, P = .003). Tissue distribution of cortical gray matter and white matter within the cerebrum were abnormal in boys with ICLP (larger cortical volume, smaller volume of white matter) but proportional to controls in girls with ICLP., Conclusions: Children with ICLP have abnormal brain structure, potentially due to abnormal brain development. The fact that the pattern of brain abnormalities in children with ICLP is dramatically different from the pattern of brain abnormalities seen in adults with ICLP suggests that brain growth and development trajectory is also abnormal in subjects with ICLP.

Objective: A variety of findings have implicated the portion of the anterior cingulate cortex ventral to the corpus callosum in the pathophysiology of familial depressive disorder. There are, as yet, few data to address the specificity of these abnormalities to depressive disorders or to characterize their stability over time., Method: The authors studied 10 subjects who were judged to have had major depressive disorder with psychotic features, who underwent magnetic resonance imaging (MRI) protocols, and who participated in a longitudinal study of recent-onset psychosis. These were group-matched to 10 subjects with schizophrenia and to 10 well comparison subjects. Volumetric measures were made of the posterior and anterior portions of the subgenual prefrontal cortex for these 30 subjects. Follow-up scans done an average of 4 years after intake were available for seven subjects with major depressive disorder, nine subjects with schizophrenia, and five well comparison subjects., Results: Volumes of the left side of the posterior subgenual prefrontal cortex differed significantly by group and were smallest for the group with psychotic major depressive disorder. Volumes of the anterior subgenual prefrontal cortex did not differ significantly by group. Patients with major depressive disorder were more likely to show increases in posterior subgenual prefrontal cortex volume on follow-up than were comparison subjects or patients with schizophrenia., Conclusions: These findings add to the evidence that abnormalities in the subgenual region of the anterior cingulate play a role in at least some types of mood disorder.

This study compares globus pallidus (GP) volume between neuroleptic naive patients with schizophrenia and healthy controls using structural MRI. The volume of the external segment of the GP (GPe) was positively correlated with the severity of global symptoms, as measured by the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms (SANS/SAPS, Andreasen and Olsen, 1982). The volume for the GP, GPe, and internal segment (GPi) did not differ between groups.

Background: The insular cortex is a limbic integration region engaged in emotional and cognitive functions. Previously, we found that neuroleptic-naive subjects had abnormally small insular volumes compared with control subjects, with volume directly related to severity of psychotic symptoms., Methods: To further investigate insular cortex abnormalities and their functional correlates, we measured insular gray matter volume and cortical surface size, using magnetic resonance images among 30 patients with schizophrenia and a matched control group. The sample was designed to represent a variety of phenomenologic profiles to provide sufficient variance in multiple measures, including severity of illness and exposure to neuroleptics (typical only)., Results: There were no significant differences in morphology between patients and control subjects; however, among patients, psychotic symptoms were inversely correlated with insular volume, replicating our previous finding in neuroleptic-naive subjects. Neuroleptic exposure had a specific effect on insular morphology: increasing drug exposure (measured in dose-years) correlated with larger insular volume., Conclusions: This effect of neuroleptic exposure might account for the lack of difference in structural measures in this more chronic sample, whereas the initial study on neuroleptic-naive subjects showed group differences. Further research is needed to investigate the potential relationship between changes in insula volume from neuroleptic exposure and clinical outcome.

Background: Changes in the volume of the caudate nucleus over time in patients with schizophrenia has been shown to be directly related to neuroleptic exposure. Few studies have evaluated caudate volume in subjects with schizophrenia who were neuroleptic naive at intake and treated exclusively with atypical neuroleptics., Methods: Fourteen patients were matched by gender to 14 healthy controls and were evaluated over time using MRI. The patients were neuroleptic naïve at intake and at follow-up had been treated exclusively with atypical neuroleptics. Difference scores were calculated for caudate volumes. Neuroleptic exposure was quantified using a dose-years formula., Results: There was no difference between patients and controls in the amount of change over time in the volume of the caudate. However, the female patients had a negative correlation (r= - 0.74) between drug exposure and volume change while the male patients had a positive correlation (r = 0.63). Therefore, there was a significant gender effect on the relationship between atypical neuroleptic exposure and changes in the structure of the caudate over time (test for difference in correlations: z = 2.39, p = 0.016)., Conclusions: The change in caudate nucleus volume over time with exposure to atypical neuroleptics may be sex-dependent. Atypical neuroleptic expsoure was associated with volume increase over time in the males, while exposure in females was associated with volume decrement over time.

Background: Many studies have shown that structural brain abnormalities in schizophrenia are already present by the time of index evaluation of first-episode patients. However, whether these abnormalities progressively worsen during the subsequent course of the disorder remains unresolved., Methods: To study the longitudinal progression of structural brain abnormalities, high-resolution multispectral magnetic resonance images obtained on 73 recent-onset schizophrenic patients and 23 controls were analyzed using state-of-the-art, well-validated, and highly reliable neuroimaging tools. The mean duration between initial and follow-up MRIs was 3 years. Repeated-measures analysis of covariance was carried out to determine (1) whether brain volume changes differed between patients and controls and (2) the significance of regional brain changes on functional outcome in schizophrenia., Results: We found accelerated enlargement in cortical sulcal cerebrospinal fluid spaces early in the course of schizophrenia. Instead of the usual trajectory of volume enlargement, patients showed progressive reduction in frontal lobe white matter volume. A reciprocal increase in frontal lobe cerebrospinal fluid volume also occurred at a more rapid rate in patients than in controls. In keeping with most of our a priori hypotheses, patients with poor outcome had greater lateral ventricular enlargement over time than patients with good outcome. Progressive decrement in frontal lobe white matter volume and enlargement in frontal lobe cerebrospinal fluid volume were associated with greater negative symptom severity. Reductions in frontal lobe gray and white matter volumes correlated with poorer executive functioning., Conclusions: There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment. These progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment. Disruptions in neurodevelopment or neural plasticity may act alone or in combination to bring about these progressive brain deficits in schizophrenia.

Objective: Studies suggest the presence of premorbid cognitive impairment in patients with schizophrenia, yet the onset and course of these deficits remain unclear. The purpose of this study was to investigate the longitudinal course of premorbid cognitive functioning in individuals with schizophrenia by using prospective data obtained from scholastic test results., Method: Scores from grades 4, 8, and 11 on the Iowa Tests of Basic Skills and the Iowa Tests of Educational Development were obtained for 70 subjects who later developed schizophrenia. The mean percentile rank of the subjects' scores in the areas of vocabulary, reading comprehension, language, mathematics, sources of information, and an overall composite category were compared with state norms., Results: The subjects scored below the 50th percentile for each category in all three grades, but only language, reading, sources of information, and composite scores from grade 11 were significantly below state norms. With regard to longitudinal course, there was a significant linear decrease in language scores over time. Scores from grade 11 were positively correlated with WAIS-R IQ, verbal fluency, and Rey Auditory Verbal Learning scores at first illness episode. Scores from grade 11 were not significantly correlated with age at illness onset or ratings of disorganized, psychotic, or negative symptoms., Conclusions: Scholastic test scores at grades 4 and 8 were nonsignificantly below average in this group of children who later developed schizophrenia. However, test scores dropped significantly between grades 8 and 11. This corresponds to ages 13-16 years, or the onset of puberty. Poor or declining scholastic performance may be a precursor to the cognitive impairment seen during the first episode of illness.

Cognitive deficits have been well-documented in children with non-syndromic clefts of the lip and/or palate. However, no study to date has formally assessed cognition in adults with oral clefts. This study was designed to evaluate neuropsychological functioning in adult males with non-syndromic clefts of the lip and/or palate (n=50) compared to age and sex-matched controls. Subjects with oral clefts were found to have significantly lower full scale IQ, performance IQ and verbal IQ scores compared to their matched controls. After controlling for IQ, patients showed specific deficits in verbal fluency. Adult males with oral clefts manifest a specific pattern of cognitive deficits. As the development of the face is highly interdependent with the development of the brain, it is theorized that the etiology of these cognitive deficits is a primary problem with abnormal brain development.