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• In a first of its kind, this study used advanced brain imaging analyses on high dimensional 7 Tesla images from 92 Cannabis Users and 92 age- matched Non Users from the Human connectome study. We examined the impact of cannabis smoking on the brain networks in grey matter and white matter and psychological function. • We found that cannabis users had altered corticocerebellar functional connectivity mirrored in aberrant decision making with intriguing correlations between these modalities. Decision-making (DM) impairments are important predictors of cannabis initiation and continued use. In cannabis users, how decision-making abnormalities related to structural and functional connectivity in the brain are not fully understood. We employed a three-method multimodal image analysis and multivariate pattern analysis (MVPA) on high dimensional 7 tesla MRI images examining functional connectivity, white matter microstructure and gray matter volume in a group of cannabis users and non-users. Neuroimaging and cognitive analyses were performed on 92 CU and 92 age- matched NU from a total of 187 7T scans. CU were selected on the basis of their scores on the Semi-Structured Assessment for the Genetics of Alcoholism. The groups were first compared on a decision-making test and then on ICA based functional connectivity between corticocerebellar networks. An MVPA was done as a confirmatory analysis. The anatomy of these networks was then assessed using Diffusion Tensor imaging (DTI) and cortical volume analyses. Cannabis Users had significantly higher scores on the Iowa Gambling task (IGT) [Gambling task Percentage larger] and significantly lower scores on the [Gambling task reward Percentage smaller]. Left accumbens (L NAc) volume was significantly larger in cannabis users. DTI analysis between the groups yielded no significant (FWE corrected) differences. Resting state FC analysis of the left Cerebellum region 9 showed enhanced functional connectivity with the right nucleus accumbens and left pallidum and left putamen in CU. In addition, posterior cerebellum showed enhanced functional connectivity (FWE corrected) with 2 nodes of the DMN and left and right paracingulate (sub genual ACC) and the sub callosal cortex in CU. IGT percentage larger scores correlated with posterior cerebellar functional connectivity in non-user women. A multivariate pattern analysis confirmed this cerebellar hyperconnectivity in both groups. Our results demonstrate for the first time that deficits in DM observed in cannabis users are mirrored in hyper connectivity in corticocerebellar networks. Cortical volumes of some of the nodes of these networks showed increases in users. However, the underlying white matter was largely intact in CU. The observed DM deficits and hyper connectivity in resting networks may contribute to difficulties in quitting and/or facilitating relapse. [ABSTRACT FROM AUTHOR]

Background The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relatives; and healthy control subjects. Methods We present findings from morphometric and neurocognitive analyses of 1381 subjects (SZ probands, n = 224; PBD probands, n = 190; schizoaffective disorder probands, n = 142; unaffected relatives, n = 483 [SZ relatives, n = 195; PBD relatives, n = 175; schizoaffective disorder relatives, n = 113]; control subjects, n = 342). Magnetization prepared rapid acquisition gradient-echo T1 scans across five sites were obtained using 3-tesla magnets. Image processing was done using FreeSurfer Version 5.1. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia scale. Results Anterior and posterior splenial volumes were significantly reduced across the groups. The SZ and PBD probands showed robust and significant reductions, whereas relatives showed significant reductions of intermediate severity. The splenial volumes were positively but differentially correlated with aspects of cognition in the probands and their relatives. Proband groups showed a significant age-related decrease in the volume of the anterior splenium compared with control subjects. Among the psychosis groups, the anterior splenium in probands with PBD showed a stronger correlation with psychotic symptoms, as shown by the Positive and Negative Syndrome Scale. All five subregions showed significantly high familiality. Conclusions The splenial volumes were significantly reduced across the psychosis dimension. However, this volume reduction impacts cognition and clinical manifestation of the illnesses differentially. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Smaller hippocampal volumes similar to those found in schizophrenia (SZ) are frequently observed to a lesser extent in non-psychotic first-degree relatives of patients with the illness, compared to control subjects. In this study, subdivisions of the hippocampal formation and their association with verbal and visual learning and memory were assessed in persons at familial high risk (FHR) for SZ. Methods: MRI scans were acquired using a 3T Siemens scanner of young adult (ages 19–32) FHR subjects (N=46) and controls with no family history of illness (i.e., at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. Subfields of the hippocampal formation were evaluated using the van Leemput method (Van Leemput et al., 2010). Learning and memory measures were collected by standardized neurocognitive tests. Results: Controlling intracranial volume, significantly reduced left (p<0.025), and right hippocampus (p<0.024) volumes were observed in FHR subjects. Among the subfields, the left (p<0.01) and right subicula (p<0.005) were significantly reduced in the FHR group. Immediate verbal recall of stories was significantly impaired and was significantly correlated with the left and right subicula within the FHR group. Conclusions: Reduced subiculum volume and its association with verbal memory refines further the association with left and right hippocampus reported in previous FHR studies of schizophrenia. Further research is needed to determine the specific genetic and environmental risk factors that may be related to hippocampal subfield alterations. [Copyright &y& Elsevier]

Abstract: Alterations in white matter (WM) may be seen in young relatives at risk and may underlie vulnerability to schizophrenia. We were interested in exploring which of the WM regions were altered in adolescent offspring at familial risk for schizophrenia. We examined structural alterations in the offspring of subjects with schizophrenia or schizoaffective disorder (HR; n=65; 36 males) and healthy controls (HC; n=80: 37 males) matched for age and education. MRI images were collected using a GE 1.5T scanner at the University of Pittsburgh Medical Center. Image processing was done using FreeSurfer (MGH) by an experienced rater blind to clinical data. We used multivariate analysis of covariance, with intracranial volume (p>0.05) and age as covariates. High Risk offspring had significant reductions in total WM, hemispheric WM and WM within left parietal and left cingulate cortices. Male offspring had more pronounced right hemisphere WM reductions than females. [Copyright &y& Elsevier]

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with neurocognitive impairments. The neural substrates of cognitive impairments in 22q11DS remain poorly understood. Because the corpus callosum (CC) is found to be abnormal in a variety of neurodevelopmental disorders, we obtained volumetric measurements of the CC and its subregions, examined the relationship between these regions and neurocognition and selected genotypes within candidate genes in the 22q11.2 interval in 59 children with 22q11DS and 53 control subjects. The total CC, splenium and genu were significantly larger in children with 22q11DS and the enlargement was associated with better neurocognitive functioning in the 22q11DS group, suggestive of a compensatory increase in the CC volumes. The expected age-related increase in the volume of the CC was not seen in children with 22q11DS, indicative of dysmaturation of the CC in these children. The increased volumes in the genu, splenium and total CC in the 22q11DS group were associated with polymorphisms within the candidate genes: COMT (rs4680), ZDHHC8 (rs175174) and UFD1L (rs5992403). These findings indicate that alterations in the CC volume in children with 22q11DS are associated with cognition and specific genotypes in the 22q11.2 interval. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Neuroanatomical and cognitive alterations typical of schizophrenia (SZ) patients are observed to a lesser extent in their adolescent and adult first-degree relatives, likely reflecting neurodevelopmental abnormalities associated with genetic risk for the illness. The anatomical pathways for language are hypothesized to be abnormal and to underlie the positive symptoms of schizophrenia. Examining non-psychotic relatives at high familial risk (FHR) for schizophrenia may clarify if these deficits represent trait markers associated with genetic vulnerability, rather than specific markers resulting from the pathological process underlying schizophrenia. Methods: T1 MRI scans from a 3T Siemens scanner of young adult FHR subjects (N=46) and controls with no family history of illness (i.e. at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. We explored volumetric and lateralization alterations in regions associated with language processing. An extensive neuropsychological battery of language measures was administered. Results: No significant differences were observed between groups on any language measures. Controlling intracranial volume, significantly smaller left pars triangularis (PT) (p<0.01) and right pars orbitalis (PO) (p<0.01) volumes and reversal of the L>R pars orbitalis (p<0.001) lateralization were observed in FHR subjects. In addition, the L pars triangularis and R pars orbitalis correlated with performance on tests of linguistic function in the FHR group. Conclusions: Reduced volume and reversed structural asymmetry in language-related regions hypothesized to be altered in SZ are also found in first degree relatives at FHR, despite normal language performance. To clarify if these findings are endophenotypes for Sz, future studies would need to be performed of ill and well family members no longer within the age range of risk for illness to show these deficits segregate with schizophrenia within families. Moreover, measures of complex language need to be studied to determine if FHR individuals manifest impairments in some aspects of language function. [Copyright &y& Elsevier]

Abstract: Alterations in the structure of the corpus callosum (CC) have been observed in schizophrenia. Offspring of schizophrenia parents have 10–15 times higher risk for developing schizophrenia. We examined CC volume in offspring at genetic high-risk (HR) subjects. Since the sub-regions of the CC are topographically mapped to cortical brain regions, we hypothesized that HR subjects may show a decrement in total volume and differential volume decreases in sub-regions of the CC. The offspring of schizophrenia parents (HR; n =70; 36 males) and healthy volunteers with no family or personal history of psychotic disorders (healthy controls (HC); n =73; 37 males) matched for age, gender and education were selected for the study. Magnetic resonance images were collected using a GE 1.5T scanner and processed using FreeSurfer image analysis software. The CC was divided into five neuroanatomically based partitions. The volume of total CC and the five sub-regions were measured blind to clinical information. With covariation for intracranial volume, HR subjects had significantly reduced total CC, more prominently observed in the anterior splenium. An age-related increase in CC volume was found in the anterior and posterior splenium of healthy controls but not in HR subjects. The volume reduction was greater in male than female HR subjects. The volume reduction in the CC may reflect a reduction in axonal fibers crossing the hemispheres and/or myelination between the left and right temporo-parietal cortices. The absence of an age-related volume increase suggests an abnormal developmental trajectory that may underlie susceptibility to schizophrenia. [Copyright &y& Elsevier]

Abstract: Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N =60) and healthy controls (HC; N =42) using verbal fluency tests and Freesurfer to process T1-MRI scans. We hypothesized volumetric and lateralization alterations of the PT and their correlation with verbal fluency deficits. HR subjects had letter verbal fluency deficits (controlling for IQ), left PT deficits (p =.00), (controlling ICV) and reversal of the L>R PT asymmetry noted in HC. Right Heschl''s (p =.00), left supramarginal (p =.00) and right angular gyrii (p =.02) were also reduced in HR subjects. The L>R asymmetry of the Heschl''s gyrus seen in HC was exaggerated and asymmetries of L>R of supramarginal and R>L of angular gyri, seen in HC were attenuated in HR subjects. L>R asymmetry of the PT predicted better verbal fluency across the pooled HR and HC groups. Young relatives of schizophrenia patients have verbal fluency deficits, gray matter volume deficits and reversed asymmetry of the pars triangularis. A reversed structural asymmetry of the PT in HR subjects may impair expressive language abilities leading to verbal fluency deficits. Volumetric deficits and altered asymmetry in inferior parietal and Heschl''s gyrii may accompany genetic liability to schizophrenia. [Copyright &y& Elsevier]

Se planteó la hipótesis de que la corteza de asociación heteromodal participa de forma selectiva en la fisiopatología de la esquizofrenia. Para examinar esta hipótesis, los autores midieron los volúmenes de la corteza prefrontal parietal inferior y de la circunvolución temporal superior y examinaron el sistema de conexiones entre estas regiones. Método: Se incluyeron en el estudio 44 pacientes con esquizofrenia o trastorno esquizoafectivo y 34 individuos sanos de control. Para la evaluación morfométrica de la corteza de asociación heteromodal se utilizó una toma de gradiente eco tridimensional en la secuencia equilibrada de imágenes por resonancia magnética. Resultados: Los pacientes con esquizofrenia se caracterizaron por unos volúmenes de la región prefrontal inferior significativamente menores y una inversión significativa de la asimetría normal de la corteza parietal inferior. No se detectaron diferencias de grupo significativas para el volumen de la circunvolución temporal superior. Los grupos difirieron, significativamente, en la correlación entre los volúmenes de la región prefrontal inferior y los volúmenes de la circunvolución angular. Conclusiones: Los resultados indican que los pacientes con esquizofrenia se caracterizan por determinadas anomalías selectivas de las regiones heteromodales implicadas en la neuroanatomía del lenguaje. [ABSTRACT FROM PUBLISHER]

Objective: The heteromodal association cortex has been hypothesized to be selectively involved in the pathophysiology of schizophrenia. To test this hypothesis, the authors measured prefrontal, inferior parietal, and superior temporal gyrus volumes and examined the pattern of connections among these regions. Method: Forty-four patients with schizophrenia or schizoaffective disorder and 34 healthy comparison subjects were included in the study. A spoiled gradient recall acquisition in the steady-state three-dimensional magnetic resonance imaging sequence was used for morphometric assessment of the heteromodal association cortex. Results: Patients with schizophrenia had significantly smaller inferior prefrontal region volumes and significant reversal of the normal asymmetry of the inferior parietal cortex. No significant group differences were found in superior temporal gyrus volume. The groups differed significantly in the correlation between inferior prefrontal region volumes and angular gyrus volumes. Conclusions: The results suggest that patients with schizophrenia may be characterized by selective abnormalities of the heteromodal regions involved in the neuroanatomy of language. [ABSTRACT FROM AUTHOR]

Abstract: Grey-matter volumetric and cognitive deficits in young, high-risk relatives of schizophrenia patients may be vulnerability markers of the illness. Although these markers may be correlated, it is unclear if their distributions in relatives overlap. We examined convergence of these markers in 94 young first and second-degree relatives (HR) and 81 healthy controls. Subjects were assessed using WCST, CPT-IP and Benton–Hamscher tests and on grey-matter volumes of brain regions related to language, attention and executive function using FreeSurfer to process T1-MR-images. K-means clustering using cognitive performance scores split relatives into sub-samples with better (HR+C, n =35) and worse (HR-C, n =59) cognition after controlling for age and gender. All regional volumes and language related regional laterality-indices were compared between HR-C, HR+C and control subjects, controlling for age, gender and intra-cranial volume. Volumes of caudate nuclei, thalami, hippocampi, inferior frontal gyri, Heschl''s gyri, superior parietal cortices, supramarginal gyri, right angular gyrus, right middle frontal gyrus and right superior frontal gyrus, leftward laterality of supramarginal and inferior frontal gyri and rightward laterality of the angular gyrus were reduced in HR-C compared to controls. Volumes of Heschl''s gyri, left supramarginal gyrus, inferior frontal gyri, hippocampi and caudate nuclei HR-C were smaller in HR-C compared to HR+C. HR+C showed deficits compared to controls only for the superior parietal and right angular volumes. Premorbid neuroanatomical and laterality alterations in schizophrenia may selectively manifest in cognitively compromised relatives. Overlapping structural and cognitive deficits may define a hyper vulnerable sub-sample among individuals at familial predisposition to schizophrenia. [Copyright &y& Elsevier]

Schizophrenia can be classified into two separate syndromes: deficit and nondeficit. Primary, enduring negative symptoms are used to define the deficit form of the illness, which is believed to have a unique neurobiological substrate. Previous research suggests that an aberrant prefrontal–thalamic–parietal network underlies deficit schizophrenia. In this study we conducted diffusion tensor imaging (DTI) fiber tracking to assess the integrity of the superior longitudinal fasciculus (SLF), the major white matter tract that connects prefrontal and parietal cortical regions, in deficit and nondeficit people with schizophrenia. We also used proton magnetic resonance spectroscopy (1H-MRS) to assess neurochemistry in the left middle prefrontal and left inferior parietal cortical regions. A total of 20 subjects with schizophrenia (10 deficit and 10 nondeficit) and 11 healthy subjects participated in this study. Results revealed reduced fractional anisotropy (FA), an index of white matter integrity, in the right hemisphere SLF and frontal white matter in the deficit subjects. There were no differences in MRS metabolite concentrations among groups. To our knowledge, this is the first DTI study to show compromised integrity of the major white matter tract that connects frontal and parietal regions in deficit schizophrenia. These findings provide further support for altered frontal–parietal network in deficit schizophrenia.Neuropsychopharmacology (2009) 34, 1514–1522; doi:10.1038/npp.2008.207; published online 3 December 2008 [ABSTRACT FROM AUTHOR]

Objective: The study examined gray matter volume across psychosis diagnoses organized by dimensional and DSM-IV categories from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) sample. Method: In total, 351 probands with psychosis (146 with schizophrenia, 90 with schizoaffective disorder, and 115 with psychotic bipolar I disorder), 369 of their first-degree relatives (134 were relatives of individuals with schizophrenia, 106 of individuals with schizoaffective disorder, and 129 of individuals with psychotic bipolar I disorder), and 200 healthy comparison subjects were assessed. Gray matter volumes from 3-T T1-weighted images were analyzed using the VBM8 toolbox for SPM8, and outcomes were determined at a false discovery rate-corrected threshold of p,0.005. Results: Across the psychosis dimension, probands (N=351) and relatives with psychosis spectrum disorders (N=34) showed substantial overlapping gray matter reductions throughout the neocortex, whereas relatives without psychosis spectrum (N=332) had normal gray matter volumes relative to comparison subjects. Across DSM-IVdiagnoses, schizophreniaandschizoaffective probands showed overlapping gray matter reductions in numerous cortical and subcortical regions, whereas psychotic bipolar probands showed limited gray matter reductions localized to the frontotemporal cortex relative to comparison subjects. All relative groups had gray matter volumes that did not differ from comparison subjects. Conclusions: Across the dimensional psychosis categories, these findings indicate extensive neocortical gray matter reductions in psychosis probands and relatives with psychosis spectrum disorders, possibly reflecting lifetime psychosis burden, but normal gray matter in nonpsychotic relatives. Traditional DSM-IV psychosis grouping revealed partially divergent gray matter phenotypes for probands with schizophrenia or schizoaffective disorder (extensive neocortical or subcortical gray matter reductions) relative to those with psychotic bipolar disorder (smaller reductions were limited to frontotemporal regions). The dimensional conceptualization of psychosis appears useful in defining more homogenous disease categories that may help identify underlying psychosis biomarkers and develop a biologically driven diagnostic system and targeted treatments [ABSTRACT FROM AUTHOR]

Abstract: Background: Proton magnetic resonance spectroscopy (1H MRS) enables in-vivo measurement of several relevant brain metabolites and has provided evidence of a range of neurochemical abnormalities in schizophrenia, especially in glutamate and N-acetyl-aspartate (NAA). While individuals at high familial risk for schizophrenia (HR) exhibit some neurobiological findings observed in the disorder, 1H MRS findings and their clinical correlates are not well characterized in this population. Methods: We compared 23 adolescent and young adult offspring of schizophrenia patients with 24 age- and sex-matched healthy controls using 1H MRS. We acquired multi-voxel, short TE 1H MRS measurements at 1.5T and obtained metabolite concentrations of N-acetyl-aspartate (NAA), combined glutamate and glutamine (Glu+Gln) and choline-containing compounds (GPC+PC) for the left and right thalamus, anterior cingulate gyrus, and caudate. We also assessed the relationship between regional metabolite levels, clinical measures and brain volume in a subset of 16 high-risk and 15 control subjects. Results: Compared to healthy controls, high-risk subjects showed reductions in NAA levels in all three regions (thalamus, caudate, and anterior cingulate cortex), increases in Glu+Gln in the thalamus and caudate, and increases in GPC+PC in the anterior cingulate. In HR, thalamic Glu+Gln concentration was positively correlated and thalamic NAA inversely correlated with measures of schizotypy. Anterior cingulate GPC+PC and caudate Glu+Gln were significantly correlated with attenuated psychotic symptom severity. Anterior cingulate NAA was correlated with executive function. Conclusions: Our data suggest the occurrence of metabolic alterations in young relatives of schizophrenia patients similar to those seen in patients with established illness. The observed correlations with cognitive deficits and psychosis-related psychopathology suggest that these metabolic measures may have value as biomarkers of risk for schizophrenia. [Copyright &y& Elsevier]

Abstract: This study sought to examine whole brain and regional gray matter (GM) phenotypes across the schizophrenia (SZ)–bipolar disorder psychosis dimension using voxel-based morphometry (VBM 8.0 with DARTEL segmentation/normalization) and semi-automated regional parcellation, FreeSurfer (FS 4.3.1/64 bit). 3T T1 MPRAGE images were acquired from 19 volunteers with schizophrenia (SZ), 16 with schizoaffective disorder (SAD), 17 with psychotic bipolar I disorder (BD-P) and 10 healthy controls (HC). Contrasted with HC, SZ showed extensive cortical GM reductions, most pronounced in fronto-temporal regions; SAD had GM reductions overlapping with SZ, albeit less extensive; and BD-P demonstrated no GM differences from HC. Within the psychosis dimension, BD-P showed larger volumes in fronto-temporal and other cortical/subcortical regions compared with SZ, whereas SAD showed intermediate GM volumes. The two volumetric methodologies, VBM and FS, revealed highly overlapping results for cortical GM, but partially divergent results for subcortical volumes (basal ganglia, amygdala). Overall, these findings suggest that individuals across the psychosis dimension show both overlapping and unique GM phenotypes: decreased GM, predominantly in fronto-temporal regions, is characteristic of SZ but not of psychotic BD-P, whereas SAD display GM deficits overlapping with SZ, albeit less extensive. [Copyright &y& Elsevier]

Abstract: Objective: To examine the structural integrity of the dorsolateral prefrontal-basal ganglia–thalamocortical circuit in people with the deficit form of schizophrenia. Method: A three-dimensional structural MRI sequence was used to conduct morphometric assessments of cortical and subcortical regions in deficit and nondeficit outpatients with schizophrenia and healthy controls. Results: The superior prefrontal and superior and middle temporal gyral gray matter volumes were significantly smaller in the deficit versus the nondeficit group and normal control groups. There were no significant group differences in examined subcortical structures. Conclusion: People with deficit schizophrenia are characterized by selective reductions in the prefrontal and temporal cortex. [Copyright &y& Elsevier]

Abstract: Objectives: Cognitive rehabilitation can improve cognition in schizophrenia and prevent disability. It is unknown, however, whether a greater neurobiologic reserve, as measured by cortical volumes, will predict a favorable response to rehabilitation. We investigated this question in early course schizophrenia patients treated with Cognitive Enhancement Therapy (CET). Methods: Outpatients in the early course of schizophrenia or schizoaffective disorder were randomly assigned to CET (n=29) or an Enriched Supportive Therapy control (n=21) and treated for two years. Cortical surface area and gray matter volume data were collected before treatment using structural magnetic resonance imaging. Neurocognition and social cognition were assessed before, and after one and two years of treatment. Moderator analyses examined the impact of pre-treatment cortical surface area and gray matter volume on differential neurocognitive and social-cognitive response to CET. Results: Pre-treatment, whole brain cortical surface area and gray matter volume significantly moderated the effects of CET on social cognition, but not neurocognition. Greater neurobiologic reserve predicted a rapid social-cognitive response to CET in the first year of treatment; patients with less neurobiologic reserve achieved a comparable social-cognitive response by the second year. While nearly every regional measurement significantly contributed to this accelerated social-cognitive treatment response, effects were the strongest in the temporal cortex. Conclusions: A broad cortical surface area and gray matter reserve is associated with an accelerated social-cognitive response to CET in early schizophrenia, yet the benefits of cognitive rehabilitation are achieved in those with less initial cognitive resources after a longer duration of treatment. [Copyright &y& Elsevier]

Abstract: Background: Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis. Aims: We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non-psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures. Methods: Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within-subject factors and gender and study group as between-subject factors. Results: Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left–right/left + right  × 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness. Conclusions: Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Schizophrenia patients and their relatives show aberrant functional connectivity in default network regions (DRs) such as the medial prefrontal, lateral temporal, cingulate and inferior parietal cortices and executive regions such as the dorsolateral prefrontal cortex (DLPFC). Gray-matter volumetric alterations may be related to these functional connectivity deficits. Also, gray-matter volume inter-regional correlations may reflect altered inter-regional functional connectivity. Aims: To examine our prediction of alterations of gray-matter volumes and inter-regional volume correlations for DRs and the DLPFC in offspring of schizophrenia patients (OS). Methods: We assessed 64 adolescent and young adult OS and 80 healthy controls (HC) using T1-MRI. Regional gray-matter volumes and inter-regional volume correlations between the DRs and between the DLPFC and DRs on each side were compared across groups. Results: Compared to HC, OS had reductions in several DRs and the DLPFC after controlling age, gender, and intra-cranial volume, and correcting for multiple comparisons. OS had stronger (more positive) gray-matter volume inter-correlations between DRs and between DRs and the DLPFC. Conclusions: Volumetric deficits in the default network and in the DLPFC may be related to familial diathesis in schizophrenia and to functional connectivity abnormalities in those at familial risk. Increased inter-correlations between DRs and between DR and DLPFC gray-matter volumes may serve as surrogate indices of abnormal functional connectivity. [Copyright &y& Elsevier]

Abstract: Previous studies have suggested a relationship between frontal lobe-based neuropsychological functions and insight in schizophrenia. There is some evidence linking both smaller whole brain volume and frontal cortical atrophy to poor insight in this population. We investigated the relationship between total as well as specific prefrontal regional volumes and insight in schizophrenia. Twenty-eight stable outpatients with schizophrenia underwent magnetic resonance imaging scanning and assessment for insight. Insight was measured using the Birchwood self-report Insight Scale and the Expanded Schedule of Assessment of Insight. The whole brain and prefrontal regional (superior frontal, middle frontal, inferior frontal and orbitofrontal) volumes were then manually measured using the Cavalieri method and established criteria. Twenty healthy subjects were also scanned to provide control data for volumetric assessments. Smaller total prefrontal grey matter volume was moderately associated with a lower level of insight into the presence of illness. At the prefrontal sub-regional level, volumes of the superior, inferior and orbitofrontal regions contributed to this relationship, especially in males. It is concluded that smaller prefrontal grey matter volume is associated with poor insight into the presence of illness in stable schizophrenia patients. Future research should examine the association of specific dimensions of insight with frontal as well as non-frontal regional brain volumes. [Copyright &y& Elsevier]

Abstract: Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used “region of interest” (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322–331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem. [Copyright &y& Elsevier]

Abstract: The maturation of neocortical regions mediating social cognition during adolescence and young adulthood in relatives of schizophrenia patients may be vulnerable to heritable alterations of neurodevelopment. Prodromal psychotic symptoms, commonly emerging during this period in relatives, have been hypothesized to result from alterations in brain regions mediating social cognition. We hypothesized these regions to show longitudinal alterations and these alterations to predict prodromal symptoms in adolescent and young adult relatives of schizophrenia patients. 27 Healthy controls and 23 relatives were assessed at baseline and one-year follow-up using scale of prodromal symptoms and gray matter volumes of hypothesized regions from T1-MRI images. Regional volumes showing deficits on ANCOVA and repeated-measures ANCOVAs (controlling intra cranial volume, age and gender) were correlated with prodromal symptoms. At baseline, bilateral amygdalae, bilateral pars triangulares, left lateral orbitofrontal, right frontal pole, angular and supramarginal gyrii were smaller in relatives compared to controls. Relatives declined but controls increased or remained stable on bilateral lateral orbitofrontal, left rostral anterior cingulate, left medial prefrontal, right inferior frontal gyrus and left temporal pole volumes at follow-up relative to baseline. Smaller volumes predicted greater severity of prodromal symptoms at both cross-sectional assessments. Longitudinally, smaller baseline volumes predicted greater prodromal symptoms at follow-up; greater longitudinal decreases in volumes predicted worsening (increase) of prodromal symptoms over time. These preliminary findings suggest that abnormal longitudinal gray matter loss may occur in regions mediating social cognition and may convey risk for prodromal symptoms during adolescence and early adulthood in individuals with a familial diathesis for schizophrenia. [ABSTRACT FROM AUTHOR]