Shared and distinct white matter abnormalities in adolescent-onset schizophrenia and adolescent-onset psychotic bipolar disorder.

Background: While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.

Methods: Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments.

Comparison of Surface Area and Cortical Thickness Asymmetry in the Human and Chimpanzee Brain.

Comparative study of the structural asymmetry of the human and chimpanzee brain may shed light on the evolution of language and other cognitive abilities in humans. Here we report the results of vertex-wise and ROI-based analyses that compared surface area (SA) and cortical thickness (CT) asymmetries in 3D MR images obtained for 91 humans and 77 chimpanzees. The human brain is substantially more asymmetric than the chimpanzee brain.

Automatic analysis of cross-sectional cerebral asymmetry on 3D in vivo MRI scans of human and chimpanzee.

One prominent feature of human brain asymmetry is the cerebral torque. To investigate whether this characteristic is shared with chimpanzees who are our closest extant relative, we developed an automatic method to compute cerebral hemisphere width and perimeter length on consecutive 2D sections through 3D MR images obtained in vivo for 91 human and 78 chimpanzee brains. In brief, contiguous inter-hemispheric width and perimeter asymmetries were calculated on coronal sections, which in profile allow us to examine asymmetry in relation to speciation.

Cerebral torque is human specific and unrelated to brain size.

The term "cerebral torque" refers to opposing right-left asymmetries of frontal and parieto-occipital regions. These are assumed to derive from a lateralized gradient of embryological development of the human brain. To establish the timing of its evolution, we computed and compared the torque, in terms of three principal features, namely petalia, shift, and bending of the inter-hemispheric fissure as well as the inter-hemispheric asymmetry of brain length, height and width for in vivo Magnetic Resonance Imaging (MRI) scans of 91 human and 78 chimpanzee brains.

Measurement of Sylvian Fissure asymmetry and occipital bending in humans and Pan troglodytes.

The evolution of human-specific lateralised functions such as language has been linked to the development of structural asymmetries in the brain. Here we applied state of the art image analysis techniques to measure Sylvian Fissure (SF) asymmetry and Occipital Bending (OB) in 3D Magnetic Resonance (MR) images of the brain obtained in-vivo for 30 humans and 30 chimpanzees (Pan troglodytes). SF morphology differed between species, with the human SF terminating more superiorly in right inferior parietal lobe, an asymmetry that was on average absent in chimpanzees (F (1,52) = 5.

Patients with chronic bipolar disorder exhibit widespread increases in extracellular free water.

Objectives: Bipolar disorder (BP) is a debilitating psychiatric disease that is not well understood. Previous diffusion magnetic resonance imaging (dMRI) studies of BP patients found prominent microstructural white matter (WM) abnormalities of reduced fractional anisotropy (FA). Because FA is a nonspecific measure, relating these abnormalities to a specific pathology is difficult.

Human torque is not present in chimpanzee brain.

We searched for positional brain surface asymmetries measured as displacements between corresponding vertex pairs in relation to a mid-sagittal plane in Magnetic Resonance (MR) images of the brains of 223 humans and 70 chimpanzees. In humans deviations from symmetry were observed: 1) a Torque pattern comprising right-frontal and left-occipital "petalia" together with downward and rightward "bending" of the occipital extremity, 2) leftward displacement of the anterior temporal lobe and the anterior and central segments of superior temporal sulcus (STS), and 3) posteriorly in the position of left occipito-temporal surface accompanied by a clockwise rotation of the left Sylvian Fissure around the left-right axis. None of these asymmetries was detected in the chimpanzee, nor was associated with a sex difference.

The XY gene hypothesis of psychosis: origins and current status.

Sex differences in psychosis and their interaction with laterality (systematic departures from 50:50 left-right symmetry across the antero-posterior neural axis) are reviewed in the context of the X-Y gene hypothesis. Aspects of laterality (handedness/cerebral asymmetry/the torque) predict (1) verbal and non-verbal ability in childhood and across adult life and (2) anatomical, physiological, and linguistic variation relating to psychosis. Neuropsychological and MRI evidence from individuals with sex chromosome aneuploidies indicates that laterality is associated with an X-Y homologous gene pair.

Laterality interacts with sex across the schizophrenia/bipolarity continuum: an interpretation of meta-analyses of structural MRI.

Review of the first comprehensive meta-analysis of VBM (voxel-based morphometry) studies in schizophrenia indicates asymmetrical reductions of anterior cingulate gyrus to the right, and medial temporal lobe (including the uncus) and para-hippocampal gyrus to the left. In subsequent meta-analyses of schizophrenia and bipolar disorder change in these limbic structures is systematically related to change in the insula. Deficits in insula (and para-hippocampal gyrus) to the left, and dorsal anterior cingulate gyrus to the right are greater in schizophrenic psychoses whereas deficits in anterior cingulate to the left and insula to the right are greater in bipolar illness.

The protocadherin 11X/Y (PCDH11X/Y) gene pair as determinant of cerebral asymmetry in modern Homo sapiens.

Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single "right-shift" gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X-Y homologous region of the sex chromosomes. The Xq21.

Hemispheric asymmetry in the fusiform gyrus distinguishes Homo sapiens from chimpanzees.

While the neural basis for linguistic communication has been linked to brain structural asymmetries found only in humans (wider connective spacing is found between the minicolumns of neurons in the left hemisphere language areas), it is unknown if the opposite microanatomical asymmetry exists in the fusiform gyrus which typically supports a right hemisphere bias for face processing. Unlike language, face processing is an ability shared with chimpanzees and, as Darwin observed, the widespread use of facial expressions in animal communication suggests a biological basis. We tested the principle that minicolumn asymmetry follows typical functional dominance in humans, and tested its evolutionary continuity, by measuring minicolumn width, neuronal size and density in the mid-fusiform cortex in 14 humans and 14 chimpanzees.

Paracingulate sulcus asymmetry; sex difference, correlation with semantic fluency and change over time in adolescent onset psychosis.

The left paracingulate sulcus (PCS) is longer than the right and the adjacent cortex is activated by the generation of words. In adult patients with chronic schizophrenia the anatomical asymmetry is reduced. In 35 controls and 38 adolescents with schizophrenia or schizoaffective disorder (mean age = 16 years) we found that semantic verbal fluency correlated with leftward PCS asymmetry in controls but not in patients.

Neuropathology of epilepsy and psychosis: the contributions of J.A.N. Corsellis.

Professor J.A.N.

Asymmetry loss is local rather than global in adolescent onset schizophrenia.

Meta-analyses in adult-onset schizophrenia report loss of normal planum temporale (PT) asymmetry, posited to relate to language and symptoms, but are inconclusive regarding global "cerebral torque". PT asymmetry has been reported unchanged in childhood onset schizophrenia. Here the discrepancy is examined in adolescence.

Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk.

Background: The nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear.

Aims: To re-examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year.

Method: Symptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n = 101) were re-analysed in the context of duration of untreated illness (DUI).

Attenuated asymmetry of functional connectivity in schizophrenia: a high-resolution EEG study.

The interhemispheric asymmetries that originate from connectivity-related structuring of the cortex are compromised in schizophrenia (SZ). Under the assumption that such abnormalities affect functional connectivity, we analyzed its correlate-EEG synchronization-in SZ patients and matched controls. We applied multivariate synchronization measures based on Laplacian EEG and tuned to various spatial scales.

Microduplications of 16p11.2 are associated with schizophrenia.

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.

Schizophrenia delays and alters maturation of the brain in adolescence.

Early-onset schizophrenia appears to be clinically more severe than the adult-onset form of the disease. In a previous study, we showed that anatomically related grey and white matter abnormalities found in adolescents patients were larger and more widespread than what had been reported in the literature on adult schizophrenia. Particularly, we found novel structural abnormalities in the primary sensorimotor and premotor systems.

Dichotic listening impairments in early onset schizophrenia are associated with reduced left temporal lobe volume.

Dichotic listening (DL) impairments, in particular the loss or reduction of right ear advantage (REA) in people with schizophrenia have been variously interpreted as both a state and trait marker for schizophrenia. To date, there has been no comprehensive investigation of dichotic language impairments in relation to the structural integrity of the temporal cortex--the likely neural substrate for such impairments. In this study of 39 early onset patients and matched controls we used a dichotic listening procedure and examined the findings in relation to MRI measurements of gross and regional cerebral volumes.