Review article Laterality interacts with sex across the schizophrenia/bipolarity continuum: An interpretation of meta-analyses of structural MRI Timothy J. Crow a,n , Steven A. Chance a , Thomas H. Priddle a , Joaquim Radua b,c , Anthony C. James d a SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK b King's College London, Institute of Psychiatry, Department of Psychosis Studies, London SE5 8AF, UK c FIDMAG – CIBERSAM Research Unit, Sant Boi de Llobregat, Barcelona, Spain d Highfield Adolescent Unit, Warneford Hospital, Oxford OX3 7JX, UK article info Article history: Received 28 August 2011 Received in revised form 29 June 2013 Accepted 31 July 2013 Keywords: Meta-analysis Torque MRI Speciation Sapiens Language Continuum abstract 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. Thus (1) brain structures implicated in schizophrenia include those implicated in bipolar disorder, (2) the variation that separates the prototypical psychoses may be a subset of that relating to the structural asymmetry (the “torque”) characteristic of the human brain, and (3) the meta-analysis of Bora et al. (2012) indicates that laterality of involvement of the insula and cingulate gyrus across the spectrum of bipolar and schizophrenic psychoses is critically dependent upon the sex ratio. Thus structural change underlying the continuum of psychosis relates to the interaction of laterality and sex. & 2013 Elsevier Ireland Ltd. All rights reserved. Contents 1. Background .......................................................................................................... 2 1.1. All meta-analyses of VBM studies (2005–2012) in schizophrenia and bipolar disorder ........................................ 2 1.2. Laterality in Honea et al. (2005) .................................................................................... 2 1.3. Meta-analyses (2005–2011) using ALE or SDM ........................................................................ 3 1.4. Formal tests of deviations from symmetry............................................................................ 3 1.5. Anatomical profile of schizophrenia ................................................................................. 5 1.6. Size of the insula deficit .......................................................................................... 5 1.7. Anatomical profile of bipolar disorder ............................................................................... 7 1.8. Hemisphere by sex interactions .................................................................................... 7 2. Discussion ........................................................................................................... 7 2.1. Anatomy of psychosis ............................................................................................ 7 2.2. The significance of sex differences .................................................................................. 8 2.3. The limbic concept of psychosis .................................................................................... 9 2.4. Anatomy of asymmetry ........................................................................................... 9 2.5. Implications for the genetics of psychosis ........................................................................... 10 3. Conclusion .......................................................................................................... 10 Contributions............................................................................................................ 10 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/psychres Psychiatry Research 0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.07.043 n Corresponding author. Tel.: +44 1865 455917; fax: +44 1865 455922. E-mail address: tim.crow@psych.ox.ac.uk (T.J. Crow) Please cite this article as: Crow, T.J., et al., Laterality interacts with sex across the schizophrenia/bipolarity continuum: An interpretation of meta-analyses of structural MRI. Psychiatry Research (2013), http://dx.doi.org/10.1016/j.psychres.2013.07.043i Psychiatry Research ∎ (∎∎∎∎) ∎∎∎–∎∎∎