Are Bipolar Disorder and Schizophrenia Neuroanatomically Distinct? An Anatomical Likelihood Meta-analysis

Abstract

Objective: There is renewed debate on whether modern diagnostic classification should adopt a dichotomous or dimensional approach to schizophrenia and bipolar disorder. This study synthesizes data from voxel-based studies of schizophrenia and bipolar disorder to estimate the extent to which these conditions have a common neuroanatomical phenotype. Methods: A post-hoc meta-analytic estimation of the extent to which bipolar disorder, schizophrenia, or both conditions contribute to brain gray matter differences compared to controls was achieved using a novel application of the conventional anatomical likelihood estimation (ALE) method. 19 schizophrenia studies (651 patients and 693 controls) were matched as closely as possible to 19 bipolar studies (540 patients and 745 controls). Result: Substantial overlaps in the regions affected by schizophrenia and bipolar disorder included regions in prefrontal cortex, thalamus, left caudate, left medial temporal lobe, and right insula. Bipolar disorder and schizophrenia jointly contributed to clusters in the right hemisphere, but schizophrenia was almost exclusively associated with additional gray matter deficits (left insula and amygdala) in the left hemisphere. Limitation: The current meta-analytic method has a number of constraints. Importantly, only studies identifying differences between controls and patient groups could be included in this analysis. Conclusion: Bipolar disorder shares many of the same brain regions as schizophrenia. However, relative to neurotypical controls, lower gray matter volume in schizophrenia is more extensive and includes the amygdala. This fresh application of ALE accommodates multiple studies in a relatively unbiased comparison. Common biological mechanisms may explain the neuroanatomical overlap between these major disorders, but explaining why brain differences are more extensive in schizophrenia remains challenging.

A combined VBM and DTI study of schizophrenia: bilateral decreased insula volume and cerebral white matter disintegrity corresponding to subinsular white matter projections unlinked to clinical symptomatology

“…Studies with larger samples showed that depression w associated with bilaterally decreased insula volumes (16). In our study, insula volume was found decreased bilaterally in patients with schizophrenia compared with normal controls, consistent with other reports (2,17,18). Decreased insula volumes were reported even in first episode schizophrenia cases (19)(20)(21).…”

Is there an anatomical endophenotype for neurodevelopmental disorders? A review of dual disorder anatomical likelihood estimation (ALE) meta-analyses of grey matter volumes

“…However, it should be acknowledged that autism is not a single disorder but a spectrum with wide phenotypic expression [50]. Indeed we have previously suggested that, on the spectrum of complex neurodevelopmental disorders, which includes autism, schizophrenia and Asperger's syndrome, our results indicate changes to brain anatomy in Asperger's syndrome may be closer to schizophrenia [21]. This is not a new idea -many years ago Wolff described children with a diagnosis of schizoid personality disorder as phenotypically akin to the eponymous syndrome described by Asperger [51].…”

“…This permitted extraction of the percentage contribution made by studies of schizophrenia or bipolar disorder to the overall result. The pipeline for this modified ALE is shown in Figure 1, taken from our original publication [21].…”

“…Thus the "overlap" could have been, at least partly, a false positive, given the few data points from bipolar studies might have coincided by chance with some part of the extensive schizophrenia map. To address this issue we designed a "dual disorder" ALE study in which VBM studies of bipolar disorder were matched 1:1 to schizophrenia studies on variables such as duration of illness and medication exposure [21]. In addition we modified the ALE kernal to generate a joint map of brain regions affected by schizophrenia and bipolar disorder.…”

Neuroanatomical voxel-based profile of schizophrenia and bipolar disorder

“…A large number of region-based and voxel-based approaches has already been applied to identify the structural abnormalities associated with SCZ and BD (Arnone et al 2009;Ellison-Wright & Bullmore, 2010;Yu et al 2010;Bora et al 2012;Selvaraj et al 2012). Whole-brain voxel-based morphometry (VBM) studies highlighted overlapping areas of grey matter (GM) reduction in SCZ and BD compared with HC, mainly located in bilateral insula and anterior cingulate cortex.…”