A Neuroanatomical Signature for Schizophrenia Across Different Ethnic Groups

Schizophrenia is a disabling clinical syndrome found across the world. While the incidence and clinical expression of this illness are strongly influenced by ethnic factors, it is unclear whether patients from different ethnicities show distinct brain deficits. In this multicentre study, we used structural Magnetic Resonance Imaging to investigate neuroanatomy in 126 patients with first episode schizophrenia who came from 4 ethnically distinct cohorts (White Caucasians, African-Caribbeans, Japanese, and Chinese). Each patient was individually matched with a healthy control of the same ethnicity, gender, and age (±1 year). We report a reduction in the gray matter volume of the right anterior insula in patients relative to controls (P < .05 corrected); this reduction was detected in all 4 ethnic groups despite differences in psychopathology, exposure to antipsychotic medication and image acquisition sequence. This finding provides evidence for a neuroanatomical signature of schizophrenia expressed above and beyond ethnic variations in incidence and clinical expression. In light of the existing literature, implicating the right anterior insula in bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety, we speculate that the neuroanatomical deficit reported here may represent a transdiagnostic feature of Axis I disorders.Key words: schizophrenia, neuroanatomy, ethnicity, magnetic resonance imaging, voxel-based morphometrySchizophrenia is common, severely disabling, and has major socioeconomic impact. Consistent with the current understanding of illness as a collection of heterogeneous clinical syndromes,^1,2 epidemiological studies have found that the incidence and clinical expression of schizophrenia vary according to a number of sociodemographic factors including, amongst others, the ethnic origin of the patients under investigation.^3–7 For example, patients from Asian ethnicities are more likely to experience visual hallucinations, whereas patients from western cultures and Caucasian ethnicities are more likely to suffer from auditory hallucinations.⁵ In addition, the content of hallucination and delusions is also strongly influenced by the patient’s ethnic milieus.⁵ Even within the same geographical area, ethnic origin has been found to strongly influence the incidence and manifestation of the disease. For example, African-Caribbeans living in London are more likely to develop schizophrenia⁶ and suffer from affective symptoms⁷ than White Caucasians from the same neighbourhood. Likewise, Mâori people in New Zealand are more likely to present with hallucinations and aggression and less likely to present with depression and self-harm than non-Mâori people from the same area.⁸Over the past 2 decades, neuroimaging techniques have enabled greater understanding of the neuroanatomical basis of this illness.^9–14 So far, however, the impact of ethnic characteristics on the neuroanatomical basis of schizophrenia has received minimal attention in the existing literature.¹⁵ Some neuroimaging studies have recruited ethnically uniform cohorts in order to minimize individual variation within each experimental group^16,17; whereas other studies have included participants from a range of ethnic backgrounds based on the assumption that this would not have a significant impact on the results.^10,18 Thus, at present, we know very little about whether patients from different ethnicities are characterised by similar or different neuroanatomical deficits. Here, we addressed this question by investigating 4 ethnically distinct samples comprising of (1) White Caucasian, (2) African-Caribbean, (3) Japanese, and (4) Chinese participants. The 4 groups were uniform with respect to the stage of the illness, as all patients had experienced a first episode of schizophrenia within the previous 24 months. In addition, in all 4 groups, each patient was individually matched with a healthy control of the same ethnicity, gender, and age (±1 year) in order to minimize the potential impact of these demographic variables. As the 4 groups were scanned at different sites using different scanners and acquisition sequences (see supplementary table S1 for detail), any discrepancy between datasets could be due to methodological differences. For the purpose of the present investigation, therefore, we focussed on differences between patients and controls that were expressed consistently across the 4 groups. As we preprocessed and analysed each dataset independently, using ethnic-specific templates, our investigation can be thought of as a series of replication studies across 4 independent datasets. We hypothesised that the 4 groups would show consistent neuroanatomical reductions in specific prefrontal, parietal, and limbic regions that are implicated in existing animal¹⁹ and human^11,20–24 models of schizophrenia. This would provide evidence for a neuroanatomical signature of schizophrenia expressed above and beyond ethnic differences in incidence and clinical expression.