Regional updateElucidation of shared and specific white matter findings underlying psychopathology clusters in schizophrenia
Introduction
The dysconnection hypothesis indicates that schizophrenia is a disorder of brain connectivity (Friston and Frith, 1995). Previous diffusion tensor imaging (DTI) studies have found reductions of fractional anisotropy (FA) in different brain regions involving the frontal, temporal, limbic, parietal and occipital regions in patients with schizophrenia (d’Albis and Houenou, 2015, Peters et al., 2010). Considering the diversity in clinical presentations related to schizophrenia, it would be clinically meaningful to determine white matter findings underlying different symptom clusters (Karlsgodt, 2016).
The Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987), a common rating tool to assess the nature and level of psychopathology in schizophrenia, was originally designed with three subscales i.e. positive, negative and general psychopathology, and recent factor analyses have generally found five-factor models consisting of Positive, Negative, Disorganised, Depression/Emotional Distress and Excitement/Mania factors (Jiang et al., 2013, van der Gaag et al., 2006, Wallwork et al., 2012). However, the lack of a consistent, consensus five-factor model suggests that a locally and contextually derived model might be more appropriate.
Overall, studies examining the relationship between brain white matter integrity and PANSS factors were limited and most studies have focused mainly on positive and negative symptom subscales and not the full factors. Positive symptoms were associated with increased or decreased FA in different WM structures, particularly in genu of corpus callosum (gCC) and superior longitudinal fasciculus (SLF) (Caprihan et al., 2015, Mitelman et al., 2007). This might be due to different sample sizes as increased FA was usually found in studies with smaller number of subjects (Park et al., 2014, Rotarska-Jagiela et al., 2009). In addition, higher negative symptoms were associated with decreased FA in gCC, inferior fronto-occipital fasciculus (IFOF) and inferior longitudinal fasciculus (ILF) (Arnedo et al., 2015, Sun et al., 2015).
Thus in this study, we sought to examine the patterns of WM anomalies associated with symptom clusters as measured by PANSS amongst our patients with schizophrenia.
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Participants
Out of 244 participants, 96 were healthy controls (HC) and 148 were participants with schizophrenia (SZ). HC were recruited from the community via advertisements and patients with SZ were recruited from the Institute of Mental Health, Singapore. For all participants, presence and absence of psychopathology was established by a board-certificated psychiatrist (K.S.) using information obtained from the clinical history, mental status examination, existing medical records, interviews with
Study sample
Differences between HC and SZ groups were examined (Table 1). Compared with HC, SZ were more likely to be single and had fewer years of education.
For FA, significant main and interaction effects were found (See Supplementary Figures). The SZ group had decreased FA for gCC, bilateral CG and bilateral SLF (Group effect). Those who were older also had decreased FA for left SS, right CG, and right CHIP (Age effect). Post-hoc analyses found that within the control group, as age increased, FA
Discussion
Given the heterogeneity of WM findings in schizophrenia, this study evaluated the use of psychotic psychopathology clusters to clarify WM findings underlying these clinical presentations. A three-factor EFA-derived model, consisting of Positive, Negative and Disorganised factors, was the best fit for the PANSS data. Decreased FA in both gCC and bilateral CG were associated with all three symptom clusters. Higher Negative factor scores were also uniquely associated with decreased FA in right SS
Conflict of interest
Nil.
Funding
This study was supported by the National Healthcare Group Research Grant (NHG-SIG/05004) and Singapore Bioimaging Consortium Research Grant (SBIC RP C-009/2006) awarded to KS.
Contributors
K Sim designed the study and wrote the protocol. J Lim managed the literature searches, undertook statistical analysis and wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Acknowledgements
The authors thank all the subjects, their families and the staff for their support of this study.
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