• Comparison of regional brain deficit patterns in common psychiatric and neurological disorders as revealed by big data

      Kochunov, Peter; Ryan, Meghann C.; Yang, Qifan; Hatch, Kathryn S.; Zhu, Alyssa; Thomopoulos, Sophia I.; Jahanshad, Neda; Schmaal, Lianne; Thompson, Paul M.; Chen, Shuo; et al. (Elsevier Inc., 2021-01-26)
      Neurological and psychiatric illnesses are associated with regional brain deficit patterns that bear unique signatures and capture illness-specific characteristics. The Regional Vulnerability Index (RVI) was developed to quantify brain similarity by comparing individual white matter microstructure, cortical gray matter thickness and subcortical gray matter structural volume measures with neuroanatomical deficit patterns derived from large-scale meta-analytic studies. We tested the specificity of the RVI approach for major depressive disorder (MDD) and Alzheimer's disease (AD) in a large epidemiological sample of UK Biobank (UKBB) participants (N = 19,393; 9138 M/10,255F; age = 64.8 ± 7.4 years). Compared to controls free of neuropsychiatric disorders, participants with MDD (N = 2,248; 805 M/1443F; age = 63.4 ± 7.4) had significantly higher RVI-MDD values (t = 5.6, p = 1·10−8), but showed no detectable difference in RVI-AD (t = 2.0, p = 0.10). Subjects with dementia (N = 7; 4 M/3F; age = 68.6 ± 8.6 years) showed significant elevation in RVI-AD (t = 4.2, p = 3·10−5) but not RVI-MDD (t = 2.1, p = 0.10) compared to controls. Even within affective illnesses, participants with bipolar disorder (N = 54) and anxiety disorder (N = 773) showed no significant elevation in whole-brain RVI-MDD. Participants with Parkinson's disease (N = 37) showed elevation in RVI-AD (t = 2.4, p = 0.01) while subjects with stroke (N = 247) showed no such elevation (t = 1.1, p = 0.3). In summary, we demonstrated elevation in RVI-MDD and RVI-AD measures in the respective illnesses with strong replicability that is relatively specific to the respective diagnoses. These neuroanatomic deviation patterns offer a useful biomarker for population-wide assessments of similarity to neuropsychiatric illnesses.
    • Thinking about hallucinations: why philosophy matters.

      Wilkinson, Sam; Green, Huw; Hare, Stephanie; Houlders, Joseph; Humpston, Clara; Alderson-Day, Benjamin (Taylor and Francis Inc., 2021-12-07)
      Introduction: Hallucinations research is increasingly incorporating philosophy or the work of philosophically trained individuals. We present three different ways in which this is successfully implemented to the enhancement of knowledge and understanding of hallucinations and related phenomena. Method: We review contributions from phenomenology, philosophy of cognitive science, and philosophy of science and psychiatry. Results: We demonstrate that these areas of philosophy make significant contributions to hallucinations research. Phenomenology gives us a sophisticated and critical understanding of the lived experience of hallucinations. Philosophy of cognitive science enables big-picture theorising and synthesis of ideas, as well as a critical engagement with new paradigms. Philosophy of science and psychiatry raises valuable and theoretically informed questions about diagnosis and categorisation. Conclusions: These contributions reflect both the methodological variety within philosophy and its relevance to the hallucinations researcher. © 2021 The Author(s).
    • A White Matter Connection of Schizophrenia and Alzheimer's Disease

      Kochunov, Peter; Zavaliangos-Petropulu, Artemis; Jahanshad, Neda; Thompson, Paul M; Ryan, Meghann C; Chiappelli, Joshua; Chen, Shuo; Du, Xiaoming; Hatch, Kathryn; Adhikari, Bhim; et al. (Oxford University Press, 2020-07-18)
      Schizophrenia (SZ) is a severe psychiatric illness associated with an elevated risk for developing Alzheimer's disease (AD). Both SZ and AD have white matter abnormalities and cognitive deficits as core disease features. We hypothesized that aging in SZ patients may be associated with the development of cerebral white matter deficit patterns similar to those observed in AD. We identified and replicated aging-related increases in the similarity between white matter deficit patterns in patients with SZ and AD. The white matter "regional vulnerability index" (RVI) for AD was significantly higher in SZ patients compared with healthy controls in both the independent discovery (Cohen's d = 0.44, P = 1·10-5, N = 173 patients/230 control) and replication (Cohen's d = 0.78, P = 9·10-7, N = 122 patients/64 controls) samples. The degree of overlap with the AD deficit pattern was significantly correlated with age in patients (r = .21 and .29, P < .01 in discovery and replication cohorts, respectively) but not in controls. Elevated RVI-AD was significantly associated with cognitive measures in both SZ and AD. Disease and cognitive specificities were also tested in patients with mild cognitive impairment and showed intermediate overlap. SZ and AD have diverse etiologies and clinical courses; our findings suggest that white matter deficits may represent a key intersecting point for these 2 otherwise distinct diseases. Identifying mechanisms underlying this white matter deficit pattern may yield preventative and treatment targets for cognitive deficits in both SZ and AD patients.