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. 2021 Jul:27-28:10.1016/j.pmip.2021.100078.
doi: 10.1016/j.pmip.2021.100078.

Cooperative Studies Program (CSP) #572: A Study of Serious Mental Illness in Veterans as a Pathway to personalized medicine in Schizophrenia and Bipolar Illness

Philip D Harvey  1   2 , Tim B Bigdeli  3   4 , Ayman H Fanous  3   4 , Yuli Li  5   6 , Nallakkandi Rajeevan  5   6 , Frederick Sayward  5   6 , Krishnan Radhakrishnan  5   7   8 , Grant Huang  9 , Mihaela Aslan  3   4
Affiliations

Cooperative Studies Program (CSP) #572: A Study of Serious Mental Illness in Veterans as a Pathway to personalized medicine in Schizophrenia and Bipolar Illness

Philip D Harvey et al. Pers Med Psychiatry. 2021 Jul.

Abstract

Background: Personalization of psychiatric treatment includes treatment of symptoms, cognition and functional deficits, suicide, and medical co-morbidities. VA Collaborative Study 572 examined a large sample of male and female veterans with schizophrenia (n=3,942) and with bipolar disorder (n=5,414) with phenotyping and genomic analyses. We present the results to date and future directions.

Methods: All veterans received a structured diagnostic interview and assessments of suicidal ideation and behavior, PTSD, and health. Veterans with schizophrenia were assessed for negative symptoms and lifetime depression. All were assessed with a cognitive and functional capacity assessment. Data for genome wide association studies were collected. Controls came from the VA Million Veteran Program.

Results: Suicidal ideation or behavior was present in 66%. Cognitive and functional deficits were consistent with previous studies. 40% of the veterans with schizophrenia had a lifetime major depressive episode and PTSD was present in over 30%. Polygenic risk score (PRS) analyses indicated that cognitive and functional deficits overlapped with PRS for cognition, education, and intelligence in the general population and PRS for suicidal ideation and behavior correlated with previous PRS for depression and suicidal ideation and behavior, as did the PRS for PTSD.

Discussion: Results to date provide directions for personalization of treatment in SMI, veterans with SMI, and veterans in general. The results of the genomic analyses suggest that cognitive deficits in SMI may be associated with general population features. Upcoming genomic analyses will reexamine the issues above, as well as genomic factors associated with smoking, substance abuse, negative symptoms, and treatment response.

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Figures

Figure 1.
Figure 1.
Schematic of the VHA Data Warehousing Infrastructure
Figure 2:
Figure 2:
Association of PRS with SCID- and EHR-based SCZ diagnoses. We constructed PRS using summary statistics from the Psychiatric Genomic Consortium (PGC), Genomic Psychiatric Cohort (GPC), and a recent East Asian meta-analysis. For varying P-value thresholds, the variance explained is reported in terms of R2 on the liability scale (K=0.01). Training datasets are listed in order of discovery N (e.g., PGC-SCZ3 is largest). Dotted lines display AFR results rescaled to fit the plotting area. NB: We included CSP #572 participants with confirmed SCZ diagnoses in all analyses.
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