Complex psychiatry最新文献

Schizophrenia (SZ) is a common and debilitating psychiatric disorder with limited effective treatment options. Although highly heritable, risk for this polygenic disorder depends on the complex interplay of hundreds of common and rare variants. Translating the growing list of genetic loci significantly associated with disease into medically actionable information remains an important challenge. Thus, establishing platforms with which to validate the impact of risk variants in cell-type-specific and donor-dependent contexts is critical. Towards this, we selected and characterized a collection of 12 human induced pluripotent stem cell (hiPSC) lines derived from control donors with extremely low and high SZ polygenic risk scores (PRS). These hiPSC lines are publicly available at the California Institute for Regenerative Medicine (CIRM). The suitability of these extreme PRS hiPSCs for CRISPR-based isogenic comparisons of neurons and glia was evaluated across 3 independent laboratories, identifying 9 out of 12 meeting our criteria. We report a standardized resource of publicly available hiPSCs on which we hope to perform genome engineering and generate diverse kinds of functional data, with comparisons across studies facilitated by the use of a common set of genetic backgrounds.

Major depressive disorder (MDD) affects more than cognition, having a temporal relationship with neuroinflammatory pathways of Parkinson's disease (PD). Although this association is supported by epidemiological and clinical studies, the underlying mechanisms are unclear. Microglia and astrocytes play crucial roles in the pathophysiology of both MDD and PD. In PD, these cells can be activated by misfolded forms of the protein α-synuclein to release cytokines that can interact with multiple different physiological processes to produce depressive symptoms, including monoamine transport and availability, the hypothalamus-pituitary axis, and neurogenesis. In MDD, glial cell activation can be induced by peripheral inflammatory agents that cross the blood-brain barrier and/or c-Fos signalling from neurons. The resulting neuroinflammation can cause neurodegeneration due to oxidative stress and glutamate excitotoxicity, contributing to PD pathology. Astrocytes are another major link due to their recognized role in the glymphatic clearance mechanism. Research suggesting that MDD causes astrocytic destruction or structural atrophy highlights the possibility that accumulation of α-synuclein in the brain is facilitated as the brain cannot adequately clear the protein aggregates. This review examines research into the overlapping pathophysiology of MDD and PD with particular focus on the roles of glial cells and neuroinflammation.

The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a polydiagnostic instrument for substance use and psychiatric disorders. We translated the SSADDA English version into Chinese (SSADDA-Chinese) and report here our examination of the diagnostic reliability and validity of DSM-IV substance dependence (SD) diagnoses in a Mandarin-speaking sample in Taiwan. We recruited 125 subjects who underwent an assessment of lifetime SD diagnoses using both the SSADDA-Chinese and the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-Chinese). Thirty-one subjects were retested with the SSADDA-Chinese. Cohen's κ statistic, which measures chance-corrected agreement, was used to measure the test-retest reliability and concurrent validity of the individual SD diagnoses. There was a high degree of concordance between SD diagnoses made using the SSADDA-Chinese and the SCID-Chinese, including those for dependence on alcohol (κ = 0.83), ketamine (κ = 0.97), methamphetamine (κ = 0.93), and opioids (κ = 0.95). The test-retest reliability of dependence diagnoses for ketamine (κ = 0.95), methamphetamine (κ = 0.80), and opioids (κ = 1.00) obtained using the SSADDA-Chinese was excellent, while that for alcohol dependence (κ = 0.63) and nicotine dependence (κ = 0.65) was good. We conclude that the SSADDA-Chinese is a reliable and valid instrument for the diagnosis of major SD traits in Mandarin-speaking populations.

Introduction: Accumulating evidence suggests a relationship between the immune system, neuroinflammation, and mood disorders such as bipolar disorder (BD). However, the immunological landscape of critical brain structures implicated with BD, such as the dorsal striatum, has yet to be characterized. This study sought to investigate the immunological composition of dorsal striata in patients with BD.

Methods: CIBERSORTx, an established RNA deconvolution algorithm, was applied on RNA-sequencing data developed from dorsal striata of 18 BD patients and 17 controls. A validated gene signature matrix for 22 human hematopoietic cell subsets was used to infer the relative proportions of immune cells that were present in the original brain tissue.

Results: Deconvolution of the bulk gene expression data showed that dorsal striata from BD subjects had a significantly greater relative abundance of monocytes compared to control samples.

Conclusion: Monocytes may play a role in the pathogenesis of BD in dorsal striata. Further studies are warranted to confirm the computational results presented herein.