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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.
Blokland, GAM, Grove, J, Chen, CY, Cotsapas, C, Tobet, S, Handa, R, , , St Clair, D, Lencz, T, Mowry, BJ, et al
Biological psychiatry. 2022;(1):102-117
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Abstract
BACKGROUND Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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Stress and support for parents of youth with bipolar disorder.
Nadkarni, RB, Fristad, MA
The Israel journal of psychiatry and related sciences. 2012;(2):104-10
Abstract
BACKGROUND This article reviews stress related to parenting a youth with bipolar disorder (BD), maladaptive coping, immunologic and physical functioning related to chronic stress; presents preliminary findings about the association between immune parameters and health conditions, mental health indices and interpersonal functioning in parents of children with mood disorders; and provides recommendations for stress management based on clinical trials of family-based psychoeducational psychotherapy (PEP). DATA Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), Epstein Barr Virus (EBV), nutritional markers and measures of physical health, mental health and interpersonal functioning were collected from 26 parents of mood disordered children. Higher CRP was associated with more perceived stress, more depression, increased incidence of illness/ physical conditions, and lower albumin levels. Elevated IL-6 was associated with higher nicotine use. LIMITATIONS Sample size and demographics were restricted, limiting generalizability. CONCLUSION Pilot data are consistent with literature from adult caregivers, and suggest caregivers who are more stressed also evidence some signs of immune abnormality. Evidence-based strategies to support parents are discussed.