Susceptibility Genes Are Enriched in Those of the HSV-1/host Interactome in Psychiatric and Neurological Disorders.

Susceptibility genes are enriched in those of the HSV-1/host interactome in psychiatric and neurological disorders.

Pathog Dis. 2013 Aug 3;
Carter CJ

Herpes simplex (HSV-1) can promote beta-amyloid deposition and tau phosphorylation, demyelination or cognitive deficits relevant to Alzheimer’s disease or multiple sclerosis and to many neuropsychiatric disorders with which it has been implicated. A seroprevalence much higher than disease incidence has called into question any primary causal role. However, as also the case with risk promoting polymorphisms, (also present in control populations) any causal effects are likely to be conditional. During its life cycle, the virus binds to many proteins and modifies the expression of multiple genes creating a host/pathogen interactome involving 1347 host genes. This dataset is heavily enriched in the susceptibility genes for multiple sclerosis (P= 1.3E-99) >Alzheimer’s disease > schizophrenia > Parkinsonism > depression> bipolar disorder> childhood obesity> chronic fatigue> autism > and anorexia (P=0.047) but not ADHD, a relationship maintained for GWAS datasets in multiple sclerosis and Alzheimer’s disease. Overlapping susceptibility gene/interactome datasets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies. In this way, the same pathogen could contribute to multiple diseases in a gene-dependent manner and condition the risk promoting effects of the genes whose function it disrupts. This article is protected by copyright. All rights reserved. HubMed – depression

Adolescents and young adults with down syndrome presenting to a medical clinic with depression: Co-morbid obstructive sleep apnea.

Am J Med Genet A. 2013 Aug 2;
Capone GT, Aidikoff JM, Taylor K, Rykiel N

Adolescents and young adults with Down syndrome (DS) sometimes experience new-onset mood disorder and decline in adaptive skills. The clinical phenomenon is poorly characterized and its pathogenesis is not understood. The possible contribution of obstructive sleep apnea syndrome (OSAS) to this phenomenon has not been studied. Subjects were ascertained as a convenience sample through our clinic for persons with DS and medical or mental health concerns between 2004 and 2009. When mood symptoms were present an axis I diagnosis was made using DSM-IV-R criteria. Subjects without an axis I diagnosis served as controls. The Reiss scales for children’s dual diagnosis and the aberrant behavior checklist (ABC) were completed by caretakers. Twenty-eight cases meeting criteria for major depressive episode (MDE) and nine controls without psychopathology were referred for overnight polysomnography (PSG). Functional decline was reported in 19 (68%) of cases with MDE, but none of the controls. Twenty-four (86%) cases had OSAS compared with only 4 (44%) of controls. Moderate-severe OSAS was present in 15 (54%) of cases compared to only 1 (11%) of controls. Intermittent sleep-associated hypoxia and REM sleep deficits were also more frequent in cases. Across all subjects, prior tonsillectomy was not related to the presence or absence of OSAS. Our findings suggest that OSAS may be a common co-morbidity in adolescents and younger adults with DS and depression. Recognition of this association maybe critical to understanding the pathogenesis and management of mood-related disorders, and functional decline in affected individuals. © 2013 Wiley Periodicals, Inc. HubMed – depression

Estrogen, predominantly via estrogen receptor ?, attenuates postpartum-induced anxiety- and depression-like behaviors in female rats.

Endocrinology. 2013 Aug 2;
Furuta M, Numakawa T, Chiba S, Ninomiya M, Kajiyama Y, Adachi N, Akema T, Kunugi H

Contributions from estrogen receptor subtypes (ER? and ER?) to postpartum anxiogenic and depressive responses remain unresolved in rats. Using the elevated-plus maze (EPM) and forced swim (FS) tests, we confirmed that primiparous rats exhibited anxiogenic and depressive responses 3 weeks postpartum, improved 5 weeks postpartum (EPM), and recovered at 5 (FS) or 10 weeks postpartum (EPM) compared with diestrus nulliparous females. Immunohistochemistry suggested that these behavioral changes were temporally associated with decreased ER? but not ER? expression in the medial amygdala (MEA). Additionally, ER? expression in the medial preoptic area (MPOA) significantly increased 10 weeks postpartum. Brain-derived neurotrophic factor (BDNF) expression was significantly elevated in the MEA 3 weeks postpartum. BDNF receptor tropomyosin-related kinase (TrkB) expression was significantly elevated in the MEA at 3 and 10 weeks, but not at 5 weeks postpartum. The phosphorylation of extracellular signal-regulated kinase 2 (pERK2) in the MEA, MPOA and hippocampal CA1 region was significantly elevated 3 and 5 weeks postpartum. The effects of single daily subcutaneous injections of the ER|ga-selective agonist, propyl pyrazoletriol (PPT); ER?-selective agonist, diarylpropionitrile (DPN); 17?-estradiol (E2); and vehicle for 6 days in primiparous rats were assessed. PPT and E2 significantly produced anxiolytic and antidepressant actions in the EPM and FS tests, but PPT to a lesser degree than E2 in the EPM test. DPN affected the EPM test, but was not significantly different from vehicle. BDNF expression was significantly increased 3 weeks postpartum by all treatments in the MPOA, but not the CA1 and MEA. E2 and PPT treatment significantly increased TrkB and pERK1/2 expression in the MEA and MPOA, and increased pERK1/2 expression in the CA1.The onset of anxiety- and depression-like behaviors in postpartum rats may be partly caused by a complex estrogen-mediated mechanism; nevertheless, changes in the ER?-related system, likely in the MEA, are predominantly involved. HubMed – depression