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  • Springer Science and Business Media LLC  (2)
  • Dwork, Andrew J.  (2)
  • English  (2)
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  • Springer Science and Business Media LLC  (2)
Language
  • English  (2)
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  • 1
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-12-14)
    Abstract: Serotonin neurotransmitter deficits are reported in suicide, major depressive disorder (MDD) and alcohol use disorder (AUD). To compare pathophysiology in these disorders, we mapped brain serotonin transporter (SERT), 5-HT 1A , and 5-HT 2A receptor binding throughout prefrontal cortex and in anterior cingulate cortex postmortem. Cases and controls died suddenly minimizing agonal effects and had a postmortem interval ≤24 h to avoid compromised brain integrity. Neuropathology and toxicology confirmed absence of neuropathology and psychotropic medications. For most subjects (167 of 232), a DSM-IV Axis I diagnosis was made by psychological autopsy. Autoradiography was performed in right hemisphere coronal sections at a pre-genual level. Linear model analyses included sex and age with group and Brodmann area as interaction terms. SERT binding was lower in suicides ( p  = 0.004) independent of sex (females  〈  males, p   〈  0.0001), however, the lower SERT binding was dependent on MDD diagnosis ( p  = 0.014). Higher SERT binding was associated with diagnosis of alcoholism ( p  = 0.012). 5-HT 1A binding was greater in suicides ( p   〈  0.001), independent of MDD ( p  = 0.168). Alcoholism was associated with higher 5-HT 1A binding ( p   〈  0.001) but only in suicides ( p   〈  0.001). 5-HT 2A binding was greater in suicides ( p   〈  0.001) only when including MDD ( p  = 0.117) and alcoholism ( p  = 0.148) in the model. Reported childhood adversity was associated with higher SERT and 5-HT 1A binding ( p  = 0.004) in nonsuicides and higher 5-HT 2A binding ( p   〈  0.001). Low SERT and more 5-HT 1A and 5-HT 2A binding in the neocortex in depressed suicides is dependent on Axis I diagnosis and reported childhood adversity. Findings in alcoholism differed from those in depression and suicide indicating a distinct serotonin system pathophysiology.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2609311-X
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  • 2
    In: Molecular Psychiatry, Springer Science and Business Media LLC
    Abstract: Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules ( p 〈 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity ( p 〈 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability.
    Type of Medium: Online Resource
    ISSN: 1359-4184 , 1476-5578
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 1502531-7
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