Ventral prefrontal serotonin 1A receptor binding: a neural marker of vulnerability for mood disorder and suicidal behavior?

Autor: Ainsley K. Burke, Francesca Zanderigo, Mohammad Lesanpezeshki, Nadine M. Melhem, Elizabeth Bartlett, Jeffrey M. Miller, J. John Mann, David A. Brent, Pantazatos S
Rok vydání: 2022
Předmět:
Zdroj: Mol Psychiatry
ISSN: 1476-5578
1359-4184
Popis: BACKGROUND: Mood disorders and suicidal behavior have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT1A) binding potential. However, it is unclear whether these alterations reflect heritable risk or epigenetic effects of childhood, compensatory mechanisms, or illness-related changes. We sought to separate effects on 5-HT1A binding due to mood disorder, suicidal behavior, and risk and resilience to both by examining high familial risk individuals (HR) who have passed through the age of greatest risk for psychopathology onset. METHODS: PET imaging quantified 5-HT1A binding potential BPND using [11C]CUMI-101 in healthy volunteers (HV, N=23) and three groups with one or more relatives with early-onset mood disorder and suicide attempt: 1. unaffected HR (N=23); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N=26); and 3. HR-MOOD with previous suicide attempt (HR-MOOD+SA, N=20). Findings were tested in two independent cohorts of low risk individuals (HV, MOOD, and MOOD+SA, total N=185). We tested for regional BPND differences and whether brain-wide patterns distinguished between groups. RESULTS: Low ventral prefrontal 5-HT1A BPND in MOOD+SA was found across three independent cohorts. Brain-wide 5-HT1A BPND patterns distinguished HR-MOOD+SA from HV. An endophenotype associated with familial risk was not observed. CONCLUSIONS: Low ventral prefrontal 5-HT1A BPND may reflect suicide-related pathology. Further studies are needed to determine if higher ventral prefrontal 5-HT1A BPND confers resilience for developing suicidal behavior in the context of mood disorders. If so, it could be a potential suicide prevention target.
Databáze: OpenAIRE
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