The Neurobiological Pathway Towards Suicidal Ideation - Cerebrospinal Fluid Markers, Cognitive Impairment and Brain Imaging

Abstract

In recent years, there has been increasing recognition of neurobiological factors as critical contributors to the vulnerability underlying suicidal behavior. This thesis examines the associations between synaptic dysfunction, mild cognitive impairment, structural brain changes, and suicidal ideation within population-based samples of older adults. Paper I included 86 women from the year 1992 cohort of the Prospective Population Study of Women (PPSW), all of whom participated in psychiatric assessments and underwent lumbar puncture (LP). Paper II involved 916 participants drawn from both the PPSW and the year 2000 cohort of the Gothenburg H70 Birth cohort study. Cognitive status was evaluated using the Winblad et al. criteria. Paper III investigated 322 participants from the 2014 cohort of the Gothenburg H70 Birth Cohort Study who also underwent LP. Paper IV included 774 individuals from the same cohort who underwent brain magnetic resonance imaging (MRI). Paper I identified elevated cerebrospinal fluid (CSF) levels of YKL-40 and GAP-43 in women reporting past month suicidal ideation. Higher CSF GAP- 43 levels were also related to feelings of worthlessness. Paper II found that mild cognitive impairment (MCI) was associated with life-weariness and death wishes reported within the past year, as demonstrated in adjusted regression models. MCI was also related to lifetime experiences of life-weariness. Paper III identified a connection between high CSF Ng level and lifetime reports of life-weariness, death wishes, and thoughts of taking one’s own life, that remained after taking CSF levels of Aβ42, T-Tau, and P-Tau into account. Paper IV found that individuals with a lifetime history of serious suicidal ideation exhibited larger white matter lesions (WML) volumes compared to those without such ideation. However, this association did not persist after adjusting for relevant covariates in the logistic regression model. To conclude, these findings suggest that neurobiological factors—including synaptic dysfunction, cognitive impairment, and distinct structural brain changes—may contribute to suicidal ideation among older adults.