Exploring Genetic Susceptibility to Internalizing Symptoms within the DSM: Network Analysis

This study conducts network analysis to explore genetic predispositions to internalizing mental disorder symptoms within the DSM framework. It focuses on single nucleotide polymorphisms (SNPs) in genes such as HTR_1A, TPH2, COMT, DRD₂, and BDNF, examining their connections to symptoms like depression, post-traumatic stress, panic, general anxiety, social phobia, and agoraphobia. Utilizing advanced network modeling based on the Ising model, we analyzed a sample of 312 twins (240 females; M_age = 25.14; SD = 7.81). This method estimates networks of items/symptoms and gene variants, providing insights into gene-symptom relationships. The study highlights significant associations between SNPs and internalizing symptoms, with a gene-specific emphasis. Notably, COMT, DRD₂, and HTR_1A genes show significant associations with particular symptoms, underscoring their gene-specific nature. In contrast, BDNF and TPH2 exhibit no significant relations to internalizing symptoms. The findings also reveal non-linear associations between symptoms and specific genes, with central symptoms in the network correlated to certain gene risk variants. A notable result is the lack of association between serotonin genes and depression, indicating the complexity of depressive symptoms’ genetic underpinnings. Strong genetic bases for social phobia and agoraphobia symptoms were observed, along with PTSD symptoms associated with the DRD₂ gene. This research provides detailed insights into gene-specific associations with internalizing symptoms, advocating for an integrative and dimensional approach in genetic studies of psychopathology. It emphasizes the importance of focusing on symptom-specific genetic pathways and contributes comprehensively to a deeper understanding of the biological foundations of psychopathological conditions.