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Psychiatric and neurological diseases present substantial challenges in healthcare, affecting millions of individuals worldwide. Conditions such as depression, trigeminal neuralgia (TN), and narcolepsy have a profound impact on the quality of life for both patients and their families. The complex nature of these conditions necessitates the development of innovative diagnostic and treatment strategies. In recent years, the importance of biomarkers in understanding, diagnosing, and managing psychiatric and neurological diseases has emerged as a promising field of research. In the current thesis, five studies were conducted to identify candidate biomarkers in depression, TN, and narcolepsy. Study I validated depression-associated genetic variants in the UK Biobank (UKB) cohort, with transcriptome and DNA methylation analyses in independent datasets. Eight single nucleotide polymorphisms corresponding to six protein-coding genes (TNXB, NCAM1, LTBP3, BTN3A2, DAG1, FHIT) were strongly linked to depression. Study II analyzed 92 proteins in cerebrospinal fluid and serum from TN patients, compared with multiple sclerosis patients and controls. Several proteins, including SFRP1, FKBP5, and TBCB, were elevated in TN, suggesting their relevance in disease mechanisms. Study III examined protein levels in adolescents assessed for depression in the domestic Psychiatric Health in Adolescent Study (PSY cohort) in Sweden, with transcriptome validation in independent cohorts. Key findings highlighted protein and transcriptomic differences, particularly in PPP3R1, implicating the calcineurin pathway and prefrontal cortex in depression. Study IV explored genetic evidence in the UKB to validate the role of 17 proteins from previous studies in TN. Novel associations were identified with C8B (complement system) and MFGE8 (neuroinflammation regulation), highlighting their roles in TN pathology. Finally, Study V assessed protein biomarkers in narcolepsy using Swedish and Finnish cohorts, with transcriptome validation in an independent dataset. The identified candidate proteins were indicative of neural development involving survival, growth, and differentiation (UNC5C, VWC2, GFR-alpha-1, ADAM23), oxidative stress (HAGH), immune response (CLEC10A), and cell cycle regulation (ILKAP). Collectively, these studies identify potential biomarkers across these conditions, offering insights into their underlying mechanisms. The findings expand our understanding of psychiatric and neurological health and may inform future research and therapeutic strategies.