Similarities and dissimilarities between psychiatric cluster disorders

Abstract

The common molecular mechanisms underlying psychiatric disorders are not well understood. Prior attempts to assess the pathological mechanisms responsible for psychiatric disorders have been limited by biased selection of comparable disorders, datasets/cohort availability, and challenges with data normalization. Here, using DisGeNET, a gene-disease associations database, we sought to expand such investigations in terms of number and types of diseases. In a top-down manner, we analyzed an unbiased cluster of 36 psychiatric disorders and comorbid conditions at biological pathway, cell-type, drug-target, and chromosome levels and deployed density index, a novel metric to quantify similarities (close to 1) and dissimilarities (close to 0) between these disorders at each level. At pathway level, we show that cognition and neurotransmission drive the similarity and are involved across all disorders, whereas immune-system and signal-response coupling (cell surface receptors, signal transduction, gene expression, and metabolic process) drives the dissimilarity and are involved with specific disorders. The analysis at the drug-target level supports the involvement of neurotransmission-related changes across these disorders. At cell-type level, dendrite-targeting interneurons, across all layers, are most involved. Finally, by matching the clustering pattern at each level of analysis, we showed that the similarity between the disorders is influenced most at the chromosomal level and to some extent at the cellular level. Together, these findings provide first insights into distinct cellular and molecular pathologies, druggable mechanisms associated with several psychiatric disorders and comorbid conditions and demonstrate that similarities between these disorders originate at the chromosome level and disperse in a bottom-up manner at cellular and pathway levels.

A Retrospective Study on the Factors Associated with Long-Stay Hospitalization in a Child Neuropsychiatry Unit

“…On the other, 24% of males receive a diagnosis of behavioral disorder compared to 8% of females. These percentages further confirm the results of previous studies, according to which internalizing disorders are more prevalent in females and, vice versa, externalizing disorders are more prevalent in males [8,43,44], as gender differences are linked to several different factors: genetic vulnerability, hormonal and neuropsychological changes, differences in personality, different coping styles, and cultural and social beliefs [43,45,46].…”

Comorbid chronic pain and depression: Shared risk factors and differential antidepressant effectiveness

“…As the AGDS employed phenotyping across an extensive range of complex traits 104 , on balance it was not feasible to also collect detailed information from participants on dosages and (polypharmacy) combinations taken of the prescribed antidepressants 105 ; the duration and magnitude of benefits (e.g., for cost-effectiveness analyses) 66,106,107 ; drug tolerability and adverse events 66,108–113 ; adjunct psychological therapies and multidisciplinary treatment/rehabilitation programs; 114 other prescribed pain pharmacotherapies and questionnaires. 115–119 Further pharmacoepidemiological studies focusing on chronic pain and a large range of psychiatric comorbidities 51,52,120 can directly address and collect data on these specific issues. As the current data were based on self-reported responses, they may also be subject to a degree of participant recall bias (e.g., time-specific details).…”

“…To further assess differences in effectiveness between specific antidepressants, targeted interventional trials can directly address the other phenotypes not captured in the current study. Nevertheless, our large-scale data-driven approach — like recent human genetic 36–52 and neuroimaging 57–59 antidepressant treatment studies — have revealed novel insights into the relationship between chronic pain and depression. Along with animal model and human pharmacogenetic studies 53– 56,118,119,123–127 , there is also independent converging evidence for the critical role of subcortical brain regions in mediating pain and mood.…”

“…3,32–34 However, the evidence for comorbid psychiatric disorders predicting pain intensity and worse outcomes is much weaker. 18,35 Nevertheless, recent large-scale human genetic studies, 36–52 animal models 53–56 and neuroimaging in antidepressant treatment trials 57–59 have made essential inroads towards delineating the causal mechanisms between chronic pain and depression.…”

Molecular signatures from multi‐omics of autism spectrum disorders and schizophrenia

“…Although each of these approaches are independent of the other, a multi-disciplinary omics study which aims to combine the results of each of these approaches may help to sort out the complex etiology of psychiatric disorders. Indeed, an integrative systems biology approach has been previously used for ASD (Briscoe & Marín, 2020;De Rubeis et al, 2014;Parikshak et al, 2015;Smail et al, 2021;Willsey et al, 2018).…”