TY - JOUR

T1 - Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods

AU - Козлова, Алёна Алексеевна

AU - Ваганова, Анастасия Николаевна

AU - Родионов, Роман Николаевич

AU - Гайнетдинов, Рауль Радикович

AU - Bernhardt, Nadine

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/10

Y1 - 2022/10

N2 - The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study’s objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects. There were no significant differences in DDAH1 and DDAH2 expression levels in schizophrenia or bipolar disorder patients compared to controls. Meanwhile, the data suggest that in patients, DDAH1 and DDHA2 undergo a functional shift mirrored in changes in co-expressed gene patterns. This disarrangement appears in the loss of expression level correlations between DDAH1 or DDAH2 and genes associated with psychiatric disorders and reduced functional similarity of DDAH1 or DDAH2 co-expressed genes in the patient groups. Our findings evidence the possible involvement of DDAH1 and DDAH2 in neuropsychiatric disorder development, but the underlying mechanisms need experimental validation.

AB - The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study’s objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects. There were no significant differences in DDAH1 and DDAH2 expression levels in schizophrenia or bipolar disorder patients compared to controls. Meanwhile, the data suggest that in patients, DDAH1 and DDHA2 undergo a functional shift mirrored in changes in co-expressed gene patterns. This disarrangement appears in the loss of expression level correlations between DDAH1 or DDAH2 and genes associated with psychiatric disorders and reduced functional similarity of DDAH1 or DDAH2 co-expressed genes in the patient groups. Our findings evidence the possible involvement of DDAH1 and DDAH2 in neuropsychiatric disorder development, but the underlying mechanisms need experimental validation.

KW - DDAH1

KW - DDAH2

KW - bipolar disorder

KW - schizophrenia

KW - Humans

KW - Biological Products

KW - Nitric Oxide Synthase

KW - Amidohydrolases/genetics

KW - Arginine/metabolism

KW - Mental Disorders/genetics

KW - Nitric Oxide/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85139811133&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c2a3e98b-bf52-3dc2-b0f7-e46834ddce83/

U2 - 10.3390/ijms231911902

DO - 10.3390/ijms231911902

M3 - Article

C2 - 36233204

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 19

M1 - 11902

ER -