Second-to-fourth digit ratio (2D:4D) in psychiatric disorders: A systematic review of case-control studies
Laura Fusar-Poli 1*, Alessandro Rodolico 1, Serena Sturiale 1, Bianca Carotenuto 1, Antimo Natale 1, Davide Arillotta 1, Spyridon Siafis 2, Maria Salvina Signorelli 1, Eugenio Aguglia 1
1Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, Italy, 2Department of Psychiatry and Psychotherapy, School of Medicine, Technische Universität München, Germany
Received: April 30, 2020; Revised: July 24, 2020; Accepted: July 26, 2020; Published online: July 26, 2020.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: The second-to-fourth digit ratio (2D:4D) is an indirect, retrospective, non-invasive measure that correlates negatively with intrauterine exposure to testosterone. The present meta-analysis aimed to evaluate if 2D:4D differs between patients with psychiatric disorders and controls.
Methods: In September 2019, we searched in Web of Knowledge, PsycINFO, Embase, and CINHAL, and retrieved 619 papers.
Results: We finally included 43 case-control studies which compared the 2D:4D ratio of patients with ASD (16), schizophrenia (8), gender non-conformity (7), addictions (5), ADHD (4), mood disorders (2), and intellectual disability (1) to non-clinical controls. Meta-analyses showed that, overall, psychiatric patients had lower 2D:4D than healthy controls (n = 43, overall sample = 9484, MD = -0.0056, 95% CI from -0.0093 to -0.002, I2 = 74%), with more pronounced differences in the right hand, males, and children. Considering psychiatric disorders individually, significant differences were found in the ASD, ADHD, and addictions groups, in which 2D:4D was significantly lower than healthy controls. Conversely, the right hand of males with schizophrenia showed higher 2D:4D than healthy controls. No other significant differences were detected.
Conclusion: Although our results need to be cautiously interpreted and find limited applications in clinical practice, they may suggest that 2D:4D is altered in some psychopathological conditions, underlining the role of prenatal exposure to sex steroids in the etiology of psychiatric disorders.
Keywords: digit ratio, psychiatric disorders, fetal testosterone, meta-analysis, autism spectrum disorder, ADHD, addictions, gender dysphoria, mood disorders, schizophrenia, intellectual disability, sex steroids

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