Clin Psychopharmacol Neurosci.  2021 Feb;19(1):26-45. 10.9758/cpn.2021.19.1.26.

Second-to-Fourth Digit Ratio (2D:4D) in Psychiatric Disorders: A Systematic Review of Case-control Studies

• Fusar-Poli L
• Rodolico A
• Sturiale S
• Carotenuto B
• Natale A
• Arillotta D
• Siafis S
• Signorelli MS
• Aguglia E

• KMID: 2513388
• DOI: http://doi.org/10.9758/cpn.2021.19.1.26

Abstract

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. In September 2019, we searched in Web of Knowledge, PsycINFO, Embase, and CINHAL, and retrieved 619 papers. We finally included 43 case-control studies which compared the 2D:4D ratio of patients with autism spectrum disorder (ASD) (n = 16), schizophrenia (n = 8), gender non-conformity (n = 7), addictions (n = 5), attention deficit-hyperactivity disorder (ADHD) (n = 4), mood disorders (n = 2), and intellectual disability (n = 1) to non-clinical controls. Meta-analyses showed that, overall, psychiatric patients had lower 2D:4D than healthy controls (n = 43, overall sample = 9,484, mean difference = −0.0056, 95% confidence interval from −0.0093 to −0.002, I ² = 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. 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.

Keyword

Meta-analysis; Mental disorders; Testosterone; Autism spectrum disorder; Attention deficit disorder with hyperactivity; Substance addiction.