Low digit ratio (2D:4D) in male suicide victims

Lenz, Bernd; Thiem, Daniel G. E.; Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Stoessel, Christina; Betz, P.; Kornhuber, Johannes

doi:10.1007/s00702-016-1608-4

Cited by 24 publications

(24 citation statements)

References 26 publications

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“…Interestingly, the importance of the prenatal period was suggested by the association of restricted fetal growth with SB in adulthood [52]. Molecular evidence for prenatal effects in SB is scarce, but recent observation report about a low digit ratio (2D:4D) in male suicide victims, a trait which is a proxy for the prenatal exposure to androgens [53]. While the androgen receptor ( AR ) gene was not directly observed among our CNVs per se , AR has “guilt-by-association” in the PPI network presented here due to its central connectivity to the IGF1R , NDE1 , RB1 and AMH genes therein (if inserted into Fig F in S1 File; not shown), which is of interest to consider for future studies.…”

Section: Discussionmentioning

confidence: 99%

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study

Sokolowski

Wasserman

2016

PLoS ONE

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Suicidal behavior (SB) has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs), as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA) in offspring as main outcome (n = 660 trios). We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (<1%) and large (>100 kb) CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB) sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having increased SNP risk-allele burden. These observations may open up new avenues in the genetic etiology of SB.

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Section: Discussionmentioning

confidence: 99%

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study

Sokolowski

Wasserman

2016

PLoS ONE

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“…For example, lower (prenatally more androgenized) 2D:4D has been reported in individuals with poorer health (Rapoza 2017 ), prostate cancer (Mendes et al 2016 ), primary brain tumors (Bunevicius et al 2016 ), alcohol dependence (Kornhuber et al 2011 ; Han et al 2016 ; Lenz et al 2017 ), anorexia nervosa in females (Quinton et al 2011 ), Alzheimer’s disease in females (Vladeanu et al 2014 ), and aggression-related injuries (Joyce et al 2013 ; O’Briain et al 2017 ). In addition, we recently provided the initial evidence for lower 2D:4D values in males who had died from suicide in comparison to males with other causes of death (Lenz et al 2016 ). Higher (prenatally more estrogenized) 2D:4D has also been associated with lethal diseases such as breast cancer (Muller et al 2012 ; Hong et al 2014 ), cervical dysplasia (Brabin et al 2008 ), oral squamous cell carcinoma in males (Nicolás Hopp and Jorge 2011 ), gastric cancer (Nicolás Hopp et al 2013 ), disordered eating in males (Smith et al 2010 ), Alzheimer’s disease in males (Vladeanu et al 2014 ), coronary heart disease (Lu et al 2015 ), and myocardial infarction (Kyriakidis et al 2010 ).…”

Section: Introductionmentioning

confidence: 93%

“…Moreover, we used a hypothesis-free approach to further explore associations with specific causes of death, as defined by WHO. Many studies have shown sex-dependent relationships between 2D:4D and illness with stronger or exclusively significant associations in males, suggesting that prenatal sex hormone priming might be more relevant to lifetime health status in males in comparison to females (Martin et al 1999 ; Bailey and Hurd 2005 ; Martel et al 2008 ; Collinson et al 2010 ; Kyriakidis et al 2010 ; Kornhuber et al 2011 ; Nicolás Hopp et al 2013 ; Portnoy et al 2015 ; Lenz et al 2016 , 2017 ; Rapoza 2017 ) (but see also: Smedley et al 2014 ; O’Briain et al 2017 ). Thus, we analyzed sex-specifically whether normalized 2D:4D correlated with normalized life expectancy, suicide rates, and death rates from other causes across nations.…”

Section: Introductionmentioning

confidence: 99%

Cross-national gender variations of digit ratio (2D:4D) correlate with life expectancy, suicide rate, and other causes of death

Lenz

Kornhuber

2017

J Neural Transm

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The second-to-fourth finger length ratio (2D:4D) is an indication of prenatal sex hormone exposure, and has sex-specifically been associated with several lethal illnesses including ischemic heart disease, diverse cancers, and suicide. Our primary aim was to verify that 2D:4D sex-specifically relates to life expectancy and suicide numbers on a national level (23 countries). We also used a hypothesis-free approach to investigate associations with other causes of death [p value adjustment for multiple hypothesis testing using the false discovery rate procedure (FDR)]. All parameters were normalized to the national mean (of males and females) and analyzed across nations. Normalized male 2D:4D correlated positively with normalized male life expectancy (at birth, r = 0.46, p = 0.029; at the age of 60, r = 0.44, p = 0.038) and negatively with normalized male suicide rates (r = − 0.49, p = 0.017). In the exploratory analyses, the normalized male 2D:4D values were negatively associated with the normalized male deaths rates from communicable, maternal, perinatal, and nutritional conditions [r = − 0.65, p(FDR) = 0.011], respiratory infections [r = − 0.69, p(FDR) = 0.008], asthma [r = − 0.65, p(FDR) = 0.011], neurological conditions [r = − 0.56, p(FDR) = 0.046], and Alzheimer’s disease and other dementias [r = − 0.59, p(FDR) = 0.036]. The normalized female parameters showed the same cross-national correlations. In line with the previous individual level findings, the results suggest that prenatal sex hormone effects are sex-specifically involved in suicide and neurological conditions. Moreover, we provide novel national level evidence that prenatal sex hormone priming may sex-specifically influence life expectancy and death risk from respiratory diseases.

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“…Values are presented as M ± SE. RMSSD = root mean square of successive differences died by suicide compared to men who had died by other means, while no statistically significant effects were observed for women (Lenz et al, 2016). However, another study did not identify an association between R2D4D and depressive symptoms (Austin, Manning, McInroy, & Mathews, 2002), while an additional study observed a positive association between R2D4D and depressive symptoms in women, but not in men (Smedley, McKain, & McKain, 2014).…”

Section: Lower 2d4d and Affectmentioning

confidence: 94%

Associations between digit ratio (2D4D), mood, and autonomic stress response in healthy men

et al. 2019

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The ratio between the length of the second (index) and the fourth (ring) finger (2D4D) is a putative biomarker of prenatal testosterone (T) exposure, with higher exposure leading to a smaller ratio. 2D4D has further been linked to mental and somatic disorders. Healthy male Swiss recruits (N = 245; Mage = 20.30 years) underwent a psychosocial stress test. Mood and salivary alpha‐amylase (sAA) were assessed before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. Additionally, 2D4D (right: R2D4D; left: L2D4D) was determined and divided into quartile groups. Correlation analysis showed no associations between R/L2D4D and outcome measures. Comparing calculated quartiles for R2D4D, subjects in the lowest R2D4D quartile expressed trendwise (p < 0.10) lower positive and higher negative affect, significantly elevated sAA activity (p < 0.05), but no HR and HRV differences at baseline as compared to subjects in the upper three quartiles. With regard to acute stress, subjects in the lowest as compared to subjects in the upper three R2D4D quartiles showed a higher increase of negative affect and a stronger cardiac response (p < 0.05), but no alterations in positive affect and sAA activity. Young healthy men in the lowest R2D4D quartile revealed a more negative affect and increased physiological activity at baseline and in response to acute stress. An exposure to high levels of prenatal T might constitute a risk factor potentially increasing vulnerability to stress‐related disorders in men.

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Low digit ratio (2D:4D) in male suicide victims

Cited by 24 publications

References 26 publications

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study

Cross-national gender variations of digit ratio (2D:4D) correlate with life expectancy, suicide rate, and other causes of death

Associations between digit ratio (2D4D), mood, and autonomic stress response in healthy men

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