Testosterone metabolism: a possible biological underpinning of non-verbal IQ in intellectually gifted girls

Abstract

The extraordinary giftedness is apparently a unique manifestation of a mutual interconnection between genes and environment. One of the possible etiological factors of intellectual giftedness is testosterone which is believed to affect the brain organization and function.The aim of our study was to analyze associations between 2D:4D digit ratio (a proxy of prenatal testosterone) and/or salivary testosterone levels with non-verbal IQ in intellectually gifted girls. Fifty-one girls with an age range of 10 to18 years and IQ scores higher than 130 were tested. Saliva samples were collected to obtain levels of salivary testosterone. 2D:4D digit ratio was measured on both hands as an indicator of prenatal testosterone. IQ parameters were assessed employing standardized set of tests. The CAG repeat polymorphism in exon 1 of the androgen receptor gene was analyzed to assess the sensitivity of androgen receptor. Testing of between-subjects effects proved significant interactions between right and left 2D:4D ratio, genetic variability in androgen receptor, and also salivary testosterone level with non-verbal IQ in gifted girls. Our results point out that the variability in parameters of androgenicity contributes to the variability of nonverbal IQ in gifted girls. However, the exact molecular mechanism of how testosterone acts on the brain and affects this cognitive domain remains still unclear.

Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia

“…Alternatively, this relationship may be an atypical reaction for females, as we found no association between CAG repeat length and circulating testosterone in our female control group. However, research on the relationship between CAG repeat length and peripheral testosterone levels in healthy females reports inconsistent associations [59-61, 91-93]. Circulating testosterone levels in our female controls were low and within a narrow range (0.06–0.3 ng/mL), possibly limiting our ability to find a significant correlation with CAG repeat length.…”

“…Thus, CAG repeat length is a potential AR genetic variant that can interact with circulating testosterone to modify brain response to testosterone and possibly schizophrenia symptom severity. The genetic CAG repeat length in AR is positively associated with circulating testosterone levels in both healthy men [53-58] and women [59-61]. While lower circulating testosterone is often found in men with schizophrenia [3-6], whether genetic variation in AR CAG repeat length is related to testosterone levels in patients with schizophrenia remains unknown.…”

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta‐analyses

“…The previous eight studies indicated that testosterone levels are negatively correlated with 2D:4D (Crewther & Cook, ; Durdiaková et al, ; García‐Cruz et al, ; Klimek, Galbarczyk, Nenko, Alvarado, & Jasienska, ; Manning et al, ; Muller et al, ; Perciavalle et al, ; Tan, ), while other two studies showed that they have a strong positive relationship (Chen, Decety, Huang, Chen, & Cheng, ; Durdiaková et al, , ; Oświecimska et al, ). Interestingly, a significant relationship was not found referring to the other 32 studies (Almasry, Domiaty, Algaidi, Elbastawisy, & Safwat, ; Bang et al, ; Benderlioglu & Nelson, ; Borniger, Chaudhry, & Muehlenbein, ; Borráz‐León, Cerda‐Molina, Choi, & Mayagoitia‐Novales, ; Campbell et al, ; Coco et al, ; Durdiaková et al, ; Falter, Arroyo, & Davis, ; Flegr, Lindova, Pivonkova, & Havlicek, ; Folland et al, ; Georgiev, Ryan, Gettler, McDade, & Kuzawa, ; Hönekopp et al, ; Kallai et al, ; Kempel et al, ; Kilduff et al, ; Kubranska et al, ; Li et al, ; Lujan, Bloski, Chizen, Lehotay, & Pierson, ; Maestripieri, Baran, Sapienza, & Zingales, ; Manning et al, ; McIntyre, Li, Chapman, Lipson, & Ellison, ; Neave, Laing, Fink, & Manning, ; Oh, Kim, Yoon, Kim, & Kim, ; Portnoy et al, ; Richards, Klimek, Jasienska, & Marcinkowska, ; Roney & Maestripieri, ; Unal, Urun Unal, Balevi, Tol, & Uyar, ; Vermeersch, T'Sjoen, Kaufman, & Vincke, ; Whitehouse et al, ; Yang, Gray, Zhang, & Pope, ; Zhang et al, ). Regarding our replication study, the results indicate that there is no a significant association between them.…”

“…Unfortunately, two early meta‐analyses indicated that AR (CAG)n is not significantly associated with the ratio (Hönekopp, ; Voracek, ). However, the conclusion from the meta‐analyses were not supported by the subsequent studies with new samples (Durdiaková et al, ; Durdiaková, Celec, Laznibatova, Minarik, & Ostatnikova, ; Warrington et al, ). Thus, we performed an update meta‐analysis to address the issues on such relationship.…”

“…Such a relationship in another study, however, was described as a significant negative correlation (De Naeyer et al, ). Furthermore, 12 reports demonstrated that they don't have any significant correlation (Butovskaya et al, ; Durdiaková et al, , ; Folland, Mc Cauley, Phypers, Hanson, & Mastana, ; Hampson & Sankar, ; Hurd et al, ; Kubranska et al, ; Latourelle, Elwess, & Elwess, ; Loehlin, Medland, & Martin, ; Mas et al, ; Zhang, Dang et al, ). As for the previous findings in females, Warrington's study (Warrington et al, ) indicated that the length is positively related to 2D:4D, while other five studies didn't find a significant correlation between them (Durdiaková et al, ; Latourelle et al, ; Loehlin et al, ; Mas et al, ; Zhang, Dang et al, ).…”