Functional Polymorphisms in BDNF and COMT Genes Are Associated with Objective Differences in Arithmetical Functioning in a Sample of Young Adults

Abstract

Background: Understanding the molecular genetics of complex human behaviors and functions remains a substantial challenge for the neurosciences. Previous studies have shown a genetic basis for individual differences in mathematical functioning; however, the specific genes remain to be completely identified. In the present study, we explored the possibility that 2 functional polymorphisms in candidate genes could be associated with differences in arithmetical performance. Methods: A computerized test to analyze performance in basic arithmetical calculations (additions and subtractions) was applied to 168 healthy young Colombian participants using the PEBL (Psychology Experiment Building Language) battery. DNA samples were genotyped for 2 functional SNPs in candidate genes: brain-derived neurotrophic factor (BDNF)-Val66Met and catechol-O-methyltransferase (COMT)-Val158Met. Results: We found significant differences for arithmetical processing scores between genotypes. For BDNF, Val/Val subjects had a worse performance (p value: 0.025) and for COMT, Val/Val carriers had a better performance (p value: 0.006). A multivariate model, including both BDNF and COMT genes, accounted for 7.1% of the variance in math processing scores. Discussion: To our knowledge, this is the first study finding associations of polymorphisms in BDNF and COMT genes with quantitative measures of numerical aptitude in healthy young participants. A future study of other genes involved in neural plasticity could be helpful to identify genetic correlates of arithmetical functioning, which will be important for the understanding of normal human behaviors and related neuropsychiatric disorders.

Impact of brain‐derived neurotrophic factor genetic polymorphism on cognition: A systematic review

“…The included studies examined genetic association with neurocognition in healthy patients and other disease states. In total, 40 of the 82 reviewed studies (48.8%) (Aas et al., ; Alfimova, Korovaitseva, Lezheiko, & Golimbet, ; Altmann et al., ; Avgan et al., ; Barbey et al., ; Canivet et al., ; Cao et al., ; De Beaumont, Fiocco, Quesnel, Lupien, & Poirier, ; Egan, Kojima, & Callicott, ; Freundlieb et al., ; Gajewski, Hengstler, Golka, Falkenstein, & Beste, ; Gong et al., ; Gonzalez et al., ; Gonzalez‐Giraldo et al., ; Gosselin et al., ; Ho, Andreasen, Dawson, & Wassink, ; Huang et al., ; Jasinska et al., ; Kim et al., ; Lamb, Thompson, McKay, Waldie, & Kirk, ; Lee, Baek, & Kim, ; Lim et al., , ; Miyajima et al., ; McAllister et al., ; Nagata, Shinagawa, Nukariya, Yamada, & Nakayama, ; Narayanan et al., ; Ng et al., ; Raz, Rodrigue, Kennedy, & Land, ; Richter‐Schmidinger et al., ; Rybakowski, Borkoswka, Czerski, Skibinska, & Hauser, ; Rybakowski et al., ; Schofield et al., ; Szabo et al., ; Tan et al., ; Tukel et al., ; van der Kolk et al., ; Yin, Hou, Wang, Sui, & Yuan, ; Yogeetha et al., ; Zhang et al., ) reported a significant association between Val66Met polymorphism and the neurocognitive domains of interest.…”

“…The included studies had healthy controls ( n = 36) (Alfimova et al., ; Avgan et al., ; Beste, Schneider, Epplen, & Arning, ; Bombardier, Beauchemin, Gosselin, Poirier, & De Beaumont, ; Cathomas, Vogler, Euler‐Sigmund, de Quervain, & Papassotiropoulos, ; Canivet et al., ; Chen et al., , ; Dennis et al., ; De Beaumont et al., ; Erickson et al., ; Freundlieb et al., ; Gajewski et al., ; Gong et al., ; Gonzalez‐Giraldo et al., ; Gosselin et al., ; Huang et al., ; Jasinska et al., ; Karnik et al., ; Kennedy et al., ; Lim et al., ; Liu et al., ; Lamb et al., ; Miyajima et al., ; Montag et al., ; Raz et al., ; Richter‐Schmidinger et al., ; Schofield et al., ; Stuart, Summers, Valenzuela, & Vickers, ; Thow et al., ; Voineskos et al., ; Ward et al., , ; Wilkosc et al., ; Wegman, Tyborowska, Hoogman, Arias Vásquez, & Janzen, ; Yogeetha et al., ), dementia ( n = 1) (Kim et al., ), Alzheimer’s ( n = 3) (Gomar, Conejero‐Goldberg, Huey, Davies, & Goldberg, ; Lim et al., ; Lin et al., ), Parkinson’s ( n = 1) (Bialecka et al., ), cardiovascular disease ( n = 2) (Swardfager et al., ; Szabo et al., ), obsessive‐compulsive disease ( n = 1) (Tukel et al., ), multiple sclerosis ( n = 1) (Fera et al., ), psychosis ( n = 2) (Aas et al., ; Martinho et al., ), depression/anxiety disorders ( n = 2) (Molendijk et al., ; Strauss, Barr, & George, ), brain injury ( n = 2) (McAllister et al., ; Narayanan et al., ), amnestic mild cognitive impairment ( n = 1) (Yu et al., ), schizophrenia and bipolar disorders ( n = 9) (Cao et al., ; Egan et al., ; Ho et al.,…”

“…Nineteen of these identified studies (30.2%) (Aas et al., ; Canivet et al., ; Cao et al., ; De Beaumont et al., ; Egan et al., ; Gong et al., ; Gosselin et al., ; Ho et al., ; Jasinska et al., ; Lamb et al., ; Lim et al., ; Miyajima et al., ; Narayanan et al., ; Richter‐Schmidinger et al., ; Raz et al., ; Schofield et al., ; Tan et al., ; Tukel et al., ; Yogeetha et al., ) favored Val/Val homozygotes under the memory domain, in healthy controls and populations with psychosis, depression, Alzheimer’s disease, brain injury, obsessive‐compulsive disorder, and schizophrenia, respectively. Conversely, Met carriers were found to perform better in memory tasks in seven of such studies (11.1%) that evaluate healthy controls and populations with cardiovascular diseases and schizophrenia (Alfimova et al., ; Avgan et al., ; Gajewski et al., ; Gonzalez‐Giraldo et al., ; Huang et al., ; Kim et al., ; Szabo et al., ).…”

Schizophrenia and Human Self-Domestication: An Evolutionary Linguistics Approach

“…BDNF encodes a nerve growth factor needed for neuronal survival and synaptic plasticity. Common variants/polymorphisms of the gene have been associated with specific cognitive processes [see Goldberg and Weinberger 2004;González-Giraldo et al, 2014;Jasińska et al, 2016;and Wegman et al, 2016] and with the cognitive performance of people suffering from neuropsychiatric conditions. In particular, abnormally low levels of BDNF have been detected in schizophrenics [Palomino et al, 2006].…”

No Association ofBDNF,COMT,MAOA,SLC6A3, andSLC6A4Genes and Depressive Symptoms in a Sample of Healthy Colombian Subjects

“…DNA samples were adjusted to a final concentration of 10 ng/ µ L and stored at 4°C until being used [ 27 ]. Genotyping assays for the 5 candidate genes were carried out as previously described [ 18 , 20 , 28 , 29 ], using methods based on qPCR and conventional PCR and agarose gel electrophoresis. PCR reactions were carried out in a Labnet MultiGene thermal cycler (Labnet International Inc., Edison, NJ, USA) and their products were separated at 140 V in 2% agarose gel stained with SYBR Safe (Invitrogen, Carlsbad, CA, USA).…”