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      Parental brain‐derived neurotrophic factor genotype, child prosociality, and their interaction as predictors of parents’ warmth

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          Abstract

          Background

          Parental warmth has been associated with various child behaviors, from effortful control to callous‐unemotional traits. Factors that have been shown to affect parental warmth include heritability and child behavior. However, there is limited knowledge about which specific genes are involved, how they interact with child behavior, how they affect differential parenting, and how they affect fathers. We examined what affects paternal and maternal warmth by focusing on the child's prosocial behavior and parents’ genotype, specifically a Valine to Methionine substitution at codon 66 in the brain‐derived neurotrophic factor ( BDNF) gene.

          Methods

          Data was available from a sample of 6.5 year‐old twins, consisting of 369 mothers and 663 children and 255 fathers and 458 children. Self‐reports were used to assess mothers’ and fathers’ warmth. Child prosociality was assessed with the other‐parent report and experimental assessments.

          Results

          Mothers’ warmth was not affected by their BDNF genotype, neither as a main effect nor in an interaction with child prosociality. Fathers with the Met allele scored higher on warmth. Additionally, there was a significant interaction between fathers’ BDNF genotype and child prosociality. For fathers with the Met allele there was a positive association between warmth and child prosociality. Conversely, for fathers with the Val/Val genotype there was no association between warmth and child prosociality. Results were repeated longitudinally in a subsample with data on age 8–9 years. A direct within family analysis showed that fathers with the Met allele were more likely than Val/Val carriers to exhibit differential parenting toward twins who differed in their prosocial behavior. The same pattern of findings was found with mother‐rated and experimentally assessed prosociality.

          Conclusions

          These results shed light on the genetic and environmental underpinnings of paternal behavior and differential parenting.

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          Most cited references52

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          The impact of age, weight and gender on BDNF levels in human platelets and plasma.

          Brain-derived neurotrophic factor (BDNF) is a key mediator of neuronal plasticity in the adult. BDNF is known to be stored in human platelets and to circulate in plasma, but the regulation and function of BDNF in peripheral blood is still poorly understood. In this prospective study, we have examined 140 healthy, non-allergic adults (20-60 years old) to elucidate the impact of age and physical parameters on BDNF levels in human platelets and plasma. There was a wide concentration range of BDNF in serum (median: 22.6 ng/ml), platelets (median: 92.7 pg/10(6) platelets) and plasma (median: 92.5 pg/ml). BDNF levels in plasma decreased significantly with increasing age or weight, whereas platelet levels did not. When matched for weight, there were no significant gender differences regarding BDNF plasma levels. However, women displayed significantly lower platelet BDNF levels than men. In addition, platelet BDNF levels changed during the menstrual cycle. In conclusion, we demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF levels in peripheral blood.
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            Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons.

            Brain-derived neurotrophic factor (BDNF) plays a critical role in nervous system and cardiovascular development and function. Recently, a common single nucleotide polymorphism in the bdnf gene, resulting in a valine to methionine substitution in the prodomain (BDNF(Met)), has been shown to lead to memory impairment and susceptibility to neuropsychiatric disorders in humans heterozygous for the variant BDNF. When expressed by itself in hippocampal neurons, less BDNF(Met) is secreted in an activity-dependent manner. The nature of the cellular defect when both BDNF(Met) and wild-type BDNF (BDNF(Val)) are present in the same cell is not known. Given that this is the predominant expression profile in humans, we examined the effect of coexpressed BDNF(Met) on BDNF(Val) intracellular trafficking and processing. Our data indicate that abnormal trafficking of BDNF(Met) occurred only in neuronal and neurosecretory cells and that BDNF(Met) could alter the intracellular distribution and activity-dependent secretion of BDNF(Val). We determined that, when coexpressed in the same cell, approximately 70% of the variant BDNF forms BDNF(Val).BDNF(Met) heterodimers, which are inefficiently sorted into secretory granules resulting in a quantitative decreased secretion. Finally, we determined the form of BDNF secreted in an activity-dependent manner and observed no differences in the forms of BDNF(Met) or the BDNF(Val).BDNF(Met) heterodimer compared with BDNF(Val). Together, these findings indicate that components of the regulated secretory machinery interacts specifically with a signal in the BDNF prodomain and that perturbations in BDNF trafficking may lead to selective impairment in CNS function.
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              Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors.

              Indirect evidence suggests that loss of brain-derived neurotrophic factor (BDNF) from forebrain regions contributes to an individual's vulnerability for depression, whereas upregulation of BDNF in these regions is suggested to mediate the therapeutic effect of antidepressants. We have tested this hypothesis by generating two independent lines of conditional BDNF knockout mice in which the BDNF gene is deleted selectively in forebrain. We show that male conditional knockouts exhibit hyperactivity but normal depression-related behaviors. In contrast, female conditional knockouts display normal locomotor activity but a striking increase in depression-like behavior. We also demonstrate that loss of BDNF in both male and female mice attenuates the actions of the antidepressant desipramine in the forced swim test. These gender differences in depression-related behaviors in BDNF conditional knockout mice provide direct evidence for a role of BDNF in depression. The results also support the view that forebrain BDNF may be essential in mediating antidepressant efficacy.
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                Author and article information

                Contributors
                reut.avinun@mail.huji.ac.il
                ariel.knafo@huji.ac.il
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                04 April 2017
                May 2017
                : 7
                : 5 ( doiID: 10.1002/brb3.2017.7.issue-5 )
                : e00685
                Affiliations
                [ 1 ] Department of PsychologyThe Hebrew University of Jerusalem JerusalemIsrael
                Author notes
                [*] [* ] Correspondence

                Ariel Knafo‐Noam and Reut Avinun, Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem, 9190501 Israel.

                Emails: ariel.knafo@ 123456huji.ac.il and reut.avinun@ 123456mail.huji.ac.il

                Author information
                http://orcid.org/0000-0002-3281-1268
                http://orcid.org/0000-0003-0613-1960
                Article
                BRB3685
                10.1002/brb3.685
                5434190
                28523227
                b006acf3-db8c-4a83-b1c6-e415d6f15eb8
                © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 February 2017
                : 16 February 2017
                Page count
                Figures: 1, Tables: 2, Pages: 11, Words: 9085
                Funding
                Funded by: Israel Science Foundation
                Award ID: 31/06
                Funded by: European Research Council
                Award ID: 240994
                Funded by: Kaye Einstein Scholarship
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb3685
                May 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:17.05.2017

                Neurosciences
                fathers,gene–environment interaction,parenting,prosocial behavior,the brain‐derived neurotrophic factor gene,warmth

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