Linkage Disequilibrium of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism in Children With a Prepubertal and Early Adolescent Bipolar Disorder Phenotype

University of Chicago, Chicago, Illinois, United States
American Journal of Psychiatry (Impact Factor: 12.3). 10/2004; 161(9):1698-700. DOI: 10.1176/appi.ajp.161.9.1698
Source: PubMed


Transmission of the brain-derived neurotrophic factor (BDNF) Val66 allele in children with a prepubertal and early adolescent bipolar disorder phenotype was examined.
The prepubertal and early adolescent bipolar disorder phenotype was defined as current DSM-IV bipolar I disorder (manic or mixed phase) with at least one cardinal mania criterion (i.e., euphoria and/or grandiosity) to ensure differentiation from attention deficit hyperactivity disorder. Probands (mean age=10.7 years, SD=2.7) were obtained by consecutive new case ascertainment from designated pediatric and psychiatric venues. Parents and probands were interviewed separately by research nurses who were blind to the probands' diagnoses. Genotyping was done with TaqMan Assay-on-Demand. Analysis was done with the Family Based Association Test program.
There were 53 complete, independent trios. The BDNF Val66 allele was preferentially transmitted (Family Based Association Test: chi(2)=6.0, df=1, p=0.014).
This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele.

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Available from: Rebecca Tillman, Jan 30, 2015
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    • "Disturbances in this relationship have been associated with increased risk for a number of mental disorders and neurobiological dysfunctions (Enns et al., 2002; Klier and Muzik, 2004; Tyrka et al., 2008). For instance, low maternal warmth is one of the leading risk factors associated with the risk of mania relapse after recovery in child BD subjects (Geller et al., 2008, 2004). "
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    • "Haploinsufficiency Increased aggressiveness and hyperphagia (Lyons et al., 1999) V66M (heterozygous knockin) Increased immobility in forced swim test and decreased sucrose intake after stress (depressive endophenotype) (Yu et al., 2012) V66M (homozygous knockin) Decreased hippocampal volume, decreased hippocampal dendritic complexity, increased anxietyrelated behaviors (Chen et al., 2006b), decreased volume and dendritic complexity in vmPFC with impaired extinction learning (Yu et al., 2009), decreased spine density and diameter in PFC (Liu et al., 2012) Val66 (most common allele in general population) Bipolar disorder (Geller et al., 2004) V66M Depression (Schumacher et al., 2005), bipolar disorder (Neves-Pereira et al., 2002), episodic memory deficit in both homozygous and heterozygous people (Egan et al., 2003), childhood onset OCD (Hall et al., 2003), eating disorders (Ribases et al., 2003, 2004), schizophrenia (Neves-Pereira et al., 2005) "
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    • ") and develop depression, mood and anxiety disorders (Hall et al., 2003; Geller et al., 2004; Strauss et al., 2005; Hilt et al., 2007). In contrast, studies on adult depression have found that Met allele carriers are over-represented in clinical populations (Jiang et al., 2005; Hilt et al., 2007) or exhibit higher rumination or depressive symptoms in community samples (Beevers et al., 2009; Duncan et al., 2009), but see also Juhasz et al. (2011). "
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