- HTR1B was repeatedly found to be involved in the regulation of impulsive-aggressive behavior.
- SNPs of the HTR1B gene have been associated with various impulsivity-related clinical features such as suicidal behavior, substance abuse, and ADHD.
- The regulation and growth of 5-HT neurons and 5-HT signaling is strongly regulated by BDNF.
- Results of the study support the hypothesis that this gene–gene interaction could play a role in the susceptibility to BPD.
- Consider whether the HTR1B × BDNF interaction modulates the risk of developing BPD symptoms as a function of life events (e.g., childhood trauma).

University of Minnesota - Twin Cities

- BDNF encodes a member of the nerve growth factor family of proteins, otherwise known as brain-derived neurotrophic factor.
- Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain.
   - Influences the growth, maturation (differentiation), and maintenance of these cells. 
- May play a role in the regulation of the stress response and in the biology of mood disorders.

BDNF Gene

Tadić, A., Elsäßer, A., Victor, A., von Cube, R., Başkaya, Ö., Wagner, S., Lieb, K., Höppner, W., & Dahmen, N. (2009). Association analysis of serotonin receptor 1B (HTR1B) and brain-derived neurotrophic factor gene polymorphisms in borderline personality disorder. Journal of Neural Transmission, 116, 1185–1188. https://doi.org/10.1007/s00702-009-0264-3

Association analysis of serotonin receptor 1B (HTR1B) and brain-derived neurotrophic factor gene polymorphisms in borderline personality disorder

HTR1B x BDNF Interaction

- SNP in the BDNF gene resulting in a valine (Val) to methionine (Met) substitution at codon 66 negatively influences activity-dependent release of the BDNF protein, playing an important role in neuroplasticity.
- Val66Met SNP reported to be associated with cognitive and emotional dysfunctions by modifying cerebral cortex excitability, gray matter structures, or white matter integrities.
- Met-allele carriers, in comparison to Val homozygotes, had gray matter volume deficits found in the temporal, frontal areas, and thalamus.
- White matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygous group.
- Increased susceptibility to brain disorders in Met-allele carriers may correlate to the limited stability in white matter structural connectivity.

Val66Met Polymorphism

- In the adult brain, BDNF is maintained at high levels of expression and regulates both excitatory and inhibitory synaptic transmission and activity-dependent plasticity.
- The expression of specific BDNF exons can be regulated by epigenetic mechanisms, suggesting that environmental experiences dynamically influence mature BDNFs.
- There are high levels of BDNF in the hippocampus, amygdala, cerebellum, and cerebral cortex.
- Regulation of BDNF modulated by neuronal activity, exercise, antidepressants, stress, and hormones.
- BDNF is synthesized as the precursor, proBDNF, and is stored in dendrites and axons; can undergo cleavage intra- or extracellularly to produce mature BDNF protein.

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