TY - JOUR
T1 - Convergent neurobiological predictors of mood and anxiety symptoms and treatment response
AU - Jabbi, Mbemba
AU - Nemeroff, Charles B.
N1 - Funding Information:
M Jabbi is supported by the University of Texas Dell Medical School; CB Nemeroff is supported by the University of Texas Dell Medical School; National Institutes of Health (NIH) and the Stanley Medical Research Institute Authors would like to thank Christine Thomas for providing picture contents for figures 1 & 2, and Wade Weber for edits of an earlier version of the manuscript.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Introduction: Mood and anxiety disorders are leading contributors to the global burden of diseases. Comorbid mood and anxiety disorders have a lifetime prevalence of ~20% globally and increases the risk for suicide, a leading cause of death. Areas covered: In this review, authors highlight recent advances in the understanding of multilevel-neurobiological mechanisms for normal/pathological human affective-functioning. The authors then address the complex interplay between environmental-adversity and molecular-genetic mediators of brain correlates of affective-symptoms. The molecular focus is strategically limited to GTF2i, BDNF, and FKBP5 genes that are, respectively, involved in transcriptional-, neurodevelopmental- and neuroendocrine-pathway mediation of affective-functions. The importance of these genes is illustrated with studies of copy-number-variants, genome-wide association (GWAS), and candidate gene-sequence variant associations with disease etiology. Authors concluded by highlighting the predictive values of integrative neurobiological processing of gene–environment interactions for affective disorder symptom management. Expert opinion: Given the transcriptional, neurodevelopmental and neuroimmune relevance of GTF2i, BDNF, and FKBP5 genes, respectively, authors reviewed the putative roles of these genes in neurobiological mediation of adaptive affective-responses. Authors discussed the importance of studying gene-dosage effects in understanding affective disorder risk biology, and how such targeted neurogenetic studies could guide precision identification of novel pharmacotherapeutic targets and aid in prediction of treatment response.
AB - Introduction: Mood and anxiety disorders are leading contributors to the global burden of diseases. Comorbid mood and anxiety disorders have a lifetime prevalence of ~20% globally and increases the risk for suicide, a leading cause of death. Areas covered: In this review, authors highlight recent advances in the understanding of multilevel-neurobiological mechanisms for normal/pathological human affective-functioning. The authors then address the complex interplay between environmental-adversity and molecular-genetic mediators of brain correlates of affective-symptoms. The molecular focus is strategically limited to GTF2i, BDNF, and FKBP5 genes that are, respectively, involved in transcriptional-, neurodevelopmental- and neuroendocrine-pathway mediation of affective-functions. The importance of these genes is illustrated with studies of copy-number-variants, genome-wide association (GWAS), and candidate gene-sequence variant associations with disease etiology. Authors concluded by highlighting the predictive values of integrative neurobiological processing of gene–environment interactions for affective disorder symptom management. Expert opinion: Given the transcriptional, neurodevelopmental and neuroimmune relevance of GTF2i, BDNF, and FKBP5 genes, respectively, authors reviewed the putative roles of these genes in neurobiological mediation of adaptive affective-responses. Authors discussed the importance of studying gene-dosage effects in understanding affective disorder risk biology, and how such targeted neurogenetic studies could guide precision identification of novel pharmacotherapeutic targets and aid in prediction of treatment response.
KW - Affect
KW - anxiety
KW - brain
KW - depression
KW - environment
KW - function
KW - genetics
KW - prediction
KW - structure
KW - treatment
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U2 - 10.1080/14737175.2019.1620604
DO - 10.1080/14737175.2019.1620604
M3 - Review article
C2 - 31096806
AN - SCOPUS:85067183753
VL - 19
SP - 587
EP - 597
JO - Expert Review of Neurotherapeutics
JF - Expert Review of Neurotherapeutics
SN - 1473-7175
IS - 6
ER -