TY - JOUR
T1 - Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder
T2 - Focus on Treatment Outcomes in an Asiatic Sample
AU - Calabrò, Marco
AU - Mandelli, Laura
AU - Crisafulli, Concetta
AU - Lee, Soo Jung
AU - Jun, Tae Youn
AU - Wang, Sheng Min
AU - Patkar, Ashwin A.
AU - Masand, Prakash S.
AU - Benedetti, Francesco
AU - Han, Changsu
AU - Pae, Chi Un
AU - Serretti, Alessandro
N1 - Funding Information:
Funding. This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (grant number: HC15C1405), no funding or sponsorship was received for this study or publication of this article.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Introduction: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. Methods: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6–8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. Results: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. Discussion: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.
AB - Introduction: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. Methods: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6–8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. Results: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. Discussion: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.
KW - BDNF
KW - Bipolar disorder
KW - CHL1
KW - HOMER1
KW - HTR2A
KW - Major depression
KW - Neuroplasticity
KW - Neurotransmission
KW - RORA
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=85053412969&partnerID=8YFLogxK
U2 - 10.1007/s12325-018-0781-2
DO - 10.1007/s12325-018-0781-2
M3 - Article
C2 - 30178121
AN - SCOPUS:85053412969
SN - 0741-238X
VL - 35
SP - 1656
EP - 1670
JO - Advances in Therapy
JF - Advances in Therapy
IS - 10
ER -
