Individual and Combined Effect of / Gene Variants and Adverse Childhood Experiences on the Severity of Major Depressive Disorder

Overview

Journal Behav Sci (Basel)

Date 2023 Oct 27

PMID 37887445

Authors

Christian Gabriel Toledo-Lozano

Luz Berenice Lopez-Hernandez

Juan Antonio Suarez-Cuenca

Luis Villalobos-Gallegos

Dulce Adei Jimenez-Hernandez

Sofia Lizeth Alcaraz-Estrada

Paul Mondragon-Teran

Lilia Joya-Laureano

Ramon Mauricio Coral-Vazquez

Silvia Garcia

Affiliations

Soon will be listed here.

Abstract

Background: Major depressive disorder (MDD) is a mood disorder with a high prevalence worldwide that causes disability and, in some cases, suicide. Although environmental factors play a crucial role in this disease, other biological factors may predispose individuals to MDD. Genetic and environmental factors influence mental disorders; therefore, a potential combined effect of / gene variants may be a target for the study of susceptibility to MDD. This study aimed to evaluate the effects of and gene variants when combined with adverse childhood experiences (ACEs) on the susceptibility and severity of symptoms in MDD.

Methods: A case-control study was performed, including 345 individuals, 175 MDD cases and 170 controls. Genotyping was performed using real-time PCR with hydrolysis probes. The analysis of the and gene variants of and , respectively, was performed either alone or in combination with ACEs on the severity of depression, as determined through specific questionnaires, including DSM-IV diagnostic criteria for MDD.

Results: According to individual effects, the presence of ACEs, as well as the allele G of the rs1465107 of , is associated with a higher severity of depression, more significantly in females. Furthermore, the allele G of was associated with the severity of depression, even after being adjusted by gene variants and ACEs (IRR = 1.67, = 0.01). In males, the allele G of was shown to interact with SNP with ACEs (IRR = 1.70, < 0.001). According to combined effect analyses, the severity of depression was associated with ACEs when combined with either allele of or allele of , whereas SNP risk association was influenced by gender.

Conclusions: The severity of depression is related to either individual or combined effects of temperamental traits and genetic susceptibility of specific genes such as and .

References

Lung F, Tzeng D, Huang M, Lee M . Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder. BMC Med Genet. 2011; 12:74. PMC: 3127823. DOI: 10.1186/1471-2350-12-74. View

Zhang J, Chen Y, Zhang K, Yang H, Sun Y, Fang Y . A cis-phase interaction study of genetic variants within the MAOA gene in major depressive disorder. Biol Psychiatry. 2010; 68(9):795-800. DOI: 10.1016/j.biopsych.2010.06.004. View

Cicchetti D, Rogosch F, Sturge-Apple M . Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: depressive symptomatology among adolescents from low socioeconomic status backgrounds. Dev Psychopathol. 2007; 19(4):1161-80. DOI: 10.1017/S0954579407000600. View

Li X, Mu F, Liu D, Zhu J, Yue S, Liu M . Predictors of suicidal ideation, suicide attempt and suicide death among people with major depressive disorder: A systematic review and meta-analysis of cohort studies. J Affect Disord. 2022; 302:332-351. DOI: 10.1016/j.jad.2022.01.103. View

Ochi T, Vyalova N, Losenkov I, Paderina D, Pozhidaev I, Loonen A . Limited Associations Between 5-HT Receptor Gene Polymorphisms and Treatment Response in Antidepressant Treatment-Free Patients With Depression. Front Pharmacol. 2020; 10:1462. PMC: 6951408. DOI: 10.3389/fphar.2019.01462. View

Benjet C . Childhood adversities of populations living in low-income countries: prevalence, characteristics, and mental health consequences. Curr Opin Psychiatry. 2010; 23(4):356-62. DOI: 10.1097/YCO.0b013e32833ad79b. View

Fergusson D, Boden J, Horwood L, Miller A, Kennedy M . Moderating role of the MAOA genotype in antisocial behaviour. Br J Psychiatry. 2012; 200(2):116-23. PMC: 3269651. DOI: 10.1192/bjp.bp.111.093328. View

Ramesh V, Venkatesan V, Ramasamy B . Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder. Hum Psychopharmacol. 2022; 37(4):e2830. DOI: 10.1002/hup.2830. View

Naoi M, Maruyama W, Shamoto-Nagai M . Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis. J Neural Transm (Vienna). 2017; 125(1):53-66. DOI: 10.1007/s00702-017-1709-8. View

10.

Naoi M, Riederer P, Maruyama W . Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression. J Neural Transm (Vienna). 2015; 123(2):91-106. DOI: 10.1007/s00702-014-1362-4. View

11.

Spies M, Murgas M, Vraka C, Philippe C, Gryglewski G, Nics L . Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo. Transl Psychiatry. 2023; 13(1):208. PMC: 10272199. DOI: 10.1038/s41398-023-02506-2. View

12.

Beach S, Brody G, Gunter T, Packer H, Wernett P, Philibert R . Child maltreatment moderates the association of MAOA with symptoms of depression and antisocial personality disorder. J Fam Psychol. 2010; 24(1):12-20. PMC: 2839928. DOI: 10.1037/a0018074. View

13.

Cruz-Fuentes C, Benjet C, Martinez-Levy G, Perez-Molina A, Briones-Velasco M, Suarez-Gonzalez J . BDNF Met66 modulates the cumulative effect of psychosocial childhood adversities on major depression in adolescents. Brain Behav. 2014; 4(2):290-7. PMC: 3967543. DOI: 10.1002/brb3.220. View

14.

Green J, McLaughlin K, Berglund P, Gruber M, Sampson N, Zaslavsky A . Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010; 67(2):113-23. PMC: 2822662. DOI: 10.1001/archgenpsychiatry.2009.186. View

15.

Diaz-Marsa M, Carrasco J, Hollander E, Cesar J, Saiz-Ruiz J . Decreased platelet monoamine oxidase activity in female anorexia nervosa. Acta Psychiatr Scand. 2000; 101(3):226-30. View

16.

Khan A, McCormack H, Bolger E, McGreenery C, Vitaliano G, Polcari A . Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males and Females. Front Psychiatry. 2015; 6:42. PMC: 4378368. DOI: 10.3389/fpsyt.2015.00042. View

17.

Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P . A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991; 11(3):298-300, 302. View

18.

Konjevod M, Sreter K, Popovic-Grle S, Lampalo M, Tudor L, Jukic I . Platelet Serotonin (5-HT) Concentration, Platelet Monoamine Oxidase B (MAO-B) Activity and , , and Gene Polymorphisms in Asthma. Biomolecules. 2023; 13(5). PMC: 10216077. DOI: 10.3390/biom13050800. View

19.

Chiesa A, Lia L, Alberti S, Lee S, Han C, Patkar A . Lack of influence of rs4680 (COMT) and rs6276 (DRD2) on diagnosis and clinical outcomes in patients with major depression. Int J Psychiatry Clin Pract. 2014; 18(2):97-102. DOI: 10.3109/13651501.2014.894073. View

20.

Bortolato M, Shih J . Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. Int Rev Neurobiol. 2011; 100:13-42. PMC: 3371272. DOI: 10.1016/B978-0-12-386467-3.00002-9. View