Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample

Peyrot, Wouter J.; Middeldorp, Christel M.; Jansen, Ritsert C.; Smit, Johannes H.; Geus, Eco J. C. de; Hottenga, Jouke‐Jan; Willemsen, Gonneke; Vink, Jacqueline M.; Virding, Susanne; Barragán, Isabel; Ingelman‐Sundberg, Magnus; Sim, Sarah C.; Boomsma, Dorret I.; Penninx, Brenda W. J. H.

doi:10.1016/j.jad.2012.08.044

Cited by 28 publications

(22 citation statements)

References 37 publications

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“…However, polymorphisms in the regulatory regions of MAOA, which negatively influence its transcriptional levels (Sabol et al, 1998), are also associated with enhanced anxiety and depressive behavior (Schmidt et al, 2000;Tadic et al, 2003). Likewise, the hypomorphic short (s) allelic variant of the 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with trait anxiety and 'neuroticism', and increased susceptibility to environmental stress in some (Grabe et al, 2012;Lesch et al, 1996;Xie et al, 2009), albeit not all studies (Fisher et al, 2012;Peyrot et al, 2013). These surprising associations are in line with reduced expression of 5-HTT found in brains of depressed individuals and suicide victims (Underwood et al, 2012;Willeit et al, 2000).…”

Section: -Ht and Emotional And Cognitive Behaviormentioning

confidence: 99%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

142

125

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Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety-and depressionrelated behaviors, and (3) a dopamine-and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

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Section: -Ht and Emotional And Cognitive Behaviormentioning

confidence: 99%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

142

125

View full text Add to dashboard Cite

show abstract

“…Short allele carriers who also experienced childhood maltreatment and recent life events showed increased vulnerability to stress, increased severity of depression, and reported persistent MDD rather than single, time-limited episodes [7,8,19]. Depression severity is a well-known risk factor of unfavorable treatment response [6], and childhood maltreatment is one of the main environmental predictors of severe depression [20].…”

Section: Methodsmentioning

confidence: 99%

“…Nonetheless, rare genetic variants generally have a larger impact; so, this might give us hope to identify genetic variants with more impressing effects, although the current sample sizes of most studies are too small to detect them [6]. Furthermore, environmental factors such as childhood maltreatment and stressful life events in several studies showed independent effects on selective serotonin reuptake inhibitor (SSRI) response, and in some cases, also in significant interaction with genetic polymorphisms [7,8]. Although there are several genes showing consistent interaction with certain environmental factors in the development of depression, only a fraction of these interactions was tested in the case of antidepressant treatment (Table 1) [9].…”

Section: Introductionmentioning

confidence: 99%

Antidepressant treatment response is modulated by genetic and environmental factors and their interactions

et al. 2014

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Although there is a wide variety of antidepressants with different mechanisms of action available, the efficacy of treatment is not satisfactory. Genetic factors are presumed to play a role in differences in medication response; however, available evidence is controversial. Even genome-wide association studies failed to identify genes or regions which would consequently influence treatment response. We conducted a literature review in order to uncover possible mechanisms concealing the direct effects of genetic variants, focusing mainly on reports from large-scale studies including STAR*D or GENDEP. We observed that inclusion of environmental factors, gene-environment and gene-gene interactions in the model improves the probability of identifying genetic modulator effects of antidepressant response. It could be difficult to determine which allele of a polymorphism is the risk factor for poor treatment outcome because depending on the acting environmental factors different alleles could be advantageous to improve treatment response. Moreover, genetic variants tend to show better association with certain intermediate phenotypes linked to depression because these are more objective and detectable than traditional treatment outcomes. Thus, detailed modeling of environmental factors and their interactions with different genetic pathways could significantly improve our understanding of antidepressant efficacy. In addition, the complexity of depression itself demands a more comprehensive analysis of symptom trajectories if we are to extract useful information which could be used in the personalization of antidepressant treatment.

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“…The field of epigenetics has arisen as one of the most important scientific axis to understand developmental physiology and pathophysiology in all areas of medicine with a special impact on psychiatry, a field that has been historically dominated by obsolete biological models and theories [21]. Environmental factors such as childhood maltreatment and stressful life events in several studies showed independent effects of Specific Serotonergic Reuptake Inhibitors (SSRI's) response, and in some cases, also in significant interaction with genetic polymorphisms [22].…”

Section: Epigeneticsmentioning

confidence: 99%

Childhood Trauma and Major Mental Illness – Integration of Psychopharmacology with Psychological Treatments

Haliburn¹

2016

J Neuropsychopharmacol Mental Health

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Effective treatment of major mental illness in children, adolescents and adults poses a continuing challenge to psychiatry, and unaddressed childhood trauma plays an important role in this challenge. The aim of this communication is based on an earlier paper, is to highlight research that has been carried out on the relationship between childhood maltreatment and major mental illness, and the emphasis placed on treatment of mental illness almost exclusively with pharmacotherapy while paying lip-service to psychological therapies, including dynamic psychotherapy. This is in spite of the Adverse Childhood Experiences (ACE's) Studies of 1998 and 2010, which demonstrate links between childhood trauma and mental illness. I have chosen to use depression as an example because of its common occurrence, increasing morbidity and cost to services globally.

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Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample

Abstract: Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.

Cited by 28 publications

References 37 publications

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Antidepressant treatment response is modulated by genetic and environmental factors and their interactions

Childhood Trauma and Major Mental Illness – Integration of Psychopharmacology with Psychological Treatments

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