White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms

Tatham, Erica L.; Ramasubbu, Rajamannar; Gaxiola‐Valdez, Ismael; Cortese, Filomeno; Clark, Darren L.; Goodyear, Bradley G.; Foster, Jane A.; Hall, Geoffrey B.

doi:10.1016/j.pscychresns.2016.04.014

Cited by 37 publications

(33 citation statements)

References 77 publications

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“…In the current study, we tried to extend prior findings by relating different kinds of CA to white matter differences. Surprisingly, but in line with a recent study by Tatham and colleagues (Tatham et al, ), only increased scores on the PN subscale were associated with decreased connectivity in a broad set of brain tracts associated with emotional appraisal and regulation. Neglect is the failure to provide for the shelter, safety, supervision and nutritional needs of the child (English, Thompson, Graham, & Briggs, ).…”

Section: Discussionsupporting

confidence: 87%

Physical neglect during childhood alters white matter connectivity in healthy young males

Tendolkar

Mårtensson

Kühn

et al. 2017

Human Brain Mapping

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PN may have severe consequences and should be considered equally important to more active forms of abuse. FA changes, particularly in the cingulum, actually appear to a functional consequence and are linked to trait anxiety, a personality dimension that is suggested to be a transdiagnostic risk factor of affective disorders. Potentially this reveals a mechanistic chain that forms one pathyway from CA to disease.

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Section: Discussionsupporting

confidence: 87%

Physical neglect during childhood alters white matter connectivity in healthy young males

Tendolkar

Mårtensson

Kühn

et al. 2017

Human Brain Mapping

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“…It is also conceivable that the association between structural coupling and genetic variations is more pronounced in interaction with stressful conditions, like the development of psychiatric disorders or stressful life events. In line with this notion, a series of studies found no main effects but (only) interaction effects between FA-values and 5-HTTLPR on specific psychiatric symptoms and treatment responses for different tracts and psychiatric disorders (Tatham et al, 2016 , 2017 ). In congruence with this, Kelly et al ( 2014 ) also observed similar findings for further genotypes by showing no association between specific different genetic variations (e.g., for schizophrenia) and white matter alterations in healthy subjects, which already has been confirmed in meta-analyses for patients (Ellison-Wright and Bullmore, 2009 ).…”

Section: Discussionmentioning

confidence: 90%

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531)

Klucken

León

Blecker³

et al. 2018

Front. Behav. Neurosci.

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Recent work underlines the importance of alterations in white matter (e.g., measured by fractional anisotropy (FA)) as a neural vulnerability marker for psychiatric disorders. In this context, the uncinate fasciculus (UF), which connects the limbic system with prefrontal areas, has repeatedly been linked to psychiatric disorders, fear processing, and anxiety-related traits. Individual differences in FA may partly be genetically determined. Variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) is a particularly promising candidate in this context, which has been linked to psychiatric disorders as well as to limbic and prefrontal reactivity. However, findings on the association between the 5-HTTLPR and FA within the UF-tract have been heterogeneous. The present study investigated this relationship and extended previous work by considering different genetic classification approaches as well as sex effects in a human sample (n = 114). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. As a main result, we did not find any significant relationship between the 5-HTTLPR and FA in the UF-tract although power analyses showed an adequate power. In addition, genotype effects were neither found when different classification approaches were used nor when analyses were carried out in males or females only. The present findings suggest that the association of the 5-HTTLPR and FA seems to be a more labile phenomenon than previously assumed. Possible explanations and limitations are discussed.

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“…Both depression and the Met allele of the Val66Met polymorphism on the gene coding for BDNF may be accompanied by reductions in structural and functional connectivity of the hippocampus and prefrontal cortex (Frodl et al, 2007; Molendijk et al, 2012; Kim et al, 2013; Ziegler et al, 2013; Tatham et al, 2016), and BDNF concentrations in serum have been linked to depressive disorders (Shimizu et al, 2003; Wolkowitz et al, 2011; Bus et al, 2015). However, as evidence for a direct relationship between BDNF genotype and depression has not been consistently observed (Verhagen et al, 2010), it was of interest to examine whether the Met polymorphism on the BDNF gene would be associated with cognitive processes that might confer greater vulnerability to depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…As the Met allele of the Val66Met gene may also be associated with structural and functional changes of prefrontal cortical areas (Liu et al, 2012; Kim et al, 2013), as well as decreased white matter integrity in frontal lobe tracts (Ziegler et al, 2013; Tatham et al, 2016), it might be reasonable to expect that the BDNF genotype would moderate the relations between loneliness, self-efficacy, and depression. This said, because BDNF may serve as a neuroplasticity factor, it could be argued that the influence of BDNF in relation to depressive symptoms could vary with situational influences, as has previously been shown with relations involving serotonin (Belsky et al, 2007, 2009).…”

Section: Introductionmentioning

confidence: 99%

Loneliness in Relation to Depression: The Moderating Influence of a Polymorphism of the Brain Derived Neurotrophic Factor Gene on Self-efficacy and Coping Strategies

et al. 2017

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Disturbances of brain derived neurotrophic factor (BDNF) signaling, which may occur among those with a polymorphism of the Val66Met gene, comprising a Met substitution for the Val allele, may be associated with depressive cognitions. However, presumed elevated BDNF levels among individuals with the Val/Val genotype, might confer increased responsivity to contextual challenges, thus fostering vulnerability to depression. In Study 1, among undergraduate students (N = 252), increased loneliness perceptions were accompanied with depressive symptoms. This relationship was moderated by self-efficacy and BDNF genotype, such that when individuals appraised high self-efficacy, those with the Val/Val genotype, compared to Met carriers, reported greater depression scores when they perceived feeling lonely. Study 2 revealed that among undergraduate students (N = 178), lower depressive scores were associated with increased problem-focused coping among Val/Val individuals, but not Met carriers. Moreover, with increased perceived loneliness, Val/Val carriers endorsed lower problem-focused coping. Findings suggest that Val/Val individuals may have adverse neurocognitive vulnerability to loneliness experiences.

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White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms

Cited by 37 publications

References 77 publications

Physical neglect during childhood alters white matter connectivity in healthy young males

Physical neglect during childhood alters white matter connectivity in healthy young males

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531)

Loneliness in Relation to Depression: The Moderating Influence of a Polymorphism of the Brain Derived Neurotrophic Factor Gene on Self-efficacy and Coping Strategies

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