The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults

Kilpatrick, Dean G.; Koenen, Karestan C.; Ruggiero, Kenneth J.; Acierno, Ron; Galea, Sandro; Resnick, Heidi S.; Roitzsch, John C.; Boyle, John; Gelernter, Joel

doi:10.1176/appi.ajp.2007.06122007

Cited by 364 publications

(296 citation statements)

References 39 publications

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“…These include polymorphisms or expression of BDNF (Krishnan et al, 2007), GABRA2 (Nelson et al, 2009), 5-HT1A receptors, dopamine or serotonin transporters (Segman et al, 2002;Kilpatrick et al, 2007;Stein et al, 2009;Wald et al, 2013), catechol-O-methyl transferase (COMT; Jabbi et al, 2007;Kolassa et al, 2010), glucocorticoid receptors and factors that modulate them such as FK506-binding protein (FKBP5;Binder et al, 2008;Derijk and de Kloet, 2008;McGowan et al, 2009;Sarapas et al, 2011), and methylation of corticotrophin-releasing factor (CRF) receptor DNA (Elliott et al, 2010). Several genetically distinct rodent lines are differentially resistant/vulnerable to the effects of stress (Razzoli et al, 2011;Savignac et al, 2011;Camp et al, 2012;Fuchsl et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Hetzel

Rosenkranz

2014

Neuropsychopharmacol

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Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that contribute to resilience to the effects of stress.

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Section: Discussionmentioning

confidence: 99%

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Hetzel

Rosenkranz

2014

Neuropsychopharmacol

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“…In addition, studies have begun to investigate the offspring methylation status and gene variants of SLC6A4, the serotonin transporter gene, and an association with intergenerational stress, as SLC6A4 has been shown to moderate risk for psychopathology in the face of environmental stressors (Taylor et al, 2006;Kilpatrick et al, 2007;Grabe et al, 2009;Xie et al, 2009). Offspring born to mothers with at least one major stressful/traumatic life event during pregnancy have lower serotonin transporter mRNA levels compared with those without maternal prenatal stress.…”

Section: Epigeneticsmentioning

confidence: 99%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

381

269

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The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as 'intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress-or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field.

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“…15 Although interviews are preferable to unaided self-report, they are still based on verbal report and memory of research participants, and therefore are unlikely to be immune to subjective influences. Therefore, we separately 16 Otte et al 18 Kohen et al 17 Nobile et al although no test of gene-environment interaction was reported in the available publications. Full references to all studies are included in Supplementary Information.…”

Section: Review Of Published Literaturementioning

confidence: 99%

“…A major advance in the literature over the last 5 years has been a proliferation of studies where environmental adversity is objectively ascertained, including a natural catastrophe 16 or objectively diagnosed physical illness. 17,18 These studies assess a narrow range of exposures compared with questionnaires and interviews, but are valuable as subjective factors in the report of adversity are excluded and geneenvironment correlation is unlikely to be involved.…”

Section: Contribution Of Objective and Experimental Studiesmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

2009

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An updated review of 34 human observational studies indicates that the length polymorphism of the serotonin transporter gene moderates the effect of environmental adversity in the development of depression. This finding depends on the use of contextual or objective methods to assess environmental adversity and is attenuated when self-report instruments are used. Inconsistent findings in male adolescents suggest a developmental stage and sex-specific protective mechanism. These systematic relationships between method and results should be followed up to specify causal mechanisms leading to depression.

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The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults

Abstract: The low-expression variant of the 5-HTTLPR polymorphism modifies risk of postdisaster PTSD and major depression under conditions of high hurricane exposure and low social support, confirming and extending previous research.

Cited by 364 publications

References 39 publications

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Intergenerational Transmission of Stress in Humans

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

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