Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder

Abstract

Background Physical or psychological adversity in childhood is associated with a higher risk for depression in adulthood, and with persistent serotonergic abnormalities in humans and in animal models. We hypothesized that reported childhood abuse would be associated with lower brain serotonin transporter (5-HTT) binding potential (BPP, proportional to the number of available transporters) in adults. We examined healthy volunteers and subjects with major depressive disorder, a sample enriched for childhood abuse. Methods Regional brain 5-HTT BPP was measured using positron emission tomography with [11C]McN 5652 and a metabolite corrected arterial input function in 43 healthy volunteers and 23 subjects in a major depressive episode, ten of whom reported a history of sexual and/or physical abuse before age 15, and 13 of whom did not. As only two healthy volunteers reported childhood abuse, primary analyses were restricted to the depressed sample, with healthy controls presented as comparators. Results Depressed subjects reporting childhood abuse had lower 5-HTT BPP than non-abused depressed subjects across all brain regions examined (p=0.017). The groups did not differ in relevant demographic or clinical variables. Genotype frequencies of a functional polymorphism in the 5-HTT gene promoter (5-HTTLPR) did not differ between the groups. Conclusions Reported childhood abuse is associated with lower 5-HTT BPP in this sample of subjects with major depression, consistent with other reports that childhood adversity can lower serotonergic function permanently. Lower 5-HTT BPP may represent a biological pathway through which early life stress predisposes to the development of subsequent psychiatric illness, including major depressive disorder.

Molecular Brain Imaging of Personality Traits in Nonhuman Primates: A Study of the Common Marmoset

“…Although recent methodological developments have permitted the use of experimental animals for in vivo brain imaging, few studies have examined the behavioral personality traits of nonhuman primates (Morgan et al 2002;Heinz et al 2003;Ichise et al 2006). Using a specific tracer for SERT, PET studies with macaque monkeys have revealed that regional abnormalities in brain serotonergic systems may be related to behavioral abnormalities caused by early life stress Wrase et al 2006), which is similar to that observed in a human PET study (Miller et al 2009). PET imaging studies with human and nonhuman primates have thus acted as a bridge between basic and clinical research.…”

“…Similarly, the effects of childhood adversity on SERT binding were confirmed in a human PET study using patients with major depression (Miller et al 2009). …”

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

“…Moreover, there are several aspects other than genetic ones that have been shown to influence or associate with serotonin transporter binding. These include ethnicity (Praschak-Rieder et al, 2007), personality (Kalbitzer et al, 2009), biography (Miller et al, 2009) and psychiatric diagnoses (Malison et al, 1998;Meyer et al, 2004;Selvaraj et al, 2009; for review see Meyer, 2007;Stockmeier, 2003), and, as recently shown, time of the year when scanning takes place. Using [ 11 C]DASB and PET, we were able to show that serotonin transporter binding varies across seasons, with highest binding measured in fall and winter, and lower binding measured in spring and summer, with peak differences being as high as 40% (Praschak-Rieder et al, 2008).…”

Brain Serotonin Transporter Occupancy by Oral Sibutramine Dosed to Steady State: A PET Study Using 11C-DASB in Healthy Humans

“…For example, a common triallelic polymorphism at the serotonin transporter-linked polymorphic region (5-HTTLPR) on chromosome 17q12 impacts on SERT mRNA transcription and confers variability in SERT expression that is measurable by 11 C-DASB PET (Praschak-Rieder et al, 2007;Reimold et al, 2007). Environmental factors include seasonal variation in SERT availability (Praschak-Rieder et al, 2008) and evidence that childhood adversity may be associated with a persisting reduction of SERT availability in adulthood (Miller et al, 2009). A recent PET study has found low SERT to be associated with poor treatment response to other drugs (antidepressants) acting largely via monoamine reuptake inhibition (Miller et al, 2008).…”