Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum

Abstract

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.child abuse | physical abuse | sexual abuse | allostatic load

Hippocampal Atrophy in Major Depression: a Function of Childhood Maltreatment Rather than Diagnosis?

“…Remarkably, this negative correlation remained significant even when accounting for group membership as a control variable in the whole-sample analysis, as it is also found in both groups separately. This is again well in line with previous reports demonstrating strong maltreatment effects on hippocampal volumes even if MDD patient status or life-time presence of affective disorders is accounted for (Chaney et al, 2014;Teicher et al, 2012).…”

“…First, our finding of reduced hippocampal volumes in depressed patients compared with healthy controls is well in line with numerous imaging studies showing similar effects, including meta-analyses (Arnone et al, 2012a;Cole et al, 2011;MacQueen and Frodl, 2011). Second, the results of our study suggest a strong impact of childhood maltreatment on hippocampal morphometry in both, patients and healthy subjects, with comparable effect sizes in both samples (accounting for B8-9% variance of hippocampal volume), which is also in accordance with several previous studies reporting similar effects and effect sizes (Dannlowski et al, 2012;Edmiston et al, 2011;Teicher et al, 2012) but contradicts a study by Lenze et al (2008) that found childhood adversity to be associated with earlier onset of MDD but not with reduced hippocampal volume.…”

“…There has been growing evidence regarding the genesis of these trauma-related changes in limbic structures to be independent from disease status, as they could be found in both healthy subjects and currently depressed patients suffering from MDD (Chaney et al, 2014;Edmiston et al, 2011;Frodl et al, 2010b;Vythilingam et al, 2002). Teicher et al (2012) showed that hippocampal shape alterations in subjects having experienced childhood maltreatment is not mediated by the presence or absence of life-time affective disorders.…”

Amygdala–Hippocampal Connectivity Changes During Acute Psychosocial Stress: Joint Effect of Early Life Stress and Oxytocin

“…Stress-induced FC changes were calculated as the differences in FC strength between the stress and control conditions. Previous studies have associated ELS with reduced gray matter volume (GMV) in limbic areas (Teicher et al, 2012) and with personality traits, such as neuroticism, trait anxiety, and selfesteem (Grimm et al, 2014). We further explored the influence of GMV and personality traits on the main effect of EA, using ROI-based multiple regression model (main predictor: EA; covariates: age, IQ, experimental sequence, GMV in seed region, GMV in the corresponding ROI, neuroticism, trait anxiety, and self-esteem).…”

Trauma is a public health issue

“…Exposure to trauma is particularly detrimental when it occurs in childhood or adolescence, disrupting numerous aspects of development in cognitive, emotional, and social domains, leading to adverse mental health and educational outcomes (Cicchetti & Toth, 1995; Koenen, Moffit, Caspi, Taylor, & Purcell, 2003) with long-term consequences for learning and memory (Teicher, Anderson, & Polcari, 2012), emotional functioning (De Bellis et al, 1994; McCrory et al, 2011; McLaughlin & Hatzenbuehler, 2009; Pollak & Sinha, 2002; Pollak, Vardi, Putzer Bechner, & Curtin, 2005), social relationships, elevated risk of re-victimization (Cole & Putnam, 1992; DiLillo, 2001; Follette, Polusney, Bechtle, & Naugle, 1996), and mental disorders (Kilpatrick et al, 2003; McLaughlin et al, 2012, 2013). …”