TY  - JOUR
A1  - Kuhn, Manuel
A1  - Scharfenort, Robert
A1  - Schümann, Dirk
A1  - Schiele, Miriam A.
A1  - Münsterkötter, Anna L.
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - Haaker, Jan
A1  - Kalisch, Raffael
A1  - Pauli, Paul
A1  - Reif, Andreas
A1  - Romanos, Marcel
A1  - Zwanzger, Peter
A1  - Lonsdorf, Tina B.
T1  - Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament
JF  - Social Cognitive and Affective Neuroscience
N2  - Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.
KW  - VBM
KW  - childhood maltreatment
KW  - adversity
KW  - stressful life events
KW  - mismatch
KW  - allostatic load
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189645
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Spinelli, Simona
A1  - Müller, Tanja
A1  - Friedel, Miriam
A1  - Sigrist, Hannes
A1  - Lesch, Klaus-Peter
A1  - Henkelman, Mark
A1  - Rudin, Markus
A1  - Seifritz, Erich
A1  - Pryce, Christopher R.
T1  - Effects of repeated adolescent stress and serotonin transporter gene partial knockout in mice on behaviors and brain structures relevant to major depression
JF  - Frontiers in Behavioral Neuroscience
N2  - In humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype x developmental stress effect on brain structure and function is limited. Here, we investigated the effect of repeated stress exposure during adolescence in mice with partial knockout of the 5-HIT gene (HET) vs. wildtype (WT) on early-adulthood behavioral measures and brain structure [using magnetic resonance imaging (MRI)] relevant to human major depression. Behaviorally, adolescent stress (AS) increased anxiety and decreased activity and did so to a similar degree in HET and WT. In a probabilistic reversal learning task, HET-AS mice achieved fewer reversals than did HET-No-AS mice. 5-HIT genotype and AS were without effect on corticosterone stress response. In terms of structural brain differences, AS reduced the volume of two long-range white matter tracts, the optic tract (OT) and the cerebral peduncle (CP), in WT mice specifically. In a region-of-interest analysis, AS was associated with increased HC volume and HET genotype with a decreased frontal lobe volume. In conclusion, we found that 5-HIT and AS genotype exerted long-term effects on behavior and development of brain regions relevant to human depression.
KW  - mouse-brain
KW  - white-matter integrity
KW  - linked polymorphic region
KW  - C57BL/6 mice
KW  - lerned helplessness
KW  - 5-HTTLPR polymorphism
KW  - childhood maltreatment
KW  - rhesus macaques
KW  - 3-dimensional MRI
KW  - life stress
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122240
VL  - 7
ER  -