The Unexpected Effects of Beneficial and Adverse Social Experiences during Adolescence on Anxiety and Aggression and Their Modulation by Genotype

Abstract

Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during adolescence instead of experiencing throughout beneficial social conditions leads to reduced levels of anxiety-like behavior.

Impact of Life History on Fear Memory and Extinction

“…This result shows that limited adversity in later life can have a positive effect on state anxiety in comparison to both accumulating adversity and sheltering from all stressors. Thus, the experience of some adversity may promote the ability of an individual to better cope with future challenges (Dienstbier, 1989 ; Fontana and Rosenheck, 1998 ; Parker et al, 2004 , 2006 ; Seery et al, 2010 , 2013 ; Sachser et al, 2011 ; Meyer et al, 2016 ).…”

“…Results of numerous studies show that positive and especially negative experiences during distinct phases of life, ranging from the prenatal and early postnatal stage, through adolescence to adulthood, do have profound effects on the behavioral phenotype (prenatal phase: Cratty et al, 1995 ; Seckl, 2004 ; Kaiser and Sachser, 2005 ; early postnatal phase: Vallée et al, 1997 ; Caldji et al, 1998 ; Meaney, 2001 ; Gross and Hen, 2004 ; Heiming et al, 2009 ; Taylor, 2010 ; Eiland et al, 2012 ; Ricon et al, 2012 ; adolescence: Spear, 2000 ; Schmidt et al, 2007 ; McCormick et al, 2008 ; Sachser et al, 2011 , 2013 ; Chaby et al, 2015 ; Meyer et al, 2016 ; adulthood: Buwalda et al, 2005 ; Jansen et al, 2010 ). However, only little is known about a possible interplay between these developmental stages.…”

Psychosocial Factors and Hypertension

“…25 Stereotype threat may be indirectly related to hypertension through weight changes and modulation of neural hormonal system. 26,27 Finally, stereotype threat can lead affected persons to delay seeking needed medical care, and have poor adherence to recommended therapies and generally poor patient-provider relationships. 14 …”

Varying Social Experiences in Adulthood Do Not Differentially Affect Anxiety-Like Behavior But Stress Hormone Levels

“…Throughout this phase (PND 107–PND 114), subjects were housed in special custom-made cage systems that comprised an interaction cage (Makrolon type III, with bedding and enrichment; food and water ad libitum ), a refuge cage (Makrolon type II, with bedding and enrichment; food and water ad libitum ) and a water basin (Makrolon type II, filled with water to a height of app. 3 cm; Meyer et al, 2016 ; see Figure 2 ). The water basin was connected to the interaction cage as well as to the refuge cage via plastic tunnels.…”