The interaction between <i>AVPR1A</i> RS3 and 3-level childhood adversity on the availability to social interaction.

<p>The interaction between <i>AVPR1A</i> RS3 and 3-level childhood adversity [CA, no, mild-moderate, severe] on availability to social integration (AVSI) [a] and on availability to attachment (AVAT), in males [b] and females [c]). Dots indicate estimated marginal means and error bars represent one standard error of the mean. Open diamonds represent those homozygous for the long (L) allele group, filled squares represent the carriers of at least one short (S) allele. Statistical significance between genotypes in specific childhood adversity group, as well as statistical significance of the <i>AVPR1A</i> * CA interaction (GXE) are indicated: * <i>P</i><0.05, ** <i>P</i><0.005.</p

The interaction between <i>AVPR1A</i> RS3 and 2-level childhood adversity on the availability to social interaction.

<p>The interaction between <i>AVPR1A</i> RS3 and 2-level childhood adversity [CA, no or yes] on availability to social integration (AVSI) [a] and on availability to attachment (AVAT), in males [b] and females [c]). Dots indicate estimated marginal means and error bars represent one standard error of the mean. Open diamonds represent those homozygous for the long (L) allele group, filled squares represent the carriers of at least one short (S) allele. Statistical significance between genotypes in each childhood adversity group, as well as statistical significance of the <i>AVPR1A</i> * CA interaction (GXE) are indicated. * <i>P</i><0.05, ** <i>P</i><0.005.</p

Allele frequency distribution of <i>AVPR1A</i> RS3.

<p>Allele frequency distribution of <i>AVPR1A</i> RS3.</p

Impact of Childhood Adversity and <i>Vasopressin receptor 1a</i> Variation on Social Interaction in Adulthood: A Cross-Sectional Study

<div><p>Background</p><p>Arginine vasopressin (AVP) plays a role in social behavior, through receptor AVPR1A. The promoter polymorphism <i>AVPR1A</i> RS3 has been associated with human social behaviors, and with acute response to stress. Here, the relationships between <i>AVPR1A</i> RS3, early-life stressors, and social interaction in adulthood were explored.</p><p>Methods</p><p>Adult individuals from a Swedish population-based cohort (<i>n</i> = 1871) were assessed for self-reported availability of social integration and social attachment and for experience of childhood adversities. Their DNA samples were genotyped for the microsatellite <i>AVPR1A</i> RS3.</p><p>Results</p><p>Among males, particularly those homozygous for the long alleles of <i>AVPR1A</i> RS3 were vulnerable to childhood adversity for their social attachment in adulthood. A similar vulnerability to childhood adversity among long allele carriers was found on adulthood social integration, but here both males and females were influenced.</p><p>Limitation</p><p>Data were self-reported and childhood adversity data were retrospective.</p><p>Conclusions</p><p>Early-life stress influenced the relationship between <i>AVPR1A</i> genetic variants and social interaction. For social attachment, <i>AVPR1A</i> was of importance in males only. The findings add to previous reports on higher acute vulnerability to stress in persons with long <i>AVPR1A</i> RS3 alleles and increased AVP levels.</p></div

ANCOVAs testing the effects of childhood adversity, <i>AVPR1A</i> RS3 genotypes (SS+SL <i>vs</i> LL) and their interaction on AVSI and AVAT.

<p><i>AVPR</i>: <i>AVPR1A</i> RS3.</p><p>AVSI: Availability of social integration.</p><p>AVAT: Availability of attachment.</p><p>CA: Childhood adversity.</p><p>ANCOVA adjusted for age, gender and education level.</p><p>^a Comparison between SS+SL and LL groups.</p><p>ANCOVAs testing the effects of childhood adversity, <i>AVPR1A</i> RS3 genotypes (SS+SL <i>vs</i> LL) and their interaction on AVSI and AVAT.</p

Path analysis of the chronicity of depression using the comprehensive developmental model framework

<p><b>Background</b> Depressive disorder is recognized as recurrent or chronic in the majority of affected individuals; but literature is not consistent about determinants of the disorder course. <b>Aims</b> To analyse the relationships between familial, personal and environmental characteristics in different life phases and their effects on the chronicity of depression in a population-based sample. <b>Methods</b> It was a longitudinal panel study with three waves (W1–W3) for 651 adult men and women with diagnosis of minor/major depression or dysthymia at W1 of the Swedish PART (mental health, work and relations) study. Risk factors and co-morbidities were assessed with questionnaires. The main outcome was an episode of minor/major depression or dysthymia at 10–12 years of follow-up (W3). Liability for depressive episodes was determined using exploratory structural equation modelling (SEM), following a path approach with step-wise specification searches. <b>Results</b> Most of the risk factors determined, directly or indirectly, depression severity at W3. Somatic trait anxiety, partner loss and other negative life events at W1, depressive symptoms at W2, and life difficulties and other dependent life events at W3 had direct effects on the outcome. <b>Conclusions</b> SEM model revealed complex and intertwined psychopathological pathways leading to chronicity of depression, given previous episodes, which could be assembled in two main mechanisms: a depressive-internalizing path and an adversity path comprised of life events. Pathways are simpler than those of depression occurrence, emphasizing the relevance of personality factors as depression determinants, and excluding disability levels, co-morbidities and social support. These novel findings need to be replicated in future studies.</p

The effect from <i>in utero</i> exposure to CBZ on hippocampus in 5 week-old mice.

<p>A) Down-regulation of hippocampal CA1 and CA3 pyramidal neurons after prenatal exposure of CBZ are still found in 5 week-old mice. Prenatal CBZ exposure does not affect neurons (granule cells) in the dentate gyrus (DG). B) A representative picture of hippocampus from one brain hemisphere in a five week-old mouse (scale bar 250 µm). High-magnification images illustrate cell morphology of granule cells in DG and pyramidal cells in CA1 and CA3, where the stereological cell-counting were performed. n = 8 controls, n = 7 CBZ treated animals, ** <i>P</i> = 0.0004</p

The effects of prenatal CBZ exposure on learning and memory investigated in the Morris water maze test.

<p>Figure panels 5 A–D describe the six training days and panels 5 E–H the retention test. <i>Training sessions</i>. 5A) There was no significant difference, but a trend, that CBZ-exposed mice were impaired in their ability to improve their escape latency to the hidden platform by training (<i>P</i> = 0.098). B) The CBZ-exposed mice had a significantly different swimming distance pattern over training compared to the control mice (<i>P</i> = 0.025). After training number 2, the CBZ-exposed mice reduced their swimming distance less by training than the control mice did.C) There was no significant difference in change of swimming speed over time between the CBZ-exposed mice and the controls during training (<i>P</i> = 0.39). D) Although there was no effect of training on the time the mice in both groups swam near the walls of the pool (thigmotaxic swimming) (<i>P</i> = 0.44), the CBZ-exposed mice tended to have higher thigmotaxic swimming all the days of training (<i>P</i> = 0.073). <i>Retention</i>. 5E) There was no significant difference in time for the CBZ-exposed and the control mice to find the former platform position, escape latency (<i>P</i> = 0.44). F) The two groups of mice spent the same proportion of total swim time in the target quadrant, where the former platform position was (<i>P</i> = 0.38). G) The number of times crossing the platform position did not differ between CBZ-exposed and control mice (<i>P</i> = 0.79). H) Thigmotaxic swimming; CBZ-exposed mice swam significantly longer time near the walls of the pool during retention (<i>P</i> = 0.0092) compared to controls, suggesting that they were more stressed. Bars indicate mean values and error bars indicate ±SEM. ** P<0.01, n = 10 CBZ-exposed mice, n = 11 control mice.</p

The effect from <i>in utero</i> exposure to CBZ on newborn mice.

<p>A) Prenatal exposure of CBZ reduces the number of mature pyramidal neurons in hippocampal CA1 and CA3 regions in the newborn mouse. A newborn control mouse hippocampus (B) and a CBZ treated mouse (C). The brown cells (NeuN-immunoreactive cells), which are indicative of mature neurons are more frequently occurring in the non-treated animals (B). There are few NeuN-immunoreactive cells in the newborn mouse dentate gyrus (DG), in agreement with that granule cells mature at later developmental stages compared to pyramidal cells in the CA1 and CA3 regions and in the hilus (H) region. The analysis is performed in the dorsal hippocampus. Values are mean ±SEM. n = 8 controls, n = 7 CBZ treated animals, ** <i>P</i> = 0.0013. Scale bar: B) 100 µm C) 25 µm.</p

Prenatal exposure to carbamazepine (CBZ) influences mouse body weight. Exposed mice had a lower body weight than non-exposed mice.

<p>The weight is presented in grams and as mean ±SEM (<i>n</i>).</p><p>***P<0.001 compared to non-exposed mice.</p