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Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting‐state functional connectivity (rs‐FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs‐FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co‐twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co‐twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment. [ABSTRACT FROM AUTHOR]

Background Several studies have shown that the in utero environment, which can be indexed by birth weight (BW), is associated with cortical morphology in adolescence and adulthood. Work in monozygotic (MZ) twins suggests that this association is driven by non-shared environmental factors. This correlation could be the result of in utero impacts on DNA methylation. The aim of the present study with MZ twins is to replicate the association between discordance in BW and brain morphology and test whether discordance in DNA methylation mediates this relationship. Methods One hundred and four adolescent MZ twins (52 pairs, of which 42% were male pairs) who have been followed regularly since birth underwent T1 weighted structural MRI, and epigenome-wide assessment of DNA methylation from saliva at age 15. Results Co-twins had very similar measures of DNA methylation and cortical morphology. Higher BW members of a twin pair had increased total cortical surface area, and decreased cortical thickness compared to their lower BW sibling. BW Discordance was positively associated with both cortical surface area and cortical volume discordance. Genes involved in neurodevelopment were tentatively identified as mediators of both the BW - cortical volume, and BW- cortical surface area relationships. Conclusions The association between BW and cortical morphology in adolescence appears to be attributable to in utero environmental effects, and DNA methylation may play a role in mediating this relationship. Hum Brain Mapp 38:2037-2050, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women. Method Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays. Results Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function. Discussion Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:874-882) [ABSTRACT FROM AUTHOR]

Background The neurobiology of risk for alcohol use disorders ( AUDs) remains poorly understood. Individual differences in vulnerability, though, have been indicated by subjective responses to alcohol ingestion and personality traits. Methods To investigate the relationship between these features and striatal dopamine (DA) responses to alcohol, we studied 26 healthy young social drinkers (21.3 ± 3.0 years old; 10.7 ± 8.8 drinks/wk) at varying risk for alcoholism. Each participant received 2 positron emission tomography [11C]raclopride scans after administration of either placebo or oral alcohol (1 ml/kg body weight of 94% alcohol, 0.75 g/kg) in a randomized and counterbalanced design. Results Subjects with high-risk subjective responses to alcohol had more family members with AUDs, greater alcohol use problems, and, in response to the alcohol challenge, significant decreases in [11C]raclopride binding indicative of increased extracellular DA. In contrast, low-risk subjects exhibited increases in [11C]raclopride binding in response to alcohol. The results were similar when risk groups were based on personality traits, although statistically less robust. Conclusions Changes in striatal DA in response to alcohol ingestion may be a neurobiological marker of vulnerability to AUDs. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: In laboratory animals, environmental stressors markedly activate the mesocortical dopamine system. The present study tested whether this occurs in humans. Methods: The effects of a laboratory psychological stressor (Montreal Imaging Stress Task, MIST) on mesocortical dopamine release in healthy young adults (11 males, mean age ± SD, 20.6 ± 2.4 years) was measured using positron emission tomography and [18F]fallypride. Each subject was scanned in two separate days in counterbalanced order: one with the MIST and one with the control task. Binding potential (BPND) maps of the whole brain were calculated for each scan, using a simplified reference tissue compartmental model. Then BPND was compared between subjects. Heart rate, galvanic skin response, and salivary cortisol level were measured during the scans. Results: The psychological stressor significantly decreased [18F]fallypride binding values in the dorsal part of the medial prefrontal cortex (dmPFC), corresponding to the rostal part of the cingulate motor zone. The greater the stress-induced decrease in [18F]fallypride binding in the dmPFC, the greater the stress-induced increases in heart rate. Conclusions: The present study provides evidence of stress-induced dopamine release in the mPFC in humans, in vivo. Synapse 67:821-830, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]