Prenatal Drug Exposure Affects Neonatal Brain Functional Connectivity

Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala–frontal, insula–frontal, and insula–sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala–frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention

Enhancing stress reactivity and wellbeing in early schizophrenia: A pilot study of individual coping awareness therapy (I-CAT)

Dear Editors: Positive psychology strategies and mindfulness are two non-traditional approaches to psychotherapy increasingly employed to aid recovery from psychosis (Shonin et al. 2014; Slade 2010). Positive psy-chology interventions focus on increasing experiences of positive emo-tions to improve wellbeing (Rashid 2015), while mindfulness interventions reduce stress reactivity, and facilitate experiences of pos-itive emotions (Geschwind et al. 2011; Gu et al., 2015)

A functional genomic perspective on human well-being

To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences

C-tactile afferent stimulating touch carries a positive affective value

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major—smile muscle, positive affect & corrugator supercilii—frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly

Emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release through mechanically-delivered massage in males

The neuropeptide oxytocin plays an important role in social behavior, parenting, and affectionate touch and there is some evidence that oxytocin release can be stimulated by massage or affectionate touch. We examined the effects of massage applied by a massage seat cover on salivary oxytocin levels in two exploratory studies using within-subject designs. In Study 1 massage effects on oxytocin levels were examined in a sample of N=20 healthy female participants. Effects of a 15-min massage session were compared to a control condition during which participants sat on a comfortable chair without a massage seat cover. Salivary oxytocin levels were measured at baseline and up to three hours after the session. We found that massage attenuated oxytocin decreases over time, indicating that massage stimulates oxytocin release. In Study 2, we examined whether effects of massage in N=46 healthy male participants depend on experiences of emotional maltreatment. In addition, we examined whether enhanced oxytocin levels after massage affect the use of excessive handgrip force in response to infant crying and laughter as measured with a handgrip dynamometer. Our findings show that massage results in elevated oxytocin levels compared to a control condition, but that the effects of massage are dependent on experiences of emotional maltreatment. Men with experiences of emotional maltreatment showed lower oxytocin levels, which did not increase after massage. Furthermore, we found that high oxytocin levels after massage were related to reduced handgrip force during exposure to infant crying and laughter, indicating that massage stimulates a sensitive response to infant signals by stimulating oxytocin release. Although massage did not affect oxytocin levels in individuals with experiences of maltreatment, it reduced the use of handgrip force in response to infant crying and laughter in these individuals. Our findings indicate that emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release

Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress

Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61-67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (P>0.001): methylation increased from pre- to post-stress (P=0.009) and decreased from post-stress to follow-up (P>0.001). This decrease was also found in a second target sequence of OXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR-which may in part reflect changes in blood cell composition-but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders