Boys' serotonin transporter genotype affects maternal behavior through self-control: a case of evocative gene-environment correlation.

Self-control, involving processes such as delaying gratification, concentrating, planning, following instructions, and adapting emotions and behavior to situational requirements and social norms, may have a profound impact on children's adjustment. The importance of self-control suggests that parents are likely to modify their parenting based on children's ability for self-control. We study the effect of children's self-control, a trait partially molded by genetics, on their mothers' parenting, a process of evocative gene-environment correlation. Israeli 3.5-year-old twins (N = 320) participated in a lab session in which their mothers' parenting was observed. DNA was available from most children (N = 228). Mothers described children's self-control in a questionnaire. Boys were lower in self-control and received less positive parenting from their mothers, in comparison with girls. For boys, and not for girls, the serotonin transporter linked polymorphic region gene predicted mothers' levels of positive parenting, an effect mediated by boys' self-control. The implications of this evocative gene-environment correlation and the observed sex differences are discussed.

Shiatsu as an adjuvant therapy for schizophrenia: an open-label pilot study.

CONTEXT: Studies have suggested a possible role for shiatsu in treating a variety of mental and physical ailments. OBJECTIVE: To determine if shiatsu can provide clinical benefit to individuals diagnosed with schizophrenia. DESIGN: An open-label pilot study. SETTING: An inpatient psychiatric ward at Herzog Memorial Hospital, Jerusalem, Israel. PATIENTS: Twelve hospitalized patients with chronic schizophrenia. INTERVENTION: Shiatsu treatment provided in a course of eight 40-minute biweekly sessions over 4 weeks. MAIN OUTCOME MEASURES: All subjects were evaluated at baseline, 2 weeks, 4 weeks (end of treatment), and 12 weeks (followup). The tools used for assessment included the Clinical Global Impression (CGI), the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). Side effects were measured using the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: On all scales of psychopathology and side effects, the subjects showed a statistically and clinically significant improvement by the end of treatment. This improvement was maintained at the 12-week follow-up. These findings, while encouraging, must be considered preliminary and require confirmation and cross-validation in larger-scale controlled studies.

Hemisphere asymmetry in schizophrenia as revealed through line bisection, line trisection, and letter cancellation.

Individuals with schizophrenia are known to demonstrate reduced or reversed brain asymmetry. While much is known regarding anatomical brain asymmetry, little is known about how this affects the individual at the functional level. Based on the known leftward bias in normal individuals, the aim of this study was to explore whether any difference in this function would be noted in schizophrenia. This study therefore investigated the phenomenon of functional asymmetry in schizophrenia patients by means of the following tasks: line bisection, line trisection (assessing hemifield spatial neglect) and letter cancellation (assessing contralateral visuospatial exploration). Forty-five schizophrenia inpatients maintained on antipsychotic medication were evaluated. Transections were measured for accuracy, lateralization, and directional bias. In the line bisection task subjects indicated no pseudo-neglect, thus differing from a normal, leftward bias. In the line trisection there was a significant preference to perform the ambiguous instruction on the right side, with no consistent bias in accuracy. Irrespective of conditions, in the letter cancellation task there was always a significant tendency to succeed on the left third compared to the right third. Results may support findings in schizophrenia indicating decreased or altered function of the left hemisphere.

Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings.

The efficacy of compounds having agonistic activity at the glycine site associated with the N-methyl-D-aspartate receptor (NMDAR) is presently assessed in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric effects of NMDAR agonists in the healthy human organism are not known. We studied neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory co-agonist d-serine (DSR) in healthy subjects using a randomized, controlled crossover challenge design including a baseline assessment day and two DSR/placebo administration days. Thirty-five subjects aged 23-29 years participated in the study and received a 2.1 g orally administered DSR dose. The main outcome measures were the changes in scores of mood-related Visual Analogue Scale (VAS), Continuous Performance Test-Identical Pairs (CPT-IP), and Rey Auditory Verbal Learning Test (RAVLT). DSR acute administration: (1) was well tolerated and resulted at 2 h in ≥ 200 times increase in DSR serum levels; (2) elicited reduced VAS-measured depression and anxiety feelings; (3) improved attention and vigilance as measured by CPT-IP D-prime score; (4) preferentially improved performance in RAVLT list 7 reflecting ability to retain information over interference; (5) had significant but nonspecific effects on Category Fluency and Benton Visual Retention tests; and (6) did not affect glycine and glutamate serum levels. These data indicate that in healthy subjects, DSR reduces subjective feelings of sadness and anxiety and has procognitive effects that are overall opposed to the known effects of NMDAR antagonists. The findings are relevant to translational research of NMDAR function and the development of NMDAR-glycine site treatments for specific psychiatric entities. ClinicalTrials.gov: Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans; http://www.clinicaltrials.gov/ct2/show/NCT02051426?term=NCT02051426&rank=1; NCT02051426.

The dopamine D4 receptor gene shows a gender-sensitive association with cognitive empathy: evidence from two independent samples.

Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Specifically, a polymorphic region in the third exon of the Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors, often in an environment-sensitive manner. Empathy is thought to be an important motivator of prosocial behaviors and can be seen as multifaceted, combining cognitive empathy (CE) and emotional empathy (EE). In the current study, we analyzed the association between DRD4 and the 2 aspects of empathy, as well as the effect of gender on this association. In Study 1, a large sample of adult participants (N = 477) was inventoried for general empathy, CE, and EE and genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all empathy measures and no main effect of genotype was observed. It is important that a significant interaction between genotype and gender emerged specifically for CE, with women carriers of the 7R-allele scoring higher than noncarriers, whereas in men 7R-carriers scored lower than -7R. Notably, these findings were replicated in an independently recruited sample (N = 121) in Study 2. The current report shows that the DRD4 exon3 polymorphism is associated with CE and the direction of the association is gender-sensitive.

Hypnotizability is associated with a protective but not acquisitive self-presentation style.

Self-presentation refers to the behavioral strategies a person adopts to convey desired social images of oneself to other people. The Concern for Appropriateness Scale (CAS) measures a defensive and fearful social approach aimed at avoiding social threats whereas the Revised Self-Monitoring Scale (RSMS) measures an active and flexible social approach aimed at gaining power and status. In this study, a significant correlation was found between hypnotizability, as measured by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) scores and CAS (r = .43, p = .002) but not between hypnotizability and RSMS (r = .070, p = .631). These results suggest that a protective self-presentation style may incline certain individuals to cooperate with hypnotic suggestions.

Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self.

Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.

Preventive pharmacological treatment --an evolving new concept in schizophrenia.

Treatment for schizophrenia remains one of the major challenges of modern medicine. The development of innovative pharmacological approaches for this disorder can potentially alleviate tremendous human suffering and revolutionize mental health delivery systems. While current treatment guidelines for schizophrenia refer to the post-psychosis onset phase of illness, presently there is a strong resurgent interest in secondary prevention intervention applied during schizophrenia prodrome. This development stems largely from the recognition that neurobiological deficit processes associated with schizophrenia severity and chronicity are already active by the time clinical onset is recognized. Proposed preventive treatments include presently used medications and experimental compounds that hypothetically may influence ongoing pathophysiological processes earlier in their development. The future establishment of the early recognition and intervention concept in schizophrenia is critically dependent on the outcome of ongoing research assessing the feasibility of prodrome diagnosis, the efficacy of specific medications and the alleviation of the risks associated with early pharmacological treatment.

Defensive self-presentation style is associated with reduced prepulse inhibition.

Prepulse inhibition (PPI) of the startle response is a cross-species measure of sensorimotor gating that provides a valuable tool for assessing the capacity to effectively screen out irrelevant sensory input. Accumulating evidence suggests that PPI deficits may correlate with impairments in social cognition, i.e. the ability to construct representation about others, oneself and the relations between others and oneself. Social cognition deficits are commonly encountered within the framework of psychiatric disorders. In this study 113 healthy volunteers completed psychopyhsiological measures of sensorimotor gating (PPI) and social self-presentation style (the Concern for Appropriate (CAS) and the Revised Self-Monitoring (RSMS) scales). CAS measures a defensive and fearful social approach aiming at avoiding social threats; RSMS measures an active and flexible social approach aiming at gaining power and status. Analyses revealed an inverse correlation between PPI at the 120 ms prepulse-to-pulse interval and total CAS scores (r=-0.19, p=0.04), as well as with the Attention to Social Comparison Information (ASCI) subscale of the CAS (r=-0.23, p=0.01). These findings suggest that reduced PPI may contribute to the tendency to adopt a defensive and fearful "getting along" social approach. This study is, to our knowledge, the first to assess the relationship between sensorimotor gating and self-presentational style in humans. Its findings suggest that very basic perceptual deficits that can be assessed using the PPI paradigm, may reflect information processing abnormalities that impact negatively upon the perception of complex social interactions.

Hypnotizability and sensorimotor gating: a dopaminergic mechanism of hypnosis.

Dopaminergic mechanisms have been theorized to influence hypnotizability and sensorimotor gating. In this study, the authors investigated an association between sensorimotor gating, as measured by prepulse inhibition (PPI), and hypnotizability, as assessed by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). They found an inverse correlation between the SSHS:C and PPI. This finding, which replicates an earlier study, provides further evidence for a dopaminergic basis for hypnotizability and suggests additional avenues for research, including a method for possibly enhancing hypnotizability through pharmacological interventions.