The domain-variant indirect association between electrophysiological response to reward and ADHD presentations is moderated by dopaminergic polymorphisms.

BACKGROUND: Understanding the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD) may necessitate decomposition of the heterogeneous clinical phenotype into more homogeneous intermediate phenotypes. Reinforcement sensitivity is a promising candidate, but the exact nature of the ADHD-reward relation - including how, for whom, and to which ADHD dimensions atypicalities in reward processing are relevant - is equivocal. METHODS: Aims were to examine, in a carefully phenotyped sample of adolescents (N = 305; Mage = 15.30 years, SD = 1.07; 39.7% girls), whether functional dopaminergic polymorphisms implicated in both reward processing and ADHD (1) are differentially associated with event-related potentials (ERPs) of reward anticipation at distinct levels of ADHD risk (nno risk = 174, nat-risk = 131, ndiagnosed = 83); and (2) moderate the indirect effect of dispositional affectivity on the association between ERPs and ADHD domains. RESULTS: In adolescents at-risk for or with ADHD, carrying a hypodopaminergic allele was associated with enhanced ERPs of attention allocation to cue and attenuated ERPs of anticipatory attention to feedback. No associations were observed in adolescents not at-risk for or without ADHD. Controlling for age and sex, both the negative indirect effect of positive affectivity (PA) on the association between ERPs and inattention and the positive indirect effect of PA on the association between ERPs and hyperactivity/impulsivity were supported only for those with high activity dopamine transporter (DAT) alleles. CONCLUSIONS: Reward and affective processing are promising intermediate phenotypes relevant to disentangling ADHD developmental pathways. Consistent with developmental multifinality, through the successive effects of reward anticipation and positive affectivity, functional dopaminergic variants may confer protection against inattention or risk for hyperactivity/impulsivity.

The Association Between Prenatal Maternal Stress and Adolescent Affective Outcomes is Mediated by Childhood Maltreatment and Adolescent Behavioral Inhibition System Sensitivity.

Prenatal maternal stress is linked to offspring outcomes; however, there is little research on adolescents, behavioral, transdiagnostic outcomes, or the mechanisms through which relations operate. We examined, in N = 268 adolescents (Mage = 15.31 years; SD = 1.063; 57.8% boys) whether prenatal maternal stress is associated with adolescent affective outcomes; whether this association is mediated, serially, by childhood home atmosphere and adolescent behavioral inhibition system (BIS) sensitivity; and whether mediational effects are moderated by adolescent attention-deficit/hyperactivity disorder or maternal internalizing symptomology. Prenatal maternal daily stress and major life events were associated with adolescent outcomes through childhood negative atmosphere/neglect and BIS sensitivity, with no evidence of moderation. Results have implications regarding the effect of prenatal maternal stress on offspring outcomes and regarding corresponding sensitive periods.

Do regulatory T cells contribute to Th1 skewness in obesity?

BACKGROUND: Recent data suggest that an increased prevalence of interferon-gamma (IFN-gamma) producing CD4 (+) cells is present in obesity. Regulatory T cells (Tregs) have a strong impact on activation and proliferation of CD4 (+) lymphocytes. Data are not available about Tregs and their possible contribution to chronic mild inflammation in obesity. DESIGN: We investigated the prevalence of Tregs in obese children. We also collected data about dendritic cells and monocytes (so-called antigen presenting cells, APCs), important modulators of Tregs and we determined the cytokine production of CD4 (+) lymphocytes, the main target cells of Tregs. METHODS: Twelve obese children and 10 healthy age-matched controls have been enrolled. For flow cytometric analyses, peripheral blood mononuclear cells were used. We determined the prevalence of Tregs by Foxp3 expression of CD4 (+) cells; prevalence of myeloid and plasmacytoid dendritic cells (DCs); prevalence of tumor necrosis factor (TNF)-alpha and interleukin(IL)-12 producing monocytes; and prevalence of IL-2, IL-4 and IFN-gamma producing CD4 (+) cells. RESULTS: The prevalence of Tregs, DCs, TNF-alpha and IL-12 producing macrophages, IL-2 and IFN-gamma producing CD4 (+) cells was similar in both groups. The prevalence of IL-4 producing CD4 (+) cells was lower in obese children than in healthy controls (p=0.028). The ratio of IFN-gamma (+)/ IL-4 (+) CD4 (+) cells was higher in obese children than in those with normal weight (p=0.046). CONCLUSIONS: CD4 (+) reactions are polarized toward Th1 direction in obesity. The unaltered number of Treg and APCs suggests that these immune regulator cells do not contribute to altered immune status in obese children.

Investigation of regulatory T cells in anorexia nervosa.

OBJECTIVE: The aim of our study was to determine, how severe calorie restriction in anorexia nervosa (AN) may influence regulatory T (Treg) cells and their cellular networks, that is, their main inducers (dendritic cells (DC) and monocytes) and their target cells, CD4+ lymphocytes. DESIGN: We measured the prevalence of Tregs, myeloid and plasmocytoid DC. The prevalence of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12-positive monocytes, IL-2, IL-4 and interferon (IFN)-gamma positive CD4+ cells was determined by intracellular staining after activation. SETTING AND SUBJECTS: In total, 21 AN patients and 19 healthy age-matched controls (body mass index values, median (range): 14.9 (11.1-17.4) vs 23.2 (19.5-27.4) kg/m(2)) have been recruited. RESULTS: Prevalence of Tregs, DCs, TNF-alpha and IL-12-positive monocytes, IL-4 and IFN-gamma-producing CD4+ cells were similar in AN and controls. The prevalence of IL-2-positive CD4+ cells was somewhat lower in AN (% value, median (range): 12.05 (7.50-16.70) vs 14.40 (12.00-22.00), P<0.05). None of these parameters correlated with the patients' clinical characteristics. CONCLUSIONS: Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis is not affected by calorie and nutritional deficiency.