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Appropriate reactions toward emotional stimuli depend on the distribution of prefrontal attentional resources. In mid-adolescence, prefrontal top-down control systems are less engaged, while subcortical bottom-up emotional systems are more engaged. We used functional magnetic resonance imaging to follow the neural development of attentional distribution, i.e. attending versus ignoring emotional stimuli, in adolescence. 144 healthy adolescents were studied longitudinally at age 14 and 16 while performing a perceptual discrimination task. Participants viewed two pairs of stimuli – one emotional, one abstract – and reported on one pair whether the items were the same or different, while ignoring the other pair. Hence, two experimental conditions were created: “attending emotion/ignoring abstract” and “ignoring emotion/attending abstract”. Emotional valence varied between negative, positive, and neutral. Across conditions, reaction times and error rates decreased and activation in the anterior cingulate and inferior frontal gyrus increased from age 14 to 16. In contrast, subcortical regions showed no developmental effect. Activation of the anterior insula increased across ages for attending positive and ignoring negative emotions. Results suggest an ongoing development of prefrontal top-down resources elicited by emotional attention from age 14 to 16 while activity of subcortical regions representing bottom-up processing remains stable. [ABSTRACT FROM AUTHOR]

Background While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100–200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects. [ABSTRACT FROM AUTHOR]

Abstract: Several studies report differences between adults and adolescents in reward processing and impulsivity. Consistently, adolescents are more impulsive in their decision making, as measured by intertemporal choice tasks. Since impulsivity affects an individual’s perception and neural processing of rewards, it is unclear whether previously reported differences in brain activation between adults and adolescents are primarily due to maturation of the brain reward system or differences in impulsivity (i.e. discounting behaviour). To disentangle this, we analysed data from 235 adolescents and 29 adults who performed an intertemporal choice task in which monetary rewards were adapted to individual impulsivity. Using functional magnetic resonance imaging (fMRI), we measured brain activity and assessed impulsivity and consistency of choices at the behavioural level. Although adolescents discounted delayed rewards more steeply than adults, when controlling for impulsivity, neural processing of reward value did not differ between groups. However, more impulsive subjects showed a lower brain response to delayed rewards, independent of age. Concerning decision making, adolescents exhibited a lower consistency of choices and less brain activity in the parietal network than adults. We conclude that processing of the value of prospective delayed rewards is more sensitive to discounting behaviour than to chronological age. Lower consistency of intertemporal choices might indicate ongoing maturation of parietal brain areas in adolescents. [Copyright &y& Elsevier]

Purpose: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. Design: Sibling correlation study and genome-wide association study (GWAS). Participants: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. Methods: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. Main Outcome Measures: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. Results: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2×10–5), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3×10–9), which was confirmed in the replication samples (OR, 1.38; P = 7.4×10–14 for combined discovery and replication analysis). Conclusions: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Treatment options for social cognition and negative symptoms in schizophrenia spectrum disorders (SSD) remain limited. Oxytocin could be a promising augmentation approach, but the social context influences the effect in humans. This pilot study hypothesized that oxytocin in a positive social setting through mindfulness-based group therapy (MBGT) would positively affect empathy and negative symptoms as well as affect and stress in an exploratory approach in SSD. An experimental, randomized, double-blinded (participants, psychotherapists), placebo-controlled pilot study with 41 individuals with SSD was conducted at the Charité – Universitätsmedizin Berlin. Oxytocin or placebo (24 I.U.) was administered intranasally 45 min before two sessions of MBGT each. A 2 × 2 mixed model ANCOVA design was calculated to assess empathy by the Interpersonal Reactivity Index and the Multifaceted Empathy Test and negative symptoms by the Self-Evaluation of Negative Symptoms. No benefit of oxytocin compared to placebo on empathy was observed, but significant between-group differences favoring oxytocin were found regarding the negative symptoms Diminished emotional range and Avolition. Negative affect and stress were significantly reduced compared to baseline. Mindfulness increased in both groups. Results indicated protocol adherence and retention rate of 91.1%, a drop-out rate of 8.9 % and a completion of 96 % of all sessions by the participants. No severe adverse events or side effects were reported. Our findings indicate proof-of-concept and suggest a potential role of oxytocin on negative symptoms and related variables in SSD in combination with MBGT. Future research should examine the stability of these effects with larger sample sizes. • Mindfulness-based group therapy works as positive social context for oxytocin. • No additional effect of oxytocin and mindfulness on empathy in schizophrenia. • Positive effect of oxytocin and mindfulness on negative symptoms in schizophrenia. • Decreased negative affect by oxytocin plus mindfulness for schizophrenia. • Stress reduction by oxytocin in combination with mindfulness for schizophrenia. [ABSTRACT FROM AUTHOR]

While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (r g = 0.159; P = 5.05 × 10−10), cigarettes-smoked-per-day (r g = 0.094; P = 0.006), and age-of-onset of smoking (r g = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (r g = 0.624, P = 0.002) and cigarettes-smoked-per-day (r g = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10−5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10−8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts. [ABSTRACT FROM AUTHOR]