Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. METHODS: The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. RESULTS: After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1ß were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939). CONCLUSIONS: Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT: The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

Negative Symptoms and Functioning in Youth at Risk of Psychosis: A Systematic Review and Meta-analysis.

LEARNING OBJECTIVE: After participating in this activity, learners should be better able to:• Evaluate the relationship between negative symptoms and functioning in youth at clinical high risk for psychosis. AIM: Youth at CHR for psychosis often demonstrate significant negative symptoms and poor functioning, though the magnitude and direction of the relationship between the two remains unknown. The objective of this systematic review is to summarize the relationship between negative symptoms and functioning in CHR samples. METHOD: Electronic databases CINAHL, EBM, Embase, MEDLINE, and PsycINFO were searched from inception. Studies were selected if they included any study that reported a relationship between negative symptoms and functioning in youth at clinical high risk (CHR). The correlation coefficient r was converted to Cohen's d, and all random-effects meta-analyses were performed using the transformed values. RESULTS: Forty-one studies met the inclusion criteria, including a total of 4574 individuals at CHR for psychosis. Negative symptom total scores were significantly associated with poorer global functioning (d, -1.40; 95% CI, -1.82 to -0.98; I = 79.4%; p < .001 [9 studies, n = 782]), social functioning (d, -1.10; 95% CI, -1.27 to -0.93; I = 10.40%; p < .001 [12 studies, n = 811]), and role functioning (d, -0.96; 95% CI, -1.17 to -0.76; I = 41.1%; p < .001 [9 studies, n = 881]). In addition, negative symptoms were consistently associated with poor premorbid functioning. When examining negative symptom domains, avolition, anhedonia, and blunted affect were each significantly and independently associated with poorer social functioning and role functioning. In terms of prediction models, negative symptoms contributed to the prediction of lower functioning across multiple studies. CONCLUSION: This meta-analysis demonstrates a strong relationship between negative symptoms and functioning in youth at clinical high risk for psychosis.

Premorbid social relationships and the course of schizophrenia in a 20-year follow-up study. / Relacje spoleczne przed wybuchem choroby a przebieg schizofrenii przez okres 20 lat.

OBJECTIVES: An important dimension indicating a growing risk of psychosis outbreak and its subsequent unfavorable course is deteriorating social functioning, especially the lack of sufficient social relationships. The aim of the study was to evaluate the association of the quality of social contacts and the scope of support system before the onset of the illness with treatment outcomes in clinical and social dimension in various time intervals of the 20-year illness course. METHODS: During the first hospitalization, an 80-person group living in Krakow and suffering from schizophrenia was selected, diagnosed according to DSM-IV-TR criteria and examined six times: at admission and discharge during first hospitalization, after 3, 7, 12 and 20 years. The analysis involved 55 persons (69% of the group included to the study) who went through all the examinations over a period of 20 years. Two-factor analysis of variance was used with one grouping factor (social contacts) and one repeated measures factor (follow-ups) for the results of GAF, BPRS, DSM-III Axis V and a series of simple linear regressions for the associations between these outcome indicators and the Surtees' Index of Social Support. RESULTS: Satisfactory, positive contacts before the outbreak of the illness translated, especially after 20 years, into better general and social functioning and fewer symptoms, especially negative ones. Awider social support before the outbreak was associated with better general and social functioning of patients and lesser severity of general, positiveand negative symptoms; however, in this last case the effect disappeared after 20 years. CONCLUSIONS: The quality and scope of social contacts before the outbreak of the illness, especially satisfactory relationship in non-familial milieu, are an important prognostic factor of amany-year beneficial clinical and social course of psychoses from the schizophrenia group.

Trajectories of internalising and externalising symptoms and inflammation in the general child population.

BACKGROUND: Elevations in inflammatory marker levels have been shown to precede internalising and externalising problems in the general child population. One study has found the reverse, that elevations in inflammatory marker levels in childhood follow internalising and externalising problems. However, the authors did not explore the role of the course of these problems in childhood or adjust for a number of potential confounders including psychosocial stressors and prenatal and perinatal exposures. AIMS: To investigate the association in childhood between the growth of internalising and externalising symptoms and levels of inflammatory markers, while accounting for potential confounders. METHODS: Using data from the Avon Longitudinal Study of Parents and Children, we tested the association between the trajectories of internalising (emotional and social) and externalising (hyperactivity and conduct) problems, at ages 4, 6, 8 and 9 years, and levels of C-reactive protein (CRP) and interleukin 6 (IL-6) at age 9 years. We analysed data (n = 4525) using latent growth curve modelling and linear regression. RESULTS: Children who had increasing levels of internalising symptoms over childhood were more likely to have higher levels of CRP and IL-6 at 9 years of age, even after adjustment for confounders. A one-unit increase in the rate of annual change of internalising symptoms was related to an increase of 12% and 8% in the level of CRP and IL-6, respectively. However, there was no evidence for an association between externalising symptoms and either inflammatory marker. CONCLUSIONS: This study is the first step towards identifying a robust pathway, via increases in emotional and social difficulties, to elevated inflammation in healthy children. This association, if causal, suggests that effective interventions for children experiencing chronic emotional and social difficulties could also have physical health benefits.

Development and Calibration of the TBI-QOL Ability to Participate in Social Roles and Activities and TBI-QOL Satisfaction With Social Roles and Activities Item Banks and Short Forms.

OBJECTIVE: To develop traumatic brain injury (TBI)-optimized versions of the Quality of Life in Neurological Disorders (Neuro-QoL) Ability to Participate in Social Roles and Activities and Satisfaction with Social Roles and Activities item banks, evaluate the psychometric properties of the item banks developed for adults with TBI, develop short form and computer adaptive test (CAT) versions, and report information to facilitate research and clinical applications. DESIGN: We used a mixed methods design to develop and evaluate Ability to Participate in Social Roles and Activities and Satisfaction with Social Roles and Activities items. Focus groups defined the constructs, cognitive interviews guided item revisions, and confirmatory factor analysis and item response theory methods helped calibrate item banks and evaluate differential item functioning related to demographic and injury characteristics. SETTING: Five TBI Model Systems centers in the United States. PARTICIPANTS: Community-dwelling adults with TBI (N=556). INTERVENTIONS: None. OUTCOME MEASURES: Traumatic Brain Injury-Quality of Life (TBI-QOL) Ability to Participate in Social Roles and Activities and TBI-QOL Satisfaction with Social Roles and Activities item banks. RESULTS: Forty-five Ability to Participate in Social Roles and Activities and 41 Satisfaction with Social Roles and Activities items demonstrated good psychometric properties. Although some of the items are new, most were drawn from analogous banks in the Neuro-QoL measurement system. Consequently, the 2 TBI-QOL item banks were linked to the Neuro-QoL metric, and scores are comparable with the general population. All CAT and short forms correlated highly (>0.90) with the full item banks and demonstrate comparable construct coverage and measurement error. CONCLUSION: The TBI-QOL Ability to Participate in Social Roles and Activities and TBI-QOL Satisfaction with Social Roles and Activities item banks are TBI-optimized versions of the Neuro-QoL Ability to Participate in Social Roles and Activities and Satisfaction with Social Roles and Activities item banks and demonstrate excellent measurement properties in individuals with TBI. These measures, particularly in CAT or short form format, are suitable for efficient and precise measurement of social outcomes in clinical and research applications.

Developing and testing the F-SIM, a measure of social inclusion for people with mental illness.

Social inclusion is an important contributor to good mental health and greater mental health outcomes for people with psychiatric disorders. A psychometrically-sound measure of social inclusion is required to facilitate progress in this area. The aim here was to report on preliminary findings from a novel, user-friendly measure of social inclusion that comprehensively assesses the construct. Preliminary testing of the Filia Social Inclusion Measure (F-SIM) was conducted with ninety participants (30 consumers; 30 family members/carers; 30 community members). Participants completed the self-report measure and a usability questionnaire. Preliminary findings demonstrated poorer social inclusion for people with mental illness compared to those without, with differences seen in each of five domains (housing and services, social functioning, occupational functioning, finances and health). Differences were also seen regarding family members or carers, with consistently poorer social inclusion than general community members observed. Participants reported the F-SIM as easy to use, and considered it to measure social inclusion well, indicating good face validity. The F-SIM demonstrates an ability to differentiate between groups. Implications for use and suggestions for future research are detailed. Following further psychometric assessment, the F-SIM will have wide applicability in clinical and research settings.

Strengthening the Voice of Those with Mental Health Issues: A Community Approach to Developing a Mental Health Identification System.

This article describes how an action research approach was used to involve a community of individuals with mental health issues and their support systems in the development and adoption of a mental health identification (ID) card. The intent of the card was to provide individuals with mental health issues a way to communicate and manage the idiosyncratic nature of their behaviors. A credit card-size ID card was developed that has the individual's picture, address, diagnosis, idiosyncratic behaviors, best approach with the individual when those behaviors are present, medications, allergies, and emergency contact information. Benefits and concerns about the ID system in regard to the cardholder, card recipients, the provision of consent, Health Insurance Portability and Accountability Act compliance, and the balancing of reducing and increasing stigmas and stereotypes emerged throughout the process. In the end, the ID card has come to be seen as a social justice mechanism that allows for communication and awareness for those with mental health issues.

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy.

OBJECTIVE: To examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy. METHODS: In collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA-exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first-choice treatments for many women with epilepsy of childbearing potential. RESULTS: Of the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA-exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA-exposed children had significantly more social problems than those exposed to LTG (-2.8, 95% confidence interval [CI] = -5.2 to -0.4; P = 0.022) or LEV (-3.2, CI: -6.1 to -0.3; P = 0.028), and significantly more attention problems than LEV-exposed children (-3.7, CI: -6.7 to -0.8; P = 0.013). LTG-exposed children had significantly more attention deficit (-9.2, CI: -17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV-exposed children (9.0, CI: 0.3-17.6; P = 0.042). SIGNIFICANCE: Compared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED-exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

The Psychology of Shoplifting: Development of a New Typology for Repeated Shoplifting.

Despite the damaging effects of shoplifting on individuals, the current literature offers little guidance for changing shoplifting behavior. One limitation in this area of research has been the failure to use empirically and theoretically sound methodologies to identify individuals' diverse characteristics and motivations. The present study addressed these limitations by developing an empirically and theoretically supported typology of the varied individuals who shoplift. Participants included 202 community individuals who reported repeated shoplifting and provided information about their shoplifting behavior, motivations, mental health, ethical attitudes, personal histories, and life circumstances. Cluster analyses revealed that the sample could be divided into six discrete groups. These clusters comprise a typology of shoplifting, including Loss-Reactive (28% of the sample), Impulsive (20%), Depressed (18%), Hobbyist (18%), Addictive-Compulsive (9%), and Economically Disadvantaged (7%) types. Each type comprises a unique pattern of shoplifting with unique needs. This research establishes a promising foundation for treating the diverse individuals who shoplift.

A systematic review of the impact of social cognitive deficits on psychosocial functioning in major depressive disorder and opportunities for therapeutic intervention.

Social cognition is the ability to identify, perceive and interpret socially relevant information from the external world. It is an important adaptive trait, but is frequently affected in major depressive disorder by a mood-congruent interpretive bias. The present review examined the existing body of literature to determine (i) the impact social cognitive deficits in depression have on psychosocial functioning; and (ii) the utility of psychotropic, psychological and procedural interventions employed to target these deficits. A total of 107 studies met inclusion criteria for review. Social cognitive performance was found to adversely impact depressed patients' psychosocial functioning across the key domains of general cognitive functioning and quality of life. Secondly, many current therapies were found to have a normalising effect on the social cognitive abilities of subjects with major depressive disorder, both at a neural and functional level. In particular, certain anti-depressant medications corrected facial affect recognition deficits, while several psychotherapeutic approaches improved impairments in theory of mind and negative interpretive bias.

Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder.

Impairments in social interaction and verbal and non verbal communication are among the main features of Autism Spectrum Disorder (ASD). The causes of ASD are still unknown but the research efforts of the last decade have identified a number of factors (rare gene mutations, gene variations and adverse environmental events) that, interacting in complex ways, affect early brain development. The clinical evidence that prenatal exposure to the antiepileptic drug valproate (VPA) is associated with increased risk of neurodevelopmental delay, cognitive deficits and autism in children, has drawn the attention of scientists on VPA as a tool to unravel the environment contribution to ASD risk in children. In agreement with the clinical evidence, rodents prenatally exposed to VPA display behavioral anomalies resembling ASD symptoms. The mechanisms by which administration of VPA in pregnancy increases the risk of autism are still far to be clear as are still undetermined the specific targets of VPA in the developing brain both in humans and rodents. However, the robustness of the behavioral alterations, mainly in the social domain, and the neural/molecular changes revealed so far support the VPA model as a reliable instrument to investigate the neural underpinnings of social impairment. Here we provide an update of preclinical studies on prenatal exposure to VPA in rodents with a focus on the social and communication deficits induced by VPA, discussing potential pitfalls and future directions in this research field and corroborating the potential of the VPA model to identify new pharmacological targets for ASD. This article is part of the Special Issue entitled 'The neuropharmacology of social behavior: from bench to bedside'.

Factors influencing hospital admission among patients with autopsy-confirmed dementia.

BACKGROUND: The symptoms of geriatric syndromes and the behavioural and psychological symptoms of dementia (BPSD), in addition to clinical conditions, are associated with hospital admission among dementia patients. However, the principal factors that necessitate hospital admission among dementia patients have not been fully elucidated. METHODS: We retrospectively reviewed the data in the medical and autopsy reports of patients who had been treated at a hospital in Toyohashi, Japan. Each patient had been hospitalized sometime between 2012 and 2016 and underwent a brain autopsy. Dementia and the subtypes of dementia were diagnosed neuropathologically. Information about patients' general backgrounds, clinical conditions at the time of admission, and the geriatric syndrome symptoms and BPSD before admission was collected; comparisons were then made between patients with and without dementia and among those with the different major subtypes of dementia. Then, the factors relating to hospital admission of dementia patients were comprehensively evaluated by using principle component analysis. RESULTS: Of the 128 eligible patients, 100 (78.1%) had dementia. In the comparison of patients with and without dementia, patients without dementia were younger at both admission (P = 0.034) and death (P = 0.003). Among the patients with dementia with Lewy bodies, delusions had a significantly high prevalence (P = 0.014). Principal component analysis identified nine components (disinhibition, irritability/lability, agitation/aggression, anxiety, delusions, sleep/night-time behaviour disorders, hallucinations, aberrant motor behaviour, and speech impairment) as the principal factors related to hospital admission among dementia patients. Thus, BPSD were identified as principal factors. CONCLUSIONS: Compared to other factors, BPSD are more likely to cause dementia patients to be admitted to hospital. The present results indicate that measures should be taken to ameliorate the difficulties associated with caring for patients with BPSD at home.

Determinants of social behavior deficits and recovery after pediatric traumatic brain injury.

Traumatic brain injury (TBI) during early childhood is associated with a particularly high risk of developing social behavior impairments, including deficits in social cognition that manifest as reduced social interactions, with profound consequences for the individuals' quality of life. A number of pre-injury, post-injury, and injury-related factors have been identified or hypothesized to determine the extent of social behavior problems after childhood TBI. These include variables associated with the individual themselves (e.g. age, genetics, the injury severity, and extent of white matter damage), proximal environmental factors (e.g. family functioning, parental mental health), and more distal environmental factors (e.g. socioeconomic status, access to resources). In this review, we synthesize the available evidence demonstrating which of these determinants influence risk versus resilience to social behavior deficits after pediatric TBI, drawing upon the available clinical and preclinical literature. Injury-related pathology in neuroanatomical regions associated with social cognition and behaviors will also be described, with a focus on findings from magnetic resonance imaging and diffusion tensor imaging. Finally, study limitations and suggested future directions are highlighted. In summary, while no single variable can alone accurately predict the manifestation of social behavior problems after TBI during early childhood, an increased understanding of how both injury and environmental factors can influence social outcomes provides a useful framework for the development of more effective rehabilitation strategies aiming to optimize recovery for young brain-injured patients.

Deviant Peers and Adolescent Risky Behaviors: The Protective Effect of Nonverbal Display of Parental Warmth.

This study examines whether nonverbal displays of parents' warmth during an in-lab conflict discussion mitigate the links between affiliation with deviant peers and risky behaviors. A sample of 107 youth and their parents participated in a study spanning from mid-adolescence (T1) to late adolescence (T2). At T1, family members discussed a contentious issue, which was coded for parents' nonverbal warmth. At T1 and T2, youth reported on their friends' and their own risky behaviors. Fathers' warmth moderated each prospective association between deviant peers and risky behaviors. Mothers' warmth did not emerge as a significant moderator. Girls, in particular, benefitted from fathers' warmth as a buffer in the trajectory from T1 risky behaviors to T2 risky behaviors and deviant peers.

Interventions and social functioning in youth at risk of psychosis: A systematic review and meta-analysis.

AIM: Youth at clinical high risk (CHR) for psychosis often exhibit difficulties in social functioning and poorer social functioning may be predictive of transition to a psychotic disorder. Therefore, the primary objective of this systematic review was to summarize the impact of all interventions on social functioning in CHR samples. METHOD: Electronic databases PsycINFO, CINAHL, Embase, EBM, and MEDLINE were searched from 1951 to June 2017. Studies were selected if they included any intervention that reported changes in social functioning in youth at CHR. Data were evaluated using random effects pairwise meta-analyses, stratified by time, and reported as the standardized mean difference (SMD). RESULTS: Nineteen studies met our inclusion criteria, including a total of 1513 CHR participants. The mean age was 20.5 years and 47% were male. Cognitive behavioural therapy (4 studies) did not significantly improve social functioning at 6 months (SMD = 0.06; 95% confidence interval [CI] = -0.35, 0.46), 12 months (SMD = -0.15; 95% CI = -0.38, 0.08) and 18 months (SMD = 0.20; 95% CI = -0.10, 0.50). Omega-3 (2 studies) did not significantly improve social functioning at 6 months (SMD = 0.01; 95% CI = -0.21, 0.24) and 12 months (SMD = -0.08; 95% CI = -0.33, 0.17). Lastly, cognitive remediation (3 studies) did not significantly improve social functioning at 2- to 3-month follow-up (SMD = 0.13, 95% CI = -0.18, 0.43). CONCLUSIONS: This systematic review and meta-analysis demonstrated that no treatment significantly improved social functioning in youth at CHR. Future randomized control trials are required that are designed to target and improve social functioning in youth at CHR for psychosis.

Autism-Related Variation in Reciprocal Social Behavior: A Longitudinal Study.

Deficits in reciprocal social behavior are a characterizing feature of autism spectrum disorder (ASD). Autism-related variation in reciprocal social behavior (AVR) in the general population is continuously distributed and highly heritable-a function of additive genetic influences that overlap substantially with those which engender clinical autistic syndromes. This is the first long-term prospective study of the stability of AVR from childhood through early adulthood, conducted via serial ratings using the Social Responsiveness Scale, in a cohort-sequential study involving children with ASD, other psychiatric conditions, and their siblings (N = 602, ages = 2.5-29). AVR exhibits marked stability throughout childhood in individuals with and without ASD.

Trajectories of behavior, attention, social and emotional problems from childhood to early adulthood following extremely preterm birth: a prospective cohort study.

To investigate trajectories of behavior, attention, social and emotional problems to early adulthood in extremely preterm survivors compared to a term-born comparison group. Longitudinal analysis of a prospective, population-based cohort of 315 surviving infants born < 26 completed weeks of gestation recruited at birth in 1995, from the UK/Republic of Ireland, and a term-born comparison group recruited at age 6. The parent-report Strengths and Difficulties Questionnaire was completed at age 6, 11, 16 and 19 years. The Total Behavioral Difficulties Score was 4.81 points higher in extremely preterm individuals compared to their term-born peers over the period (95% CI 3.76-5.87, p < 0.001) and trajectories were stable in both groups. The impact of difficulties on home life, friendships, school or work and/or leisure activities was greater in the EPT group (RR 4.28, 95% CI 2.89-6.35, p < 0.001), and hyperactivity/inattention and peer problems accounted for the largest differences. A clinically significant behavioral screen at age 2.5 was associated with a higher Total Behavioral Difficulties Score from 6 years onwards in extremely preterm participants (Mean difference 6.90, 95% CI 5.01-8.70, p < 0.0.01), as was moderate/severe cognitive impairment at last assessment (Mean difference: 4.27, 95% CI 2.76-5.77, p < 0.001). Attention, social and emotional problems in extremely preterm individuals persist into early adulthood with significant impact on daily life. A positive behavioral screen in infancy and moderate/severe cognitive impairment are associated with early adult outcomes.