Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Autistic traits in psychotic disorders: prevalence, familial risk, and impact on social functioning.

BACKGROUND: Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD. METHODS: In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16-50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS). RESULTS: For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms. CONCLUSIONS: Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

Attentional control and executive functioning in school-aged children: Linking self-regulation and parenting strategies.

Good parenting strategies can shape children's neurocognitive development, yet little is known about the nature of this relation in school-aged children and whether this association shifts with age. We aimed to investigate the relation between parenting strategies observed during a home visit and children's performance-based attentional control and executive functioning (N=98, aged 4-8years). Linear and curvilinear regression analyses showed that children of parents who were more supportive, were less intrusive, and asked more open-ended questions displayed better inhibitory control. In addition, children of parents who asked relatively more open-ended than closed-ended questions showed better performance on inhibition, working memory, and cognitive flexibility tasks. Curvilinear relations indicated the presence of an optimal amount of closed-ended and elaborative questions by parents-that is, not too few and not too many-which is linked to increased performance on attentional and inhibitory control in children. Higher parental intrusiveness and more frequent elaborative questioning were associated with decreased inhibitory control in younger children, whereas no such negative associations were present in older children. These results suggest that susceptibility to certain parenting strategies may shift with age. Our findings underscore the importance of adaptive parenting strategies to both the age and needs of school-aged children, which may positively affect their self-regulation skills.

Individual prediction of long-term outcome in adolescents at ultra-high risk for psychosis: Applying machine learning techniques to brain imaging data.

An important focus of studies of individuals at ultra-high risk (UHR) for psychosis has been to identify biomarkers to predict which individuals will transition to psychosis. However, the majority of individuals will prove to be resilient and go on to experience remission of their symptoms and function well. The aim of this study was to investigate the possibility of using structural MRI measures collected in UHR adolescents at baseline to quantitatively predict their long-term clinical outcome and level of functioning. We included 64 UHR individuals and 62 typically developing adolescents (12-18 years old at recruitment). At six-year follow-up, we determined resilience for 43 UHR individuals. Support Vector Regression analyses were performed to predict long-term functional and clinical outcome from baseline MRI measures on a continuous scale, instead of the more typical binary classification. This led to predictive correlations of baseline MR measures with level of functioning, and negative and disorganization symptoms. The highest correlation (r = 0.42) was found between baseline subcortical volumes and long-term level of functioning. In conclusion, our results show that structural MRI data can be used to quantitatively predict long-term functional and clinical outcome in UHR individuals with medium effect size, suggesting that there may be scope for predicting outcome at the individual level. Moreover, we recommend classifying individual outcome on a continuous scale, enabling the assessment of different functional and clinical scales separately without the need to set a threshold. Hum Brain Mapp 38:704-714, 2017. © 2016 Wiley Periodicals, Inc.

Neuropsychological assessment of aggressive offenders: a Delphi consensus study.

Objective: This study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression. Methods: An international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability. Results: The panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed. Conclusions: This research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.

The Association Between Chronic Tobacco Smoking and Brain Alterations in Schizophrenia: A Systematic Review of Magnetic Resonance Imaging Studies.

BACKGROUND AND HYPOTHESIS: The high co-occurrence of tobacco smoking in patients with schizophrenia spectrum disorders (SSD) poses a serious health concern, linked to increased mortality and worse clinical outcomes. The mechanisms underlying this co-occurrence are not fully understood. STUDY DESIGN: Addressing the need for a comprehensive overview of the impact of tobacco use on SSD neurobiology, we conducted a systematic review of neuroimaging studies (including structural, functional, and neurochemical magnetic resonance imaging studies) that investigate the association between chronic tobacco smoking and brain alterations in patients with SSD. STUDY RESULTS: Eight structural and fourteen functional studies were included. Structural studies show widespread independent and additive reductions in gray matter in relation to smoking and SSD. The majority of functional studies suggest that smoking might be associated with improvements in connectivity deficits linked to SSD. However, the limited number of and high amount of cross-sectional studies, and high between-studies sample overlap prevent a conclusive determination of the nature and extent of the impact of smoking on brain functioning in patients with SSD. Overall, functional results imply a distinct neurobiological mechanism for tobacco addiction in patients with SSD, possibly attributed to differences at the nicotinic acetylcholine receptor level. CONCLUSIONS: Our findings highlight the need for more longitudinal and exposure-dependent studies to differentiate between inherent neurobiological differences and the (long-term) effects of smoking in SSD, and to unravel the complex interaction between smoking and schizophrenia at various disease stages. This could inform more effective strategies addressing smoking susceptibility in SSD, potentially improving clinical outcomes.

A Cross-sectional Conceptual Replication and Longitudinal Evaluation of the PANSS-Autism-Severity-Score Measure Suggests it Does Not Capture Autistic Traits in Individuals With Psychosis.

BACKGROUND: Autism and psychosis co-occur at elevated rates, with implications for clinical outcomes, functioning, and suicidality. The PANSS-Autism-Severity-Score (PAUSS) is a measure of autism trait severity which has not yet been validated externally or longitudinally. STUDY DESIGN: Participants were derived from the GROUP and SCOPE datasets. Participants included 1448 adults with schizophrenia spectrum disorder (SSD), 800 SSD-siblings, 103 adults diagnosed with an autistic spectrum condition (ASC), and 409 typically-developing controls (TC). Analyses from the original validation study were conducted with SSD participants, and extended into ASC, SSD-sibling, and TC participants. Test-retest reliability of the PAUSS at 2-weeks and long-term stability 3 and 6-years was also examined. STUDY RESULTS: Results differed in important ways from the original validation. SSD participants reported higher PAUSS scores than other groups, with only a fraction of ASC participants scoring as "PAUSS-Autistic." Cronbach's alpha was acceptable for the SSD cohort only. Two-week stability of the PAUSS was fair to good for all PAUSS scores. Long-term stability was poor for most PAUSS items but fair for total PAUSS score. CONCLUSIONS: Results suggest that the PAUSS does not appear appropriate for assessing autism, with the low rate of PAUSS-Autistic in the ASC population suggesting the PAUSS may not accurately reflect characteristics of autism. The relative lack of long-term stability is cause for concern and suggestive that the PAUSS is capturing features of psychosis rather than autism traits.

Autistic Symptoms and Social Functioning in Psychosis: A Network Approach.

Psychotic and autistic symptoms are related to social functioning in individuals with psychotic disorders (PD). The present study used a network approach to (1) evaluate the interactions between autistic symptoms, psychotic symptoms, and social functioning, and (2) investigate whether relations are similar in individuals with and without PD. We estimated an undirected network model in a sample of 504 PD, 572 familial risk for psychosis (FR), and 337 typical comparisons (TC), with a mean age of 34.9 years. Symptoms were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (SFS; 7 nodes). We identified statistically significant differences between the FR and PD samples in global strength (P < .001) and network structure (P < .001). Our results show autistic symptoms (social interaction nodes) are negatively and more closely related to social functioning (withdrawal, interpersonal behavior) than psychotic symptoms. More and stronger connections between nodes were observed for the PD network than for FR and TC networks, while the latter 2 were similar in density (P = .11) and network structure (P = .19). The most central items in strength for PD were bizarre experiences, social skills, and paranoia. In conclusion, specific autistic symptoms are negatively associated with social functioning across the psychosis spectrum, but in the PD network symptoms may reinforce each other more easily. These findings emphasize the need for increased clinical awareness of comorbid autistic symptoms in psychotic individuals.

Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study.

BACKGROUND: Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls. METHODS: Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals. RESULTS: We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters. LIMITATIONS: A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%). CONCLUSION: Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.

Affective dysfunctions in adolescents at risk for psychosis: emotion awareness and social functioning.

Studies of individuals at ultra high risk (UHR) for psychosis have revealed deviations in cognitive and neural development before the onset of psychosis. As affective impairments are among the core dysfunctions in psychotic disorders such as schizophrenia, this study assessed emotion processing and the relationship with social competence in adolescents at risk for psychosis. Thirty-four adolescents at UHR for psychosis and twenty-three non-clinical controls completed the Bermond-Vorst Alexithymia Questionnaire, a measure of emotion awareness. Social inadequacy was measured using the Dutch Personality Questionnaire. Schizophrenia spectrum psychopathology was assessed using self-report and clinical instruments. The Wechsler Adult Intelligence Scale (WAIS) was used to evaluate intellectual functioning. UHR adolescents showed difficulties in identifying and verbalizing their own emotions, independent of intelligence scores. Emotion awareness problems were related to social inadequacy and schizotypal traits in the high risk group. These findings suggest that UHR adolescents may have reduced emotion awareness, independent of intellectual functioning. The relationship with social inadequate behavior fits with the idea that emotion awareness is a prerequisite for the regulation of emotions in social contexts. In the search for early vulnerability markers of risk for psychosis, studying emotion processing besides cognitive abilities might increase our understanding of 'at risk' developmental pathways.

The Attenuated Psychosis Syndrome and Facial Affect Processing in Adolescents With and Without Autism.

BACKGROUND: Autism and schizophrenia spectrum disorders both represent severely disabling neurodevelopmental disorders with marked impairments in social functioning. Despite an increased incidence of psychosis in autism, and substantial overlap in symptoms and cognitive markers, it is unclear whether such phenotypes are specifically related to risk for psychosis or perhaps reflect more general, idiosyncratic autism traits. The attenuated psychosis syndrome (APS) is primarily defined by the presence of attenuated psychotic symptoms, which currently constitute the best and most-replicated clinical predictors of psychosis, and are common in clinical youth with and without autism. The aims of this study were to test the hypothesis that facial affect processing is impaired in adolescents with APS and to explore whether such deficits are more indicative of psychotic or autistic phenotypes on a categorical and dimensional level. MATERIALS AND METHOD: Fifty-three adolescents with APS and 81 typically developing controls (aged 12-18) were included. The APS group consisted of adolescents with (n = 21) and without (n = 32) a diagnosis of autism spectrum disorder. Facial affect recognition was assessed with the Amsterdam Neuropsychological Tasks using a cascade model of cognitive processing, in which disturbances in "lower-level" cognitive abilities (pattern recognition), affect "higher-level" cognitive processes (face recognition and facial affect recognition). For associations with schizotypal and autistic-like traits the Schizotypal Personality Questionnaire and Social Communication Questionnaire were used in a confirmatory item factor analysis framework. RESULTS: Contrary to expectation, APS in adolescents was not associated with impairments in pattern, face, or facial affect recognition. However, the APS group with autism spectrum disorder showed a general latency in response time to social and non-social stimuli. Dimensionally assessed schizotypal and autistic-like traits did not predict the accuracy or the speed of face or facial affect recognition. CONCLUSION: Facial affect processing performance was not associated with APS in adolescence and represents an unlikely early vulnerability marker for psychosis. APS individuals with a more autistic-like profile were characterized by slower responses to social- and non-social stimuli, suggesting that the combined effect of APS and autism spectrum disorder on cognition is larger than for APS alone.

Autism Symptoms, Executive Functioning and Academic Progress in Higher Education Students.

Many students with autism spectrum disorders (ASDs) attending higher education drop out prematurely. The predictive value of self-reported daily executive functioning (EF) and (cognitive) performance-based EF (mental flexibility and working memory) for academic progress was evaluated in 54 young adults with ASD (Mage = 22.5, SD = 2.4, 72% male). Regression analyses showed that autism symptom severity explained 12% of variance in academic progress, which was raised to 36% by adding self-reported daily EF, and to 25% by adding performance-based EF. It is suggested that EF is a candidate marker for academic progress in higher education students with ASD and a candidate target for early intervention.

Educating parents to improve parent-child interactions: Fostering the development of attentional control and executive functioning.

BACKGROUND: Parent-child interaction is essential in the development of attentional control (AC) and executive functioning (EF). Educating parents in AC and EF development may help them to respond more adaptively to their child's developmental needs. AIM: This study aimed to investigate whether parents can be educated to improve interactions with their child through a compact psycho-educational programme that focuses on fostering the development of AC and EF. SAMPLE: Parents and their children in a low-risk sample of four- to eight-year-olds were randomly assigned to either the educational programme condition (N = 34) or the control condition (N = 36). METHODS: Parental supportive presence and intrusiveness were observed during home visits, and children's performance-based AC and EF were assessed before and after the four-session programme. RESULT: Parents in the educational programme improved significantly in support ( η p 2  = .19) and intrusiveness ( η p 2  = .09) compared to controls. There was no short-term programme mediation effect on child AC and EF through parental support and intrusiveness. This study showed, however, that parents who improved after the educational programme had children who improved on AC and EF. CONCLUSION: Parent-child interaction can be enhanced in a low-risk sample of four- to eight-year-olds using a compact educational group programme within the school community. Future studies should aim at examining variations in programme responsiveness and assessing associations between parent-child interaction and AC and EF over time.

Social Attention and Emotional Responsiveness in Young Adults With Autism.

Children with autism spectrum disorder (ASD) are generally characterized by marked impairments in processing of social emotional information, but less is known about emotion processing in adults with the disorder. This study aimed to address this by collecting data on social attention (eye tracking), emotional arousal (skin conductance level, SCL), and emotional awareness (self-report) in a paradigm with social emotional video clips. Fifty-two young, intelligent adults with ASD (IQrange = 88-130, Agerange = 18-24) and 31 typically developing (TD) ASD (IQrange = 94-139, Agerange = 19-28) gender matched controls participated and reported on severity of autism symptoms [Social Responsiveness Scale for Adults (SRS-A)]. Results showed no group difference in social attention, while autism symptom severity was related to decreased attention to faces across participants (r = -.32). Average SCL was lower in the ASD group, but no group difference in arousal reactivity (change from baseline to emotional phases) was detected. Lower SCL during video clips was related to autism symptom severity across participants (r = -.29). ASD individuals reported lower emotional awareness. We conclude that, even though no deviations in social attention or emotional reactivity were found in ASD, an overall lower level of social attention and arousal may help explain difficulties in social functioning in ASD.

Emotional Arousal During Social Stress in Young Adults With Autism: Insights From Heart Rate, Heart Rate Variability and Self-Report.

In order to better understand which factors play a role in non-adaptive social behavior in autism spectrum disorder (ASD) we looked into physiological arousal and awareness of one's own emotions. Heart rate (HR) and heart rate variability (HRV) were measured during a public speaking task in 51 young adults with ASD and 28 typically developing (TD) controls. The results showed no significant group differences in baseline HR/HRV, HR reactivity (change from baseline to the speaking task) or self-reported emotional awareness. However, adults with ASD showed significantly lower HRV reactivity (p = .023, d = 0.6) compared to TD adults. These results suggest a mismatch between arousal regulation and emotional awareness, which may be related to problems in social adaptation in ASD.

Impairments in cognitive empathy and alexithymia occur independently of executive functioning in college students with autism.

Reduced empathy and alexithymic traits are common across the autism spectrum, but it is unknown whether this is also true for intellectually advanced adults with autism spectrum disorder. The aim of this study was to examine whether college students with autism spectrum disorder experience difficulties with empathy and alexithymia, and whether this is associated with their cognitive levels of executive functioning. In total, 53 college students with autism spectrum disorder were compared to a gender-matched group of 29 neurotypical students on cognitive and affective dimensions of empathy and alexithymia. In addition, cognitive performance on executive functioning was measured with computerized and paper-and-pencil tasks. The autism spectrum disorder group scored significantly lower on cognitive empathy and higher on cognitive alexithymia (both d = 0.65). The difference on cognitive empathy also remained significant after controlling for levels of cognitive alexithymia. There were no group differences on affective empathy and alexithymia. No significant relations between executive functioning and cognitive alexithymia or cognitive empathy were detected. Together, these findings suggest that intellectually advanced individuals with autism spectrum disorder experience serious impairments in the cognitive processing of social-emotional information. However, these impairments cannot be attributed to individual levels of cognitive executive functioning.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study.

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain aging. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( ß = -0.60, p corrected < 0.001) and HR-well ( ß = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( ß = -0.24 years, p corrected = 0.06).   Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Individualized Prediction of Transition to Psychosis in 1,676 Individuals at Clinical High Risk: Development and Validation of a Multivariable Prediction Model Based on Individual Patient Data Meta-Analysis.

Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage. Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms ("ultra high risk" OR "clinical high risk" OR "at risk mental state") AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation. Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell's C-statistic 0.655, 95% confidence interval (CIs), 0.627-0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.

Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation.

OBJECTIVE: The dopamine transporter (DAT1) gene has been implicated in attention-deficit/hyperactivity disorder (ADHD), although the mechanism by which it exerts its effects remains unknown. The polymorphism associated with ADHD has been shown to affect expression of the transporter in vitro and in vivo. Dopamine transporters are predominantly expressed in the striatum, but also in the cerebellar vermis. Stimulant medication is often effective in ADHD and is believed to exert its effects by blocking dopamine transporters in the striatum. We set out to investigate the effect of the DAT1 genotype in ADHD in a small, preliminary study. We hypothesized that the DAT1 genotype would affect brain activation patterns in a manner similar to that of stimulant medication, with the lesser expressing allele mirroring its effects. METHOD: We investigated DAT1 gene effects on brain activation patterns in an all-male sample of sibling pairs discordant for ADHD (n = 20) and controls (n = 9). All of the subjects participated in a functional magnetic resonance imaging session using a go/no-go paradigm and provided a DNA sample for analysis. RESULTS: DAT1 genotype affected activation in the striatum and cerebellar vermis. The genotype interacted with familial risk of ADHD in the striatum but not the vermis. CONCLUSIONS: These preliminary results suggest that the DAT1 gene effects in the striatum are involved in translating the genetic risk of ADHD into a neurobiological substrate. As such, this study represents a first step in elucidating the neurobiological mechanisms underlying genetic influences in ADHD. Furthermore, these results may contribute to long-term possibilities for the development of new treatments: If the DAT1 genotype has differential effects on striatal activation, then it may be useful as a surrogate endpoint in individualized treatments targeting genotype/functional magnetic resonance imaging activation profiles.

Linking Parenting and Social Competence in School-Aged Boys and Girls: Differential Socialization, Diathesis-Stress, or Differential Susceptibility?

Girls generally demonstrate superior skill levels in social competence compared to boys. The exact relations of parenting with these gender differences are currently unclear. Gender differences may occur due to exposure to different parenting strategies (differential socialization model) or due to a different impact of similar parenting strategies for boys and girls (differential susceptibility and diathesis-stress model). Objective: In this study we assessed both hypotheses using a multi-method multi-informant approach. We investigated (1) to what extent different parenting strategies mediate the relation between gender and social competence and (2) whether gender and age moderate the relation between parenting strategies and social competence. Design: Parenting strategies were observed during home visits and social competence was assessed using parent and teacher questionnaires and performance-based neurocognitive tasks (N = 98, aged 4 to 8). Results: (1) Parenting strategies did not mediate the relation between gender and social competence. (2) Gender moderated the association between parental questioning style and children's level of social competence: parents asking fewer questions was associated with poorer social cognitive skills in boys only. Parental supportive presence and intrusiveness were related to aspects of social competence irrespective of gender. Age moderated the relation between parenting and aspects of social competence, though in various (unexpected) directions. Conclusion: Our findings do not support the differential socialization hypothesis and provide partial evidence for a diathesis-stress model as an explanation for parental influence on gender differences in social competence.