Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Social network position, trust behavior, and neural activity in young adolescents.

Our social interactions take place within numerous social networks, in which our relationships with others define our position within these networks. In this study, we examined how the centrality of positions within social networks was associated with trust behavior and neural activity in 49 adolescents (Mage = 12.8 years, SDage = 0.4 years). The participants played a trust game with a cartoon animation as a partner, which showed adaptive behavior in response to the participant and was generally untrustworthy. Social network positions were obtained in secondary school classrooms where the participants and their classmates reported on who their friends were. Using social network analysis, a score was calculated that indicated the centrality of everyone's position within the friendship network. The results showed that more central social network positions were associated with higher levels of initial trust behavior, although no evidence was found for a relationship between network position and the adaptation of trust behavior. The results of the functional MRI analyses showed that the centrality of the network positions was positively associated with caudate activity when making trust decisions. Furthermore, the adolescents with more central network positions also showed stronger increases of caudate activity when the partner's return was processed compared to the adolescents with less central network positions. The current study provides initial evidence that social network positions in friendship networks relate to socio-cognitive behavior and neural activity in adolescents.

Increased interference from conflicting perspectives and gender differences: A longitudinal study during adolescence.

Adolescents need to develop adequate perspective-taking skills to successfully navigate their increasingly complex social environments. This study investigated adolescents' development of the cognitive processes of egocentric and altercentric interference that influence perspective-taking abilities. Using the Dot Perspective Task, participants' (N = 803; 50.9% female) egocentric and altercentric interference was measured during 3 consecutive years from 12 to 14 years of age. Linear mixed model analyses showed that whereas overall task performance improved over time, egocentric and altercentric interference increased over time. These results suggest that perspective taking develops at slower rates when there are conflicting perspectives than in situations with no conflict. Moreover, we found that girls showed less egocentric interference than boys. This result provides task-based evidence that supports previous findings of higher self-reported perspective taking in adolescent girls than in adolescent boys.

The Effect of Relative Pubertal Maturation and Perceived Popularity on Symptoms of Depression and Social Anxiety in Adolescent Boys and Girls.

Research has shown that adolescents - particularly girls - who mature relatively early often experience more internalizing problems. This effect is thought to be partially driven by psychosocial mechanisms, but previous research based relative pubertal maturation on complete samples or population standards, instead of considering the adolescents' direct peer environment. In the current study the level of adolescents' pubertal development was assessed relative to their classmates in order to examine relative pubertal maturation. The effects of adolescents' relative pubertal status, and their perceived popularity, on symptoms of social anxiety and depression in adolescents were studied. All analyses were also performed for absolute pubertal maturation. Participants were 397 young adolescents (Mage = 13.06, SD = 0.36, 49.9% girls) at timepoint 1, and 307 (Mage = 14.08, SD = 0.36, 50.5% girls) at timepoint 2. A significant positive relationship was found between relative pubertal timing and symptoms of depression for girls but not boys. Social anxiety symptoms were not significantly related to relative pubertal timing in either sex. Relative pubertal maturation had no effect on change in or persistence of depressive and social anxiety symptoms one year later. The effects of the comparison with the immediate peer environment, did not seem to explain more variance in internalizing symptoms than the effects of early maturation.

A Few Close Friends? Adolescent Friendships' Effect on Internalizing Symptoms Is Serially Mediated by Desire for More Friends and Social Goal Orientation.

Interpersonal connection is a fundamental human motivation, and the extent to which it is fulfilled is a strong predictor of symptoms of internalizing disorders such as social anxiety and depression, perhaps especially during the "social reorienting" period of adolescence. However, little is known about the contribution to this effect of the individual's social motivations, which are intensified during adolescence. Furthermore, social goal orientation - an individual's priorities and intentions in social interactions - is an important predictor of vulnerability to internalizing symptoms. Adolescents spend most of their waking lives in classrooms, bounded social networks with a limited pool of candidates for befriending. This study investigated whether friendships within one's class protects against internalizing symptoms in part by reducing the desire for more classmate friendships, which may tend to promote maladaptive social goals. Participants were 423 young adolescents (M age = 13.2, sd = 0.52 years; 49.4% girls). As predicted, adolescents' number of reciprocated classroom friendships had a protective effect on internalizing symptoms which was serially mediated by desire for more such friendships, and social goal orientation. However, only demonstration-avoidance goals significantly predicted internalizing symptoms. Unreciprocated friendship nominations were unexpectedly associated with stronger desire and more social anxiety symptoms. The results suggest that the effect of number of friends is mediated by the individual's thoughts and feelings about their number of friendships, such that a strong desire for more friendships promotes maladaptive goals, oriented toward social status and consequently less oriented toward the cultivation of interpersonal intimacy with the friends they already have.

Development of the neural correlates of self- and other-referential processing across adolescence.

During adolescence, major changes in brain mechanisms take place and differentiated representations of both the self and of others are developed. Although studies have investigated the neural mechanisms of self- and other-referential processing in adolescents, the development of these mechanisms remain largely unaddressed. Here, we report a three-year longitudinal study with annual measurements, and investigate the developmental trajectories of activity and connectivity underlying self- and other-referential processes in 34 participants from early to mid-adolescence (mean age timepoints 1, 2, 3 = 12.9, 13.9, 15.0 years). Moreover, we probe whether these correlates continue to develop from mid-adolescence to young adulthood by comparing neural correlates of the adolescents at the last measurement to an independent group of 42 young adults (mean age 22 years). Participants underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar peer. Brain activity within the dorsal medial prefrontal cortex (dMPFC) and right temporal parietal junction (TPJ) showed a quadratic change from early to mid-adolescence, with a peak in activity at the second measurement when evaluating the self, the similar and dissimilar peer. No differential activity was observed when comparing the adolescents to young adults. Functional connectivity did not change from early to mid-adolescence, however, connectivity of the dMPFC with a posterior midline region during self- and other-referential processing relative to the control condition reduced from mid-adolescence to young adulthood. Together, these findings provide insight in the developmental trajectories of brain activity and connectivity underlying the development of the self-concept and representations of peers in adolescence.

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Exploring the association between social behaviour, trust, and its neural correlates in first episode psychosis patients and in individuals at clinical high risk for psychosis.

OBJECTIVES: Psychosis is characterized by paranoid delusions, social withdrawal, and distrust towards others. Trust is essential for successful social interactions. It remains unknown which aspects of social functioning are associated with reduced trust in psychosis. Therefore, we investigated the association between social behaviour, trust, and its neural correlates in a group of individuals with psychotic symptoms (PS-group), consisting of first episode psychosis patients combined with individuals at clinical high risk. METHODS: We compared 24 PS individuals and 25 healthy controls. Affect and social withdrawal were assessed using the Experience Sampling Method. Trust was measured during functional magnetic resonance imaging (fMRI) scanning, using a trust game with a cooperative and unfair counterpart. RESULTS: The PS-group showed lower baseline trust compared to controls and reported less positive and more negative general affect. Social withdrawal did not differ between the groups. Social withdrawal and social reactivity in affect (i.e., changes in affect when with others compared to when alone) were not associated with trust. On the neural level, in controls but not in the PS-group, social withdrawal was associated with caudate activation during interactions with an unfair partner. An increase in positive social reactivity, was associated with reduced insula activation in the whole sample. CONCLUSIONS: Social withdrawal and social reactivity were not associated with reduced initial trust in the PS-group. Like controls, the PS-group showed a positive response in affect when with others, suggesting a decrease in emotional distress. Supporting patients to keep engaging in social interactions, may alleviate their emotional distress. PRACTITIONER POINTS: Individuals with psychotic symptoms show reduced initial trust towards unknown others. Trust in others is not associated with social withdrawal and reported affect when with others, nor when alone. Like controls, individuals with psychotic symptoms showed reduced negative affect and increased positive affect when with others compared to when alone. We emphasize to support individuals with psychotic symptoms to keep engaging in social interactions, given it may reduce social withdrawal and alleviate their emotional distress.

Emotion Recognition and Inhibitory Control in Adolescent Players of Violent Video Games.

Developmental changes during adolescence may make youth susceptible to violent media effects. Two studies with male adolescents (N1 = 241; N2 = 161; aged 12-17) examined how habitual and short-term violent video gaming may affect emotion recognition and inhibitory control. We found that not habitual exposure to violent video games, but to antisocial media content predicted worse emotion recognition. Furthermore, higher habitual exposure to violent games predicted better inhibitory control over emotional stimuli in a stop signal task. However, short-term causal effects of violent gameplay on adolescents were not found. While these results do not indicate a negative impact of violent video games on young players, future research may further investigate possible effects of antisocial media content on adolescents.

Students' beliefs about the nature of intelligence (mindset).

Important adolescents' career-related decisions might be influenced by their beliefs about malleability of intelligence and learning (mindset). We combined quantitative and qualitative data to provide in-depth insights in the beliefs that 13-14-year-olds hold about learning and intelligence, the factors influencing these beliefs, and the consequences of these beliefs in relation to classroom behaviour and study choices. To establish students' mindsets quantitatively, we categorised theory of intelligence questionnaire (TOI; Dweck, 1999) averaged scores into three levels: entity, intermediate or incremental mindsets, to provide insight into the distribution of the different mindset types in our sample (N = 492). The results of this quantitative study show that more than half of the students believed intelligence is "fixed" (entity mindset), these data showed no effect of gender. To gain more in-depth insight in the views of these students, focus groups about mindset and its influences and consequences were held in a subsample (n = 176). The qualitative data provide more nuanced insights, for example they reveal subtle gender differences regarding effort beliefs and motivation. Integrated discussion of the quantitative and qualitative results demonstrates that this multi-method approach reflects the complexity of the concept mindset better than only the widely used TOI questionnaire.

Understanding urbanicity: how interdisciplinary methods help to unravel the effects of the city on mental health.

Twenty-first century urbanization poses increasing challenges for mental health. Epidemiological studies have shown that mental health problems often accumulate in urban areas, compared to rural areas, and suggested possible underlying causes associated with the social and physical urban environments. Emerging work indicates complex urban effects that depend on many individual and contextual factors at the neighbourhood and country level and novel experimental work is starting to dissect potential underlying mechanisms. This review summarizes findings from epidemiology and population-based studies, neuroscience, experimental and experience-based research and illustrates how a combined approach can move the field towards an increased understanding of the urbanicity-mental health nexus.

Neural correlates of self- and other-referential processing in young adolescents and the effects of testosterone and peer similarity.

During adolescence, self-concept develops profoundly, accompanied by major changes in hormone levels. Self-evaluations become more complex, and peers and their opinions increasingly salient. Neuroimaging studies have investigated self- and other-related processing in adolescents, however, the influence of similarity of peers on these processes is still unclear, as well as functional connectivity underlying such processes. We investigated the effect of peer similarity on neural activity and connectivity underlying self- and other-referential processing, by distinguishing between a similar and dissimilar peer when making other-evaluations. Moreover, we explored the association between testosterone and brain activity during self-evaluations. Sixty-six young adolescents underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar classmate. The ventral medial prefrontal cortex (MPFC) showed increased engagement in self-referential processing, and the posterior cingulate cortex and right temporal parietal junction during other-evaluations. However, activity did not differ between the similar and dissimilar other conditions. Functional connectivity of the ventral MPFC included the striatum when evaluating the similar peer and frontoparietal regions when evaluating the dissimilar peer. Furthermore, inter-individual differences in testosterone levels were positively associated with dorsal MPFC activity in males. This study provides insight into the influence of peer similarity on activity and connectivity underlying other-referential processing in young adolescents, and suggests that testosterone affects neural correlates of self-referential processing.

Trust and the city: Linking urban upbringing to neural mechanisms of trust in psychosis.

OBJECTIVE: Elevated prevalence of non-affective psychotic disorders is often found in densely populated areas. This functional magnetic resonance imaging study investigates if reduced trust, a component of impaired social functioning in patients with psychotic disorder, is associated with urban upbringing. METHODS: In total, 39 patients (22 first episode and 17 clinical high risk) and 30 healthy controls, aged 16-29, performed two multi-round trust games, with a cooperative and unfair partner during functional magnetic resonance imaging scanning. Baseline trust was operationalized as the first investment made, and changes of trust as changes in investments made over the 20 trials during the games. Urban exposure during upbringing (0-15 years) was defined as higher urban (≥2500 inhabitants/km2) or lower urban (<2500 inhabitants/km2). RESULTS: Patients displayed lower baseline trust (first investment) than controls, regardless of urbanicity exposure. During cooperative interactions, lower-urban patients showed increasing investments. In addition, during cooperative interactions, group-by-developmental urbanicity interactions were found in the right and left amygdalae, although for the latter only at trend level. Higher urbanicity was associated with decreased activation of the left amygdala in patients and controls during investments and with increased activation of the right and left amygdalae in patients only, during repayments. During unfair interactions, no associations of urbanicity with behavior or brain activation were found. CONCLUSION: Urban upbringing was unrelated to baseline trust. Associations with urbanicity were stronger for patients compared to controls, suggesting greater susceptibility to urbanicity effects during the developmental period. Higher-urban patients failed to compensate for the initial distrust specifically during repeated cooperative interactions. This finding highlights potential implications for social functioning. Urban upbringing was linked to differential amygdala activation, suggesting altered mechanisms of feedback learning, but this was not associated with trust game behavior.

The effect of social feedback from peers on adolescent cognitive control.

INTRODUCTION: Social feedback can influence cognitive control during adolescence, particularly if provided by peers. The main aim of this study was to investigate if feedback given by liked or disliked peers differentially influenced adolescents' cognitive control. The second aim was to investigate if these effects could be linked to the participants' social embeddedness in their classroom. METHODS: A personalized incentive go/no-go task was administered to 45 early adolescents (M = 11.6 years, 25 male) and 68 late adolescents (M = 16.7, 38 male) in the Netherlands. Feedback was given after no-go trials in two social feedback conditions (displaying a picture of a real liked or disliked classmate) and in a non-social control condition. RESULTS: Performance on the task significantly improved with age. We found no differences between conditions in cognitive control, as measured by d-prime. However, analysis of task speed revealed slower reaction times during the liked peer condition as compared to the disliked peer and the control condition, potentially suggesting that participants responded more cautiously, or alternatively that participants were more distracted. These effects did not differ between age groups. Participants' differences in task performance were not reflected in their social embeddedness in the classroom. CONCLUSIONS: This study shows that the same kind of social feedback can have different effects on adolescent behaviour depending on the peer delivering the feedback. It demonstrates the importance of studying the effects of real life social environments to better understand and utilize their impact on adolescent development.

The Teenage Brain: Public Perceptions of Neurocognitive Development during Adolescence.

Over the past decade, important insights have been obtained into the neurocognitive development during adolescence. To better understand how these neuroscientific insights impact the real world, we investigated how neuroscience has shaped public perceptions of the "teenage brain" and if these perceptions influence adolescent behavior. When asking to generate free associations with the word "teenage brain," adolescents ( n = 363, Mage = 14.47 years) and parents ( n = 164, Mage = 47.16 years) more often mention undesirable behaviors (e.g., "irresponsible") than desirable behaviors (e.g., "creative"). Despite these dominantly negative associations, priming adolescents with positively versus negatively framed statements about adolescent brain development did not influence their subsequent risk-taking, impulsivity, and performance on response-to-failure tasks. However, we did find a more nuanced effect, related to how much adolescents agreed with the negative versus positive priming statements: Adolescents' negative beliefs about adolescent brain development reinforced negative behaviors by increased risk-taking behaviors, and adolescents' positive beliefs reinforced positive behaviors by using positive strategies to cope with academic setbacks. The current findings underline the impact of views that build up over time and that these are not easily influenced by a one-time instance of information but rather reinforce the impact of new information. To prevent negative perceptions of the teenage brain from becoming self-fulfilling prophecies, it is important that communication about adolescent neurocognitive development is framed in a more balanced way. Neuroscientists need to be more aware of how their research impacts the real world, before we are fully ready for "real-world neuroscience."

Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk.

BACKGROUND: Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust. METHODS: Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games. RESULTS: Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity. CONCLUSIONS: Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.

Elementary school children's associations of antisocial behaviour with risk-taking across 7-11 years.

BACKGROUND: The impact of childhood antisocial behaviour on future maladaptation has been acknowledged. Risk-taking has been associated with antisocial behaviour in adolescents and adults, but its association with childhood antisocial behaviour is understudied. In this study, we explored the association of children's risk-taking with antisocial behaviour in mainstream elementary schoolchildren studied longitudinally across 7-11 years. METHODS: One thousand and eighty-six children (51% boys) were assessed in three annual waves. Antisocial behaviours (aggressive, covert antisocial and oppositional defiant behaviour) were assessed using teacher- and peer-reports. Risk-taking was measured using the Balloon Analogue Risk Task (BART). The association of antisocial behaviour with risk-taking was analysed using parallel growth models. RESULTS: Children with higher levels of risk-taking at age 7 showed increased growth in peer-reported aggression from age 7 to 11. Risk-taking, that is increased levels at age 7 in boys and increased growth in girls, predicted increased growth in peer-reported oppositional defiant behaviour. Associations of risk-taking with teacher-reported aggression and covert antisocial behaviour were at trend level. CONCLUSIONS: Results indicated that already in childhood, among typically developing children, risk-taking is associated with the development of antisocial behaviour. Future research focused on antisocial behaviour, but also school mental health workers and clinicians should take into account that already in childhood, risk-taking might affect antisocial behaviour development.

Metacognitive training in patients recovering from a first psychosis: an experience sampling study testing treatment effects.

Cognitive biases, negative affect and negative self-esteem are associated with paranoia in people with psychotic disorders. Metacognitive group training (MCT) aims to target these biases although research has shown mixed results. Our objective was to establish the effect of MCT on paranoid ideation in patients with recent onset psychosis in a powerful experience sampling design. 50 patients between the age of 18 and 35 were included in a single-blind, parallel group RCT comparing MCT with occupational therapy (OT) as an active control condition. We assessed via questionnaires and experience sampling treatment effects on paranoid ideation, delusional conviction, the cognitive bias jumping to conclusion (JTC), and cognitive insight, as well as treatment effects on associations between negative affect, negative self-esteem and paranoid ideation. Patients in the MCT group did not show a decrease in paranoid ideation, delusional conviction, JTC-bias or an increase in cognitive insight compared with OT. However, negative affect showed a weaker association with paranoid ideation post-treatment in the MCT condition. In the OT condition, this association was stronger post-treatment. We tentatively suggest that patients with an early psychosis seemed to benefit from MCT in emotional learning compared with the OT condition. Despite the fact that the group training is well-received by patients, subsequent individual MCT (MCT+) may be indicated for stronger favorable effects on paranoid ideation.

The effect of childhood trauma and Five-Factor Model personality traits on exposure to adult life events in patients with psychotic disorders.

INTRODUCTION: Recent life events are associated with transition to and outcome in psychosis. Childhood trauma and personality characteristics play a role in proneness to adult life events. However, little is known about the relative contribution and interrelatedness of these characteristics in psychotic disorders. Therefore, we investigated whether Five-Factor Model (FFM) personality traits and childhood trauma (abuse and neglect) predict adult life events, and whether the effect of childhood trauma on life events is mediated by personality traits. METHOD: One hundred and sixty-three patients with psychotic disorders were assessed at baseline on history of childhood maltreatment and FFM personality traits, and on recent life events at 3-year follow-up. RESULTS: Childhood abuse is associated with negative life events, and part of the effect of childhood abuse on negative life events is mediated by openness to experience. Openness to experience and extraversion are associated with more positive and negative life events. Childhood neglect and lower extraversion are related to experiencing less positive events. CONCLUSION: The association between childhood trauma and recent life events is partly mediated by personality. Future research could focus on mechanisms leading to positive life events, as positive life events may buffer against development of mental health problems.