Brain network connectivity during peer evaluation in adolescent females: Associations with age, pubertal hormones, timing, and status.

Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9-15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal - Reward and Cinguloopercular - Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal - Reward connectivity was only associated with hormones. Finally, Cinguloopercular - Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Development and Validation of the Negative Symptom Inventory-Psychosis Risk.

BACKGROUND AND HYPOTHESES: Early identification and prevention of psychosis is limited by the availability of tools designed to assess negative symptoms in those at clinical high-risk for psychosis (CHR). To address this critical need, a multi-site study was established to develop and validate a clinical rating scale designed specifically for individuals at CHR: The Negative Symptom Inventory-Psychosis Risk (NSI-PR). STUDY DESIGN: The measure was developed according to guidelines recommended by the NIMH Consensus Conference on Negative Symptoms using a transparent, iterative, and data-driven process. A 16-item version of the NSI-PR was designed to have an overly inclusive set of items and lengthier interview to support the ultimate intention of creating a new briefer measure. Psychometric properties of the 16-item NSI-PR were evaluated in a sample of 218 CHR participants. STUDY RESULTS: Item-level analyses indicated that men had higher scores than women. Reliability analyses supported internal consistency, inter-rater agreement, and temporal stability. Associations with measures of negative symptoms and functioning supported convergent validity. Small correlations with positive, disorganized, and general symptoms supported discriminant validity. Structural analyses indicated a 5-factor structure (anhedonia, avolition, asociality, alogia, and blunted affect). Item response theory identified items for removal and indicated that the anchor range could be reduced. Factor loadings, item-level correlations, item-total correlations, and skew further supported removal of certain items. CONCLUSIONS: These findings support the psychometric properties of the NSI-PR and guided the creation of a new 11-item NSI-PR that will be validated in the next phase of this multi-site scale development project.

Negative Symptom Inventory-Self-Report (NSI-SR): Initial development and validation.

Negative symptoms (i.e., anhedonia, avolition, asociality, blunted affect, alogia) are frequently observed in the schizophrenia-spectrum (SZ) and associated with functional disability. While semi-structured interviews of negative symptoms represent a gold-standard approach, they require specialized training and may be vulnerable to rater biases. Thus, brief self-report questionnaires measuring negative symptoms may be useful. Existing negative symptom questionnaires demonstrate that this approach may be promising in schizophrenia, but no measure has been devised for use across stages of psychotic illness. The present study reports initial psychometric validation of the Negative Symptom Inventory-Self-Report (NSI-SR), the self-report counterpart of the Negative Symptom Inventory-Psychosis Risk clinical interview. The NSI-SR is a novel transphasic negative symptoms measure assessing the domains of anhedonia, avolition, and asociality. The NSI-SR and related measures were administered to two samples: 1) undergraduates (n = 335), 2) community participants, including: SZ (n = 32), clinical-high risk for psychosis (CHR, n = 25), and healthy controls matched to SZ (n = 31) and CHR (n = 30). The psychometrically trimmed 11-item NSI-SR showed good internal consistency and a three-factor solution reflecting avolition, asociality, and anhedonia. The NSI-SR demonstrated convergent validity via moderate to large correlations with clinician-rated negative symptoms and related constructs in both samples. Discriminant validity was supported by lower correlations with positive symptoms in both samples; however, correlations with positive symptoms were still significant. These initial psychometric findings suggest that the NSI-SR is a reliable and valid brief questionnaire capable of measuring negative symptoms across phases of psychotic illness.

Social goals in girls transitioning to adolescence: associations with psychopathology and brain network connectivity.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

Individual differences in frontal alpha asymmetry moderate the relationship between acute stress responsivity and state and trait anxiety in adolescents.

Stress is a risk factor in the development and maintenance of psychopathology, particularly anxiety. Despite theory suggesting differences in stress responsivity may explain heterogeneity in anxiety, findings remain contradictory. This may be due to failure to account for individuals' neurobiological states and outdated methodologic analyses which confound conceptually and biologically distinct stress response pathways. In 145 adolescents, this study examined whether individual differences in neural activation underlying motivational states, indexed by resting frontal alpha asymmetry (FAA) before and after the Trier Social Stress Test (TSST), moderate the relationship between stress responsivity (measured by cortisol) and anxiety. Adolescents with rightward FAA activation (indexed by changes in resting FAA pre-to-post TSST) and high trait anxiety showed blunted cortisol reactivities while those with leftward FAA activation and high state anxiety showed prolonged cortisol recoveries. Our work reveals individual differences in vulnerability to psychosocial stressors and is the first study to show that FAA activation moderates the relationships between anxiety and distinct phases of the stress response in adolescents.

Triple Network Functional Connectivity During Acute Stress in Adolescents and the Influence of Polyvictimization.

BACKGROUND: Exposure to both chronic and acute stressors can disrupt functional connectivity (FC) of the default mode network (DMN), salience network (SN), and central executive network (CEN), increasing risk for negative health outcomes. During adolescence, these stress-sensitive triple networks undergo critical neuromaturation that is altered by chronic exposure to general forms of trauma or victimization. However, no work has directly examined how acute stress affects triple network FC in adolescents or whether polyvictimization-exposure to multiple categories/subtypes of victimization-influences adolescent triple network neural acute stress response. METHODS: This functional magnetic resonance imaging study examined seed-to-voxel FC of the DMN, SN, and CEN during the Montreal Imaging Stress Task. Complete data from 73 participants aged 9 to 16 years (31 female) are reported. RESULTS: During acute stress, FC was increased between DMN and CEN regions and decreased between the SN and the DMN and CEN. Greater polyvictimization was associated with reduced FC during acute stress exposure between the DMN seed and a cluster containing the left insula of the SN. CONCLUSIONS: These results indicate that acute stress exposure alters FC between the DMN, SN, and CEN in adolescents. In addition, FC changes during stress between the DMN and SN are further moderated by polyvictimization exposure.

Coordination of autonomic and endocrine stress responses to the Trier Social Stress Test in adolescence.

Dysregulations in autonomic and endocrine stress responses are linked to the emergence of psychopathology in adolescence. However, most studies fail to consider the interplay between these systems giving rise to conflicting findings and a gap in understanding adolescent stress response regulation. A multisystem framework-investigation of parasympathetic (PNS), sympathetic (SNS), and hypothalamic pituitary adrenal (HPA) axis components and their coordination-is necessary to understand individual differences in stress response coordination which contribute to stress vulnerabilities. As the first investigation to comprehensively evaluate these three systems in adolescence, the current study employed the Trier Social Stress Test in 72 typically developing adolescents (mean age = 13) to address how PNS, SNS, and HPA stress responses are coordinated in adolescence. Hypotheses tested key predictions of the Adaptive Calibration Model (ACM) of stress response coordination. PNS and SNS responses were assessed via heart rate variability (HRV) and salivary alpha amylase (sAA) respectively. HPA responses were indexed by salivary cortisol. Analyses utilized piecewise growth curve modeling to investigate these aims. Supporting the ACM theory, there was significant hierarchical coordination between the systems such that those with low HRV had higher sAA and cortisol reactivity and those with high HRV had low-to-moderate sAA and cortisol responsivity. Our novel results reveal the necessity of studying multisystem dynamics in an integrative fashion to uncover the true mechanisms of stress response and regulation during development. Additionally, our findings support the existence of characteristic stress response profiles as predicted by the ACM model.

Stress-related hippocampus activation mediates the association between polyvictimization and trait anxiety in adolescents.

Early life stress exposures are associated with adverse health outcomes and heightened anxiety symptoms in adolescents. Stress-sensitive brain regions like the hippocampus and amygdala are particularly impacted by early life adversities and are also implicated in the development of anxiety disorders. However, to date, no studies have specifically examined the neural correlates of polyvictimization (exposure to multiple categories of victimization) or the contribution of stress-sensitive neural nodes to polyvictimization's impact on mental health. To elucidate these relationships, the current study analyzed associations between polyvictimization, hippocampal and amygdalar activation during an acute stress task and trait anxiety in a sample of 80 children and adolescents aged 9-16 years (33 female participants). Results showed that polyvictimization was associated with higher trait anxiety as well as greater stress-related right hippocampus activation, and this greater hippocampal activity predicted heightened trait anxiety. Robust mediation analyses revealed that stress-related right hippocampus activation partially mediated the relationship between polyvictimization and trait anxiety. Our results expand upon the existing polyvictimization literature by suggesting a possible neurobiological pathway through which polyvictimization is connected to the etiology of mental illness.

Eveningness chronotype preference among individuals at clinical high risk for psychosis.

BACKGROUND: Circadian rhythm disturbances are frequently implicated in psychosis. Indeed, research has suggested several avenues by which circadian rhythms may play a mechanistic role as well as contribute to clinical outcomes. Despite its potential role as a risk factor, little is known about circadian rhythm disruption among individuals at clinical high risk (CHR) for psychosis, clinical correlates, or specificity to the psychosis risk syndrome. METHODS: Eighty-four CHR, 74 individuals with depressive disorders (DD), and 101 non-psychiatric controls (NPC) participated in structured clinical interviews and provided self-reports of chronotype preference. Clinical (positive, negative, anxious, and depressive symptoms) and social functioning outcomes were self-reported and/or clinician-rated. Analyses of covariance controlling for demographics examined group differences in chronotype preference, and partial Pearson correlations evaluated associations with clinical/functional outcomes. RESULTS: Group differences were observed (F(11, 246) = 8.05, p < .001) with CHR and DD individuals indicating greater eveningness preference compared to NPC. A follow-up sensitivity analysis examining CHR participants with (n = 25) and without (n = 59) depressive disorders indicated no difference in chronotype preference (F(10,72) = 0.00, p = .99). Greater eveningness preference was related to greater negative symptoms (i.e., avolition; r = -0.25) and anxiety (r = -0.34) among CHR individuals. CONCLUSIONS: CHR and DD display greater preference for eveningness chronotype compared to NPC indicating the disruption is associated with a range of mental health concerns, and not specific to the psychosis-risk syndrome. However, comorbidity with DD did not appear to be driving the finding in the CHR group. Further research may examine shared versus non-shared underlying mechanisms contributing to chronotype preference across psychiatric presentations.

Prevalence and Functional Consequences of Social Anxiety in Individuals at Clinical High-Risk for Psychosis: Perspective From a Community Sample Comparison.

BACKGROUND: Social anxiety disorder (SAD) commonly occurs among individuals at clinical high-risk (CHR) for psychosis. Extant research has yet to examine the prevalence and clinical/functional correlates of SAD in this population compared to a community control (CC) sample. This comparison may improve the generalizability that traditional nonpsychiatric control samples cannot provide. Additionally, it remains unknown how SAD contributes to symptom severity and social impairments in individuals at CHR for psychosis. METHODS: Both CHR and CC groups were recruited from general community sources; CC participants were not excluded in this analysis on the basis of any psychopathology except psychosis. A total of 245 adolescents and young adults (CHR = 81; CC = 164) were administered the Social Phobia Scale, the Structured Interview for Psychosis-risk Syndromes, Structured Clinical Interview for DSM-5 Research Version, and the Social Functioning Scale. RESULTS: The CHR group was at increased risk for having SAD relative to CC (42% CHR; 13% CC; RR = 3.28) and, to a lesser degree, a non-SAD anxiety disorder (41% CHR; 29% CC; RR = 1.42). Greater social anxiety was related to higher levels of negative (r = 0.29) but not positive (r = 0.05) symptoms within the CHR group. Furthermore, elevated social anxiety was found to be linked with poor social functioning in the CHR group (r = -0.31). CONCLUSIONS: These findings demonstrate the specificity of SAD over and above other anxiety disorders in individuals at CHR for psychosis and the critical target of SAD to treat subclinical psychotic symptoms and social functioning.

Reprint of: A review of negative symptom assessment strategies in youth at clinical high-risk for psychosis.

Studies attempting to deconstruct the heterogeneity of schizophrenia and the attenuated psychosis syndrome consistently find that negative symptoms are a core dimension that is distinct from other aspects of the illness (e.g., positive and disorganized symptoms). Negative symptoms are also highly predictive of poor community-based functional outcomes, suggesting they are a critical treatment target. Unfortunately, pharmacological and psychosocial treatments for negative symptoms have demonstrated limited effectiveness. To address this critical unmet therapeutic need, the NIMH sponsored a consensus development conference to delineate research priorities for the field and stimulate treatment development. A primary conclusion of this meeting was that next-generation negative symptom rating scales should be developed to address methodological and conceptual limitations of existing instruments. Although second-generation rating scales were developed for adults with schizophrenia, progress in this area has lagged behind for youth at clinical-high risk (CHR) for developing psychosis (i.e. those meeting criteria for a prodromal syndrome). Given that negative symptoms are highly predictive of the transition to diagnosable psychotic illness, enhancing our ability to detect negative symptoms in CHR youth is paramount. The current paper discusses conceptual and methodological limitations inherent to existing scales that assess negative symptoms in CHR youth. The theoretical and clinical implications of these limitations are evaluated. It is concluded that new scales specifically designed to assess negative symptoms in CHR youth are needed to accurately chart mental illness trajectories and determine when, where, and how to intervene. Recent efforts to develop next-generation measures designed specifically for CHR youth to meet this urgent need in the field are discussed. These new approaches offer significant progress for addressing issues inherent to earlier scales.

Neural mechanisms of acute stress and trait anxiety in adolescents.

Adolescence is a critical period of heightened stress sensitivity and elevated vulnerability for developing mental illness, suggesting a possible association between stress exposure and the etiology of psychiatric disorders. In adults, aberrant neurobiological responses to acute stress relate to anxiety symptoms, yet less is known about the neural stress response in adolescents and how it relates to biological and psychological variables. Here we characterize the neurobiology of stress response in adolescents using multiple modalities, including neuroimaging, subjective stress ratings, heart rate, and cortisol data. We evaluated stress response in adolescents using the Montreal Imaging Stress Task (MIST), an acute psychosocial stressor commonly administered in adult functional magnetic resonance imaging (fMRI) studies but not previously utilized with this population. FMRI data were acquired from 101 adolescents (44 female; 9-16 years) exhibiting varied trait anxiety severity. The MIST elicited decreased high-frequency heart rate variability and increased heart rate, subjective stress and cortisol. Whole-brain analyses comparing fMRI activity during experimental versus control MIST conditions revealed stress-related activation in regions including the anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex and deactivations in the hippocampus, ventral striatum, and putamen. Region of Interest analyses found that during acute stress (a) hippocampal deactivation corresponded to heightened cortisol release, (b) trait anxiety was associated with increased hippocampal and ventral striatum activation and decreased putamen activity, and (c) males exhibited greater putamen deactivation than females. These results provide novel evidence that the MIST is an effective stressor for adolescents. Associations between the neural acute stress response, other biological factors, and trait anxiety highlight the importance of these neurobiological mechanisms in understanding anxiety disorders.

Perceived stress influences anhedonia and social functioning in a community sample enriched for psychosis-risk.

Existing animal and human research support the causal role of stress in the emergence of anhedonia, and in turn, the influence of anhedonia in social functioning. However, this model has not been tested in relation to psychosis-risk; this literature gap is notable given that both anhedonia and declining social functioning represent key markers of risk of developing a psychotic disorder such as schizophrenia. The current research tested the evidence for this model using structural equation modeling in 240 individuals selected based on a range of psychosis-risk symptomatology from the general community. Results supported this model in comparison with alternative models, and additionally emphasized the direct role of perceived stress in social functioning outcomes. Findings suggest the clinical relevance of targeting early perceptions of stress in individuals meeting psychosis-risk self-report criteria in an effort to prevent subsequent anhedonia and declines in social functioning.

Altered temporal, but intact spatial, features of transient network dynamics in psychosis.

Contemporary models of psychosis suggest that a continuum of severity of psychotic symptoms exists, with subthreshold psychotic experiences (PEs) potentially reflecting some genetic and environmental risk factors shared with clinical psychosis. Thus, identifying abnormalities in brain activity that manifest across this continuum can shed new light on the pathophysiology of psychosis. Here, we investigated the moment-to-moment engagement of brain networks ("states") in individuals with schizophrenia (SCZ) and PEs and identified features of these states that are associated with psychosis-spectrum symptoms. Transient brain states were defined by clustering "single snapshots" of blood oxygen level-dependent images, based on spatial similarity of the images. We found that individuals with SCZ (n = 35) demonstrated reduced recruitment of three brain states compared to demographically matched healthy controls (n = 35). Of these three illness-related states, one specific state, involving primarily the visual and salience networks, also occurred at a lower rate in individuals with persistent PEs (n = 22), compared to demographically matched healthy youth (n = 22). Moreover, the occurrence rate of this marker brain state was negatively correlated with the severity of PEs (r = -0.26, p = 0.003, n = 130). In contrast, the spatial map of this state appeared to be unaffected in the SCZ or PE groups. Thus, reduced engagement of a brain state involving the visual and salience networks was demonstrated across the psychosis continuum, suggesting that early disruptions of perceptual and affective function may underlie some of the core symptoms of the illness.

Secondary Sources of Negative Symptoms in Those Meeting Criteria for a Clinical High-Risk Syndrome.

BACKGROUND: Negative symptoms are diagnostic characteristics of schizophrenia. They can result from primary (i.e., idiopathic) or secondary (i.e., due to other factors such as depression, anxiety, psychosis, disorganization, medication effects) features of the illness. Although secondary sources of negative symptoms are prevalent among individuals meeting criteria for clinical high-risk syndromes that are due to high rates of comorbidity, the extent to which secondary sources account for variance in negative symptom domains is unknown. Addressing this gap is an important step in informing vulnerability models and treatments for negative symptoms. This study aimed to investigate secondary sources of negative symptoms in those meeting criteria for a clinical high-risk syndrome (N = 192). METHODS: Simultaneous regression and hierarchical partitioning methods were used to determine the proportion of variance explained by selective serotonin reuptake inhibitor use, anxiety, depression, unusual thought content, and disorganized communication in predicting severity of five negative symptom domains (avolition, anhedonia, asociality, blunted affect, and alogia). RESULTS: Findings revealed that depression explained the largest proportion of variance in avolition, asociality, and anhedonia. Anxiety was the most predictive of blunted affect, and selective serotonin reuptake inhibitor use explained the most variance in alogia. Analyses within male and female samples revealed that in males, depression explained a large proportion of variance in several negative symptom domains, while in females, selective serotonin reuptake inhibitor use explained variance in alogia. CONCLUSIONS: Results highlight heterogeneity in variance explained by secondary sources of negative symptoms. These findings guide treatment development for secondary sources of negative symptoms. Furthermore, results inform etiologic models of psychosis and negative symptom conceptualizations.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning.

BACKGROUND: The ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. METHODS: 24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. RESULTS: Previous work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. CONCLUSIONS: These findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

A review of negative symptom assessment strategies in youth at clinical high-risk for psychosis.

Studies attempting to deconstruct the heterogeneity of schizophrenia and the attenuated psychosis syndrome consistently find that negative symptoms are a core dimension that is distinct from other aspects of the illness (e.g., positive and disorganized symptoms). Negative symptoms are also highly predictive of poor community-based functional outcomes, suggesting they are a critical treatment target. Unfortunately, pharmacological and psychosocial treatments for negative symptoms have demonstrated limited effectiveness. To address this critical unmet therapeutic need, the NIMH sponsored a consensus development conference to delineate research priorities for the field and stimulate treatment development. A primary conclusion of this meeting was that next-generation negative symptom rating scales should be developed to address methodological and conceptual limitations of existing instruments. Although second-generation rating scales were developed for adults with schizophrenia, progress in this area has lagged behind for youth at clinical-high risk (CHR) for developing psychosis (i.e. those meeting criteria for a prodromal syndrome). Given that negative symptoms are highly predictive of the transition to diagnosable psychotic illness, enhancing our ability to detect negative symptoms in CHR youth is paramount. The current paper discusses conceptual and methodological limitations inherent to existing scales that assess negative symptoms in CHR youth. The theoretical and clinical implications of these limitations are evaluated. It is concluded that new scales specifically designed to assess negative symptoms in CHR youth are needed to accurately chart mental illness trajectories and determine when, where, and how to intervene. Recent efforts to develop next-generation measures designed specifically for CHR youth to meet this urgent need in the field are discussed. These new approaches offer significant progress for addressing issues inherent to earlier scales.

Social reward processing: A biomarker for predicting psychosis risk?

The desire to obtain social rewards (e.g. positive feedback) features prominently in our lives and relationships, and is relevant to understanding psychopathology - where behavior is often impaired. Investigating social rewards within the psychosis-spectrum offers an especially useful opportunity, given the high rates of impaired social functioning and social isolation. The goal of this study was to investigate hedonic experience associated with social reward processing as a potential biomarker for psychosis risk. This study used a task-based functional magnetic resonance imaging (fMRI) paradigm in adolescents at clinical high-risk for the development of psychosis (CHR, n = 19) and healthy unaffected peers (healthy controls - HC, n = 20). Regional activation and connectivity of the ventromedial prefrontal cortex and ventral striatum were examined in response to receiving positive social feedback relative to an ambiguous feedback condition. Expectations of impaired hedonic processes in CHR youth were generally not supported, as there were no group differences in neural response or task-based connectivity. Although interesting relationships were found linking neural reward response and connectivity with social, anticipatory, and consummatory anhedonia in the CHR group, results are difficult to interpret in light of task limitations. We discuss potential implications for future study designs that seek to investigate social reward processing as a biomarker for psychosis risk.

Are Negative Symptoms Merely the "Real World" Consequences of Deficits in Social Cognition?

Many investigations have demonstrated that negative symptoms and social cognitive deficits in schizophrenia play a large role in determining functional outcomes and ultimately long-term prognosis. Given this, there is increasing interest in understanding the relationship between these two symptom domains, particularly since studies have consistently found moderate to large associations between them. This shared variance raises a key question: to what degree do these two categories of symptoms arise from overlapping or identical changes in brain function? In other words, do some or all negative symptoms represent merely the downstream effects of social cognition deficits on daily functioning? In this commentary, the evidence for and against this possibility, limitations of currently validated empirical measurements of these symptoms, and directions for further investigation of this hypothesis are discussed. Understanding the shared and distinct mechanisms of these disabling deficits will have important implications for the design of novel, personalized treatments for psychotic illness.