Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach.

Background: Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology. Methods: Participants included 49 CHR individuals and 42 healthy controls who completed a semi-structured narrative interview. Interview transcripts were analyzed using Linguistic Inquiry and Word Count (LIWC) to assess the emotional tone of the language (tone -the ratio of negative to positive language) and count positive/negative words used. Participants also completed clinical symptom assessments to determine CHR status and characterize symptoms (i.e., positive and negative symptom domains). Results: The CHR group had more negative emotional tone compared to healthy controls (t=2.676, p=.009), which related to more severe positive symptoms (r2=.323, p=.013). The percentages of positive and negative words did not differ between groups (p's>.05). Conclusions: Language analyses provided accessible, ecologically valid insight into affective dysfunction and psychosis risk symptoms. Natural language processing analyses unmasked differences in language for CHR that captured language tendencies that were more nuanced than the words that are chosen.

A Developmental Perspective on Early and Current Motor Abnormalities and Psychotic-Like Symptoms.

BACKGROUND AND HYPOTHESIS: Psychotic-like experiences (PLEs) are prevalent in the general population and, because they represent a lower end of the psychosis vulnerability spectrum, may be useful in informing mechanistic understanding. Although it is well-understood that motor signs characterize formal psychotic disorders, the developmental trajectory of these features and their relationships with PLEs are less well-understood. STUDY DESIGN: Data from 7559 adolescents and young adults (age 11-21) in the Philadelphia Neurodevelopmental Cohort were used to investigate whether early-life milestone-attainment delays relate to current adolescent sensorimotor functioning and positive and negative PLEs. Current sensorimotor functioning was assessed using the Computerized Finger Tapping task (assessing motor slowing) and Mouse Practice task (assessing sensorimotor planning). STUDY RESULTS: Early developmental abnormalities were related to current adolescent-aged motor slowing (t(7415.3) = -7.74, corrected-P < .001) and impaired sensorimotor planning (t(7502.5) = 5.57, corrected-P < .001). There was a significant interaction between developmental delays and current sensorimotor functioning on positive and negative PLEs (t = 1.67-4.51), such that individuals with early developmental delays had a stronger positive relationship between sensorimotor dysfunction and PLEs. Importantly, interaction models were significantly better at explaining current PLEs than those treating early and current sensorimotor dysfunction independently (χ2 = 4.89-20.34). CONCLUSIONS: These findings suggest a relationship between early developmental delays and current sensorimotor functioning in psychosis proneness and inform an understanding of heterotypic continuity as well as a neurodevelopmental perspective of motor circuits. Furthermore, results indicate that motor signs are a clear factor in the psychosis continuum, suggesting that they may represent a core feature of psychosis vulnerability.

Developmental changes in the endorsement of psychotic-like experiences from middle childhood through young adulthood.

BACKGROUND: Children tend to endorse psychotic-like experiences (PLEs) at higher rates than adults, although little is known about how specific symptom endorsement changes across the span of development. Here we take an observational approach to examine trends in PLE endorsement by age in two non-clinical samples: one of school-aged children and another of late adolescents and early adults. METHODS: Prodromal Questionnaire-Brief (child and adult versions) responses were investigated in individuals ages 9-13 (n = 11865) and 16-24 (n = 3209) from the Adolescent Brain and Cognitive Development Study (ABCD) and the Multisite Assessment of Psychosis-risk Study (MAP), respectively. Item-level endorsement and distressing item frequencies were examined by age throughout both cohorts. RESULTS: Unusual perceptual experiences were generally endorsed more heavily in childhood, while other PLEs were endorsed in adolescents and adults up to 4.8 times more frequently than in children. Additionally, certain experiences were endorsed by as many as 73 percent of the older sample. CONCLUSIONS: Considerations for the measurement of PLEs in childhood and adolescence are underscored. Findings from these two samples provide a window into the course of these PLEs and may serve as a scaffold for future research investigating normative versus risk-related experiences during development.

The impact of menarche on hippocampal mechanisms of severity of psychotic-like experiences in the ABCD study.

Accumulating evidence suggests that estrogens play an important modulatory role in the pathogenesis of psychosis. Estrogens come online within a dynamic developmental context of emerging psychopathology and neurodevelopment. As a result, estradiol (the primary form of estrogen) may influence psychosis lability directly or indirectly through its neurodevelopmental influence on estrogens-sensitive areas like the hippocampus. Understanding this influence may provide novel insight into mechanisms of psychosis lability. This study included baseline and year 2 timepoints from 4422 female participants from the Adolescent Brain Cognitive Development (ABCD) study (age 8-13), who varied in estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). Estradiol availability was related to psychotic-like experiences (PLE) severity both directly and as an interactive effect with hippocampal connectivity using menarche status (pre/post) in a multilevel model. PLE severity was highest in individuals with early menarche emphasizing the importance of the developmental timing. Although PLE severity decreased over time in the sample, it stayed clinically-relevant over 2 years. Lower hippocampal connectivity was related to elevated PLE severity. This effect was moderated by estradiol; before the availability of estradiol (pre-menarche), lower hippocampal connectivity significantly contributed to the PLE severity, but when estradiol was available (post-menarche) hippocampal dysconnectivity did not account for PLE severity. This moderation suggests that the estrodiol's influence on hippocampal plasticity also reduced the mechanistic role of the hippocampus on PLE severity. Further, the lack of a significant direct reduction of PLE severity post-menarche, may suggest an increased role for other interacting psychosis lability factors during this critical developmental period.

Physical and mental health in adolescence: novel insights from a transdiagnostic examination of FitBit data in the ABCD study.

Adolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10-13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of psychosis-like experiences (PLE), internalizing symptoms, and externalizing symptoms. Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t = -2.69) and internalizing (t = -6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.

A meta-analysis and systematic review of single vs. multimodal neuroimaging techniques in the classification of psychosis.

BACKGROUND: Psychotic disorders are characterized by structural and functional abnormalities in brain networks. Neuroimaging techniques map and characterize such abnormalities using unique features (e.g., structural integrity, coactivation). However, it is unclear if a specific method, or a combination of modalities, is particularly effective in identifying differences in brain networks of someone with a psychotic disorder. METHODS: A systematic meta-analysis evaluated machine learning classification of schizophrenia spectrum disorders in comparison to healthy control participants using various neuroimaging modalities (i.e., T1-weighted imaging (T1), diffusion tensor imaging (DTI), resting state functional connectivity (rs-FC), or some combination (multimodal)). Criteria for manuscript inclusion included whole-brain analyses and cross-validation to provide a complete picture regarding the predictive ability of large-scale brain systems in psychosis. For this meta-analysis, we searched Ovid MEDLINE, PubMed, PsychInfo, Google Scholar, and Web of Science published between inception and March 13th 2023. Prediction results were averaged for studies using the same dataset, but parallel analyses were run that included studies with pooled sample across many datasets. We assessed bias through funnel plot asymmetry. A bivariate regression model determined whether differences in imaging modality, demographics, and preprocessing methods moderated classification. Separate models were run for studies with internal prediction (via cross-validation) and external prediction. RESULTS: 93 studies were identified for quantitative review (30 T1, 9 DTI, 40 rs-FC, and 14 multimodal). As a whole, all modalities reliably differentiated those with schizophrenia spectrum disorders from controls (OR = 2.64 (95%CI = 2.33 to 2.95)). However, classification was relatively similar across modalities: no differences were seen across modalities in the classification of independent internal data, and a small advantage was seen for rs-FC studies relative to T1 studies in classification in external datasets. We found large amounts of heterogeneity across results resulting in significant signs of bias in funnel plots and Egger's tests. Results remained similar, however, when studies were restricted to those with less heterogeneity, with continued small advantages for rs-FC relative to structural measures. Notably, in all cases, no significant differences were seen between multimodal and unimodal approaches, with rs-FC and unimodal studies reporting largely overlapping classification performance. Differences in demographics and analysis or denoising were not associated with changes in classification scores. CONCLUSIONS: The results of this study suggest that neuroimaging approaches have promise in the classification of psychosis. Interestingly, at present most modalities perform similarly in the classification of psychosis, with slight advantages for rs-FC relative to structural modalities in some specific cases. Notably, results differed substantially across studies, with suggestions of biased effect sizes, particularly highlighting the need for more studies using external prediction and large sample sizes. Adopting more rigorous and systematized standards will add significant value toward understanding and treating this critical population.

Neurodevelopmental vulnerability to psychosis: developmentally-based methods enable detection of early life inhibitory control deficits that predict psychotic-like experiences at the transition to adolescence.

BACKGROUND: Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention. METHODS: Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3-5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; 'tween'; ages 9-12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8-11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control. RESULTS: Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F(1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4-9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F(2,202) = 5.618, p = 0.004, and externalizing symptoms, F(2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F(1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms. CONCLUSIONS: Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention.

Motor precision deficits in clinical high risk for psychosis.

Motor deficits appear prior to psychosis onset, provide insight into vulnerability as well as mechanisms that give rise to emerging illness, and are predictive of conversion. However, to date, the extant literature has often targeted a complex abnormality (e.g., gesture dysfunction, dyskinesia), or a single fundamental domain (e.g., accuracy) but rarely provided critical information about several of the individual components that make up more complex behaviors (or deficits). This preliminary study applies a novel implicit motor task to assess domains of motor accuracy, speed, recognition, and precision in individuals at clinical high risk for psychosis (CHR-p). Sixty participants (29 CHR-p; 31 healthy volunteers) completed clinical symptom interviews and a novel Serial Interception Sequence Learning (SISL) task that assessed implicit motor sequence accuracy, speed, precision, and explicit sequence recognition. These metrics were examined in multilevel models that enabled the examination of overall effects and changes in motor domains over blocks of trials and by positive/negative symptom severity. Implicit motor sequence accuracy, speed, and explicit sequence recognition were not detected as impacted in CHR-p. When compared to healthy controls, individuals at CHR-p were less precise in motor responses both overall (d = 0.91) and particularly in early blocks which normalized over later blocks. Within the CHR-p group, these effects were related to positive symptom levels (t = - 2.22, p = 0.036), such that individuals with higher symptom levels did not improve in motor precision over time (r's = 0.01-0.05, p's > 0.54). CHR-p individuals showed preliminary evidence of motor precision deficits but no other motor domain deficits, particularly in early performance that normalized with practice.

Social network size in adolescents at clinical high risk for psychosis.

AIMS: Adolescents and young adults at clinical high risk (CHR) for psychosis report few close friends. Social support has been linked to conversion to psychosis and psychosis relapse in CHR individuals. Expanding earlier research on loneliness and friendships at a single timepoint, this study described composition and changes in social network and its association with clinical and cognitive symptoms among CHR adolescents. METHODS: Ninety five individuals (46 CHR individuals, 49 healthy volunteers) completed baseline and 1-year follow-up Social Network Index (SNI) evaluations and clinical interviews. Analyses first examined SNI size and composition across 10 categories (e.g., family, close friends, coworkers, classmates) between groups. Then, the relationship between SNI size and baseline social symptoms (i.e., paranoia, social anhedonia, social anxiety, social cognition), social function, and changes in symptoms and social networks over 1-year were examined within the CHR group. RESULTS: CHR individuals showed smaller social networks overall, driven by fewer friendships and family relationships. Social cognition and social anxiety significantly related to SNI size at baseline, but social anhedonia and paranoia did not. SNI size related to social function, but with a modest effect size (r's = .45 and .56). Surprisingly, an increase in positive symptom severity related to an increase in familial but a decrease in coworker social network size. CONCLUSIONS: The social support deficits in the CHR group were specific to relatives and friendships, with social anxiety and social cognition as implicated symptoms. Social relationships may serve as a promising early intervention target in individuals at CHR for psychosis.

Association between reward-related functional connectivity and tri-level mood and anxiety symptoms.

Depression and anxiety are associated with abnormalities in brain regions that process rewards including the medial orbitofrontal cortex (mOFC), the ventral striatum (VS), and the amygdala. However, there are inconsistencies in these findings. This may be due to past reliance on categorical diagnoses that, while valuable, provide less precision than may be required to understand subtle neural changes associated with symptoms of depression and anxiety. In contrast, the tri-level model defines symptom dimensions that are common (General Distress) or relatively specific (Anhedonia-Apprehension, Fears) to depression and anxiety related disorders, which provide increased precision. In the current study, eligibility was assessed by quasi-orthogonal screening questionnaires measuring reward and threat sensitivity (Behavioral Activation Scale; Eysenck Personality Questionnaire-Neuroticism). These participants were assessed on tri-level symptom severity and completed the Monetary Incentive Delay task during fMRI scanning. VS-mOFC and VS-amygdala connectivity were estimated during reward anticipation and reward outcome. Heightened General Distress was associated with lower VS-mOFC connectivity during reward anticipation (b = -0.064, p = 0.021) and reward outcome (b = -0.102, p = 0.014). Heightened Anhedonia-Apprehension was associated with greater VS-amygdala connectivity during reward anticipation (b = 0.065, p = 0.004). The present work has important implications for understanding the coupling between the mOFC and vS and the amygdala and the vS during reward processing in the pathophysiology of mood and anxiety symptoms and for developing targeted behavioral, pharmacological, and neuromodulatory interventions to help manage these symptoms.

Hippocampal subfields, daily stressors, and resting cortisol in individuals at clinical high-risk for psychosis.

INTRODUCTION: The hippocampus, comprised of functionally distinct subfields, both regulates stress and is affected by it during psychosis pathogenesis. Hippocampal abnormalities are evident across psychosis spectrum and are associated with aberrant cortisol levels and greater environmental stressors exposure. These associations, particularly at the subfield-level, are poorly understood in individuals at clinical high-risk (CHR) for psychosis. This represents a significant literature gap given this critical pathogenetic period is characterized by an interplay between environmental stressors and biological susceptibility. METHODS: A total of 121 participants including 51 CHR (mean age=18.61) and 70 healthy controls (HC; mean age=18.3) were enrolled in the study. Participants completed a structural scan, salivary cortisol assays, and a self-report measure assessing distress from daily stressors exposure (DSI). Hippocampal subfield segmentation was conducted using Freesurfer. RESULTS: Smaller hippocampal subfields were associated with greater stress levels. Greater DSI was associated with lower volumes in CA1 (r = -0.38) and CA2/3 (r = -0.29), but not in CA4/DG (r = -0.28), presubiculum (r = -0.09), or subiculum (r = -0.17). Higher resting cortisol was associated with lower volumes in presubiculum (r = -0.4) but not subiculum (r = -0.22), CA1 (r = 0.08), CA2/3 (r = 0.1), or CA4/DG (r = -0.005). Regressions indicated effects for CA1 and DSI (ß = 0.57, p = .03) and presubiculum and cortisol (ß = 0.61, p = .02) are specific to CHR participants relative to HCs. CONCLUSIONS: The findings provided insights into links between stress and brain vulnerability during psychosis-risk period. Regional differences highlighted potentially different mechanisms by which stress impacts specific subfields. Presubiculum may be more susceptible to the impact of early stress on HPA-axis and cornu amonis to acute stressors.

Cerebellar correlates of social dysfunction among individuals at clinical high risk for psychosis.

Introduction: Social deficits are a significant feature among both individuals with psychosis and those at clinical high-risk (CHR) for developing psychosis. Critically, the psychosis risk syndrome emerges in adolescence and young adulthood, when social skill development is being fine-tuned. Yet, the underlying pathophysiology of social deficits in individuals at CHR for psychosis remains unclear. Literature suggests the cerebellum plays a critical role in social functioning. Cerebellar dysfunction in psychosis and CHR individuals is well-established, yet limited research has examined links between the cerebellum and social functioning deficits in this critical population. Method: In the current study, 68 individuals at CHR for developing psychosis and 66 healthy controls (HCs) completed social processing measures (examining social interaction, social cognition, and global social functioning) and resting-state MRI scans. Seed-to-voxel resting-state connectivity analyses were employed to examine the relationship between social deficits and lobular cerebellar network connectivity. Results: Analyses indicated that within the CHR group, each social domain variable was linked to reduced connectivity between social cerebellar subregions (e.g., Crus II, lobules VIIIa and VIIIb) and cortical regions (e.g., frontal pole and frontal gyrus), but a control cerebellar subregion (e.g., lobule X) and was unrelated to these social variables. Discussion: These results indicate an association between several cerebellar lobules and specific deficits in social processing. The cerebellum, therefore, may be particularly salient to the social domain and future research is need to examine the role of the cerebellum in psychosis.

The Interplay between Reward-Relevant Life Events and Trait Reward Sensitivity in Neural Responses to Reward Cues.

The reward hypersensitivity model posits that trait reward hypersensitivity should elicit hyper/hypo approach motivation following exposure to recent life events that activate (goal-striving and goal-attainment) or deactivate (goal-failure) the reward system, respectively. To test these hypotheses, eighty-seven young adults with high (HRew) versus moderate (MRew) trait reward sensitivity reported frequency of life events via the Life Event Interview. Brain activation was assessed during the fMRI Monetary Incentive Delay task. Greater exposure to goal-striving events was associated with higher nucleus accumbens (NAc) reward anticipation among HRew participants and lower orbitofrontal cortex (OFC) reward anticipation among MRew participants. Greater exposure to goal-failure events was associated with higher NAc and OFC reward anticipation only among HRew participants. This study demonstrated different neural reward anticipation (but not outcome) following reward-relevant events for HRew versus MRew individuals. Trait reward sensitivity and reward-relevant life events may jointly modulate reward-related brain function, with implications for understanding psychopathology.

Risk for bipolar spectrum disorders associated with positive urgency and orbitofrontal cortical grey matter volume.

Bipolar spectrum disorders (BSDs) are associated with reward hypersensitivity, impulsivity, and structural abnormalities within the brain's reward system. Using a behavioral high-risk study design based on reward sensitivity, this paper had two primary objectives: 1) investigate whether elevated positive urgency, the tendency to act rashly when experiencing extreme positive affect, is a risk for or correlate of BSDs, and 2) examine the nature of the relationship between positive urgency and grey matter volume in fronto-striatal reward regions, among individuals at differential risk for BSD. Young adults (ages 18-28) screened to be moderately reward sensitive (MReward; N = 42), highly reward sensitive (HReward; N = 48), or highly reward sensitive with a lifetime BSD (HReward + BSD; N = 32) completed a structural MRI scan and the positive urgency subscale of the UPPS-P scale. Positive urgency scores varied with BSD risk (MReward < HReward < HReward + BSD; ps≤0.05), and positive urgency interacted with BSD risk group in predicting lateral OFC volume (p <.001). Specifically, the MReward group showed a negative relationship between positive urgency and lateral OFC volume. By contrast, there was no relationship between positive urgency and lateral OFC grey matter volume among the HReward and HReward + BSD groups. The results suggest that heightened trait positive urgency is a pre-existing vulnerability for BSD that worsens with illness onset, and there is a distinct relationship between positive urgency and lateral OFC volume among individuals at high versus low risk for BSD. These findings have implications for understanding the expression and development of impulsivity in BSDs.

Evaluating the Social Functioning Scale modified for use in individuals at clinical high-risk for psychosis.

BACKGROUND: Social functioning deficits occur prior to the onset of psychosis and predict conversion to psychosis in clinical high-risk (CHR) populations. The Social Functioning Scale (SFS), a self-report measure of social functioning, is widely used in adults with psychosis but has not been tailored to CHR individuals. CHR syndromes overlap with the adolescent/young-adult developmental period, a time with unique social demands and contexts. The current study evaluates a modified version of the SFS in CHR individuals. METHODS: Two independent samples of CHR participants (n = 84 and n = 45) and non-CHR participants (n = 312 and n = 42) completed the SFS and a psychosis-risk interview. Resulting factors were compared across diagnostic categories (CHR, Major Depressive Disorder, Generalized Anxiety Disorder) and community controls (CC) who were not excluded for any psychopathology except psychosis, depression, and anxiety. CHR participants completed scales of negative symptoms, global social and role functioning, cognition, and finger tapping as measures of convergent and divergent validity. RESULTS: Exploratory factor analysis identified three SFS factors (RMSEA = 0.05) which demonstrated reliability in a confirmatory analysis in an independent sample: Recreation (α = 0.82), Nightlife (α = 0.85), and Interpersonal (α = 0.69). Factors and their composite score demonstrated increased social deficits in CHR compared to CC and depression groups and showed expected convergent (r's = 0.30-0.54) and divergent (r's = -0.004-0.26) validity with appropriate measures. CONCLUSIONS: These findings suggest that there are reliable, valid, and developmentally relevant categories of social behavior within the SFS that differentiate between CHR and MDD or CC individuals. Recommendations for future work with CHR populations are included.

Interactions between the cortical midline structures and sensorimotor network track maladaptive self-beliefs in clinical high risk for psychosis.

Individuals at clinical high risk for psychosis (CHR) report a maladaptive self-concept-with more negative and less positive self-beliefs-linked to clinical symptoms and functional impairment. Alterations have also been reported in brain networks associated with intrinsic (cortical midline structures, CMS) and extrinsic (sensorimotor network, SMN) self-processing. Theoretical accounts of multiple levels of self-experience in schizophrenia suggest that interactions between these networks would be relevant for self-beliefs. This study tested whether self-beliefs related to resting-state functional connectivity within and between the CMS and SMN. Participants were 56 individuals meeting CHR criteria and 59 matched healthy community participants (HC). Pearson correlations examined potential mediators and outcomes. The CHR group reported more negative and less positive self-beliefs. Greater resting-state functional connectivity between the posterior CMS (posterior cingulate cortex) and the SMN was associated with less positive self-beliefs in CHR, but more positive self-beliefs in HC. Attenuated negative symptoms and poorer social functioning were associated with CMS-SMN connectivity (trend level after FDR-correction) and self-beliefs. Reduced connectivity between the left and right PCC was associated with lower positive self-beliefs in CHR, although this effect was specific to very low levels of positive self-beliefs. Left-right PCC connectivity did not correlate with outcomes. Dynamic interactions between intrinsic and extrinsic self-processing supported positive self-beliefs in typically developing youth while undermining positive self-beliefs in CHR youth. Implications are discussed for basic self-fragmentation, narrative self-related metacognition, and global belief updating. Interventions for self-processing may be beneficial in the CHR syndrome.

Exercise Intervention in Individuals at Clinical High Risk for Psychosis: Benefits to Fitness, Symptoms, Hippocampal Volumes, and Functional Connectivity.

BACKGROUND AND HYPOTHESIS: Individuals at clinical high risk for psychosis (CHR-p) are less fit than nonclinical peers and show hippocampal abnormalities that relate to clinical symptoms. Exercise generates hippocampal neurogenesis that may ameliorate these hippocampal abnormalities and related cognitive/clinical symptoms. This study examines the impact of exercise on deficits in fitness, cognitive deficits, attenuated psychotic symptoms, hippocampal volumes, and hippocampal connectivity in individuals at CHR-p. STUDY DESIGN: In a randomized controlled trial, 32 individuals at CHR-p participated in either an exercise (n = 17) or waitlist (no exercise) (n = 15) condition. All participants were sedentary at use and absent of current antipsychotic medication, psychosis diagnoses, or a substance use disorder. The participants completed a series of fitness, cognitive tasks, clinical assessments, and an MRI session preintervention and postintervention. The exercise intervention included a high-intensity interval exercise (80% of VO2max) with 1-minute high-intensity intervals (95% of VO2max) every 10 minutes) protocol twice a week over 3 months. STUDY RESULTS: The exercise intervention was well tolerated (83.78% retention; 81.25% completion). The exercising CHR-p group showed that improved fitness (pre/post-d = 0.53), increased in cognitive performance (pre/post-d = 0.49), decrease in positive symptoms (pre/post-d = 1.12) compared with the waitlist group. Exercising individuals showed stable hippocampal volumes; waitlist CHR-p individuals showed 3.57% decreased hippocampal subfield volume. Exercising individuals showed that increased exercise-related hippocampal connectivity compared to the waitlist individuals. CONCLUSIONS: The exercise intervention had excellent adherence, and there were clear signs of mechanism engagement. Taken together, evidence suggests that high-intensity exercise can be a beneficial therapeutic tool in the psychosis risk period.

Developmental patterning of irritability enhances prediction of psychopathology in preadolescence: Improving RDoC with developmental science.

The transdiagnostic importance of irritability in psychopathology has been demonstrated. However, the contribution of developmentally unfolding irritability patterns to specific clinical and neural outcomes remains an important and unanswered question. To address this gap in the literature, irritability patterns of 110 youth from a large, diverse cohort were assessed at preschool age and again at early school age (∼2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum. At preadolescence (∼6 years later), clinical outcomes (internalizing/externalizing symptoms) derived from a semistructured clinical interview and neural outcomes (characterized as gray-matter-volume abnormalities) were assessed. For clinical outcomes, preschool-age irritability alone was a transdiagnostic predictor of internalizing and externalizing symptoms at preadolescence. However, in a model including both preschool and early school age, irritability provided greater specificity, suggesting that higher irritability at early school age related to elevated preadolescent externalizing but not internalizing symptoms. In terms of neural outcomes, elevated preschool irritability did not predict preadolescent gray-matter-volume abnormality; however, irritability at early school age demonstrated an interactive effect among regions, with reduced volume in preadolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). These complex patterns highlight the contribution of a developmentally informed approach, the National Institute of Mental Health's Research Domain Criteria (RDoC) approach, to yield transdiagnostic phenotypes and multiple units of analysis. Capturing these individual differences and developmental heterogeneity can provide critical insight into the unfolding of mechanisms underlying emerging psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Depression and Psychosis Risk Shared Vulnerability for Motor Signs Across Development, Symptom Dimensions, and Familial Risk.

BACKGROUND: Motor abnormalities are strong transdiagnostic indicators of psychopathology risk that reflect emerging neural network abnormalities. Indeed, motor signs, such as motor slowing and agitation, are widely recognized as core features of both psychosis and depression. However, it is unclear whether these reflect shared or distinct etiology. METHODS: A sample of 11 878 adolescents completed self-reported clinical measures of rated psychotic-like experiences (PLEs) and depression. Familial risk for psychopathology and the presence of motor signs were drawn from parental reports, including developmental motor delays (eg, sitting, walking), and adolescent motor signs (eg, dyscoordination, psychomotor retardation, and psychomotor agitation). Finally, motor network connectivity in theoretically relevant networks (cortico-striatal, cortico-thalamic, and cortico-cerebellar) were related to symptoms and familial risk for psychopathology. RESULTS: Developmental motor delays related to increased PLEs, increased depression symptoms, and greater familial risk. Familial risk for both PLEs and depression showed higher rates of developmental motor delays than all other groups. Adolescent motor signs, however, showed unique patterns of relationships to symptoms and familial risk such that dyscoordination reflected risk for PLEs, both psychomotor agitation and retardation reflected depression risk, and psychomotor agitation reflected transdiagnostic risk. Cortico-striatal connectivity was related to depression and PLEs, but cortico-cerebellar connectivity was linked to PLEs only. CONCLUSIONS: Motor signs may be a transdiagnostic marker of vulnerability for psychopathology. Early developmental motor delays could belie pluripotent, familial risk features. Unique items, eg, dyscoordination specifically related to PLEs, possibly reflecting processes inherent in distinct emerging forms of psychopathology.

Anxiety symptoms, rule learning, and cognitive flexibility in non-clinical psychosis.

Individuals with psychotic-like experiences (PLEs) represent a critical group for improving the understanding of vulnerability factors across the psychosis continuum. A growing body of literature has identified functional deficits associated with PLEs. However, it is unclear if such deficits purely reveal the underlying psychosis vulnerability or if they are also linked with comorbid anxiety symptoms. Although anxiety disorders are often associated with impairments in psychosis-risk, symptoms of anxiety may facilitate executive functioning in certain psychosis groups. The Community Assessment of Psychic Experiences was completed to assess psychosis-like symptoms in a total of 57 individuals, and its median score was used to categorize PLE groups (high-PLE = 24, low-PLE = 33). Anxiety symptoms were measured via the Beck Anxiety Inventory, and cognitive flexibility was measured by the Penn Conditional Exclusion Test. The high-PLE group endorsed more anxiety symptoms, demonstrated poorer accuracy and efficiency on the cognitive task, and made more perseverative errors compared to the low-PLE group. Within the high-PLE group, higher levels of anxiety symptoms were associated with better performance and less perseverative errors compared to individuals with lower levels of anxiety symptoms. Conversely, greater anxiety symptoms were associated with poorer performance in the low-PLE group. Taken together, these findings provide a preliminary support for a potential psychosis vulnerability × anxiety symptom interaction. Given the interest in the psychosis continuum and potential treatment implications, the present findings warrant replication efforts.