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Evidence shows that reports of psychopathology symptoms by youth and their caregiver informants differ. To quantify youth-caregiver discrepancies in psychopathology symptoms and factors associated with such discrepancies, we investigated differences in how youth and their caregivers rated psychopathology symptoms. The sample (N = 5094) was extracted from the Philadelphia Neurodevelopmental Cohort, a community-based sample of youth and included participants ages 11-17 years old with both youth and caregiver reported symptom scores. Across psychopathology symptoms, youth-caregiver concordance was poor to fair (Cohens kappa for symptom items ranged between 0.03–0.41). Psychosis symptoms had the lowest concordance—Cohen's kappa ranged from 0.03 to 0.17 across psychosis symptoms. Discrepancies between youth and caregiver symptom reports were greater than average for Black youth and for youth of low socioeconomic status; discrepancies were also higher than average in youth with any psychiatric disorder when compared to typically developing youth. Network analysis of difference scores obtained by subtracting youth symptom scores from caregiver reported symptom scores showed that network connectivity (i.e., correlated difference scores) was sparsest for psychosis spectrum compared to other psychiatric disorders. Using a large sample, we show that youth and their caregiver informants tend to report psychopathology symptoms differently. Youth-caregiver discrepancies were the most pronounced for Black youth and youth of low socio-economic status. Race and socioeconomic status contribute to significant differences in how youth and their caregivers report such symptoms and are important factors that should be accounted for to facilitate accurate mental health symptom assessment and evaluation. [ABSTRACT FROM AUTHOR]

Background: Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of 'risk calculators' for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples. Methods: We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting 'psychosis risk' enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines. Results: Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70. Conclusions: Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS. [ABSTRACT FROM AUTHOR]

Background: Traumatic stressful events (TSEs) are among the most studied risk factors for subsequent schizotypal symptoms. However, specificity and aggregate effects of trauma exposure on schizotypal symptoms remain unclear. This study investigates these relationships among a community-based sample of US adolescents.Material and Methods: A sub-sample of 426 adolescents (51.6% female) from the Philadelphia Neurodevelopmental Cohort study were selected for longitudinal follow-up based on presence (n = 209) or absence (n = 217) of psychosis spectrum symptoms (PSS). At baseline, they completed assessments of demographic, TSEs, other psychopathology (e.g., PSS, anxiety, depression, and behavioral disorder) and family history of psychopathology. Schizotypal symptom dimensions (cognitive-perceptual, interpersonal and disorganized) were evaluated approximately two years later.Results: More than half of adolescents experienced at least one type of TSE. Adolescents with assaultive trauma reported about 1.5 times as many symptoms on all three schizotypal symptom dimensions, compared to adolescents with non-assaultive TSE, adjusting for demographic and family history variables. No statistical significance was found after further adjusting for other baseline psychopathology (p > 0.05). There was a significant aggregate effect of TSEs on cognitive-perceptual symptoms with small effect size (p < 0.001, Cohen's f2 = 0.034).Conclusions: We found evidence of an association between aggregate TSEs and cognitive-perceptual symptoms, but trauma type was not associated with schizotypal symptom dimensions when controlling for potential confounders. Our findings highlight the importance of considering aggregate TSE effects and potential confounds when examining associations between TSEs and schizotypy. Trauma and psychosis spectrum screening may be important in the effort to provide trauma-informed care. [ABSTRACT FROM AUTHOR]

Prevailing models of psychosis risk incorporate positive subthreshold symptoms as defining features of risk or transition to psychotic disorders. Despite this, relatively few studies have focused on characterizing longitudinal symptom features, such as prevalence, concordance and structure, which may aid in refining methods and enhancing classification and prediction efforts. The present study aimed to fill these gaps using longitudinal 24-month follow-up data from the well-characterized NAPLS-2 multi-site investigation of youth at clinical high risk (CHR) who had (n = 86) and had not (n = 268) transitioned to a threshold psychotic disorder since baseline. At baseline, among sub-delusional ideas, unusual thought content and suspicious/persecutory thinking were very common in CHR youth, and were highly concordant. Perceptual abnormalities (P4) were also common across youth regardless of symptom course and eventual transition to psychosis. Grandiose ideas were rare. Exploratory factor analysis extracted two constituent factors at multiple follow-up intervals, but there was marked instability in the structure over 24 months, and clear indicators for a single positive symptom factor. Together these findings support suggestions to combine sub-delusional symptoms into a single symptom category for classification purposes, in efforts to reduce clinical heterogeneity and ease measurement burden. [ABSTRACT FROM AUTHOR]

The categorical approach to defining schizophrenia spectrum disorders requires meeting established criteria. To advance early identification and intervention in young people, the field has progressed to studying help-seeking individuals who are at clinical high risk based on subthreshold psychosis spectrum symptoms, and criteria have been articulated for qualifying individuals as at risk. A broader dimensional examination of psychosis has been applied to population-based studies on non–help seekers. This review highlights the ascertainment and assessment approaches to such population-based studies. Most studies are cross-sectional and rely on questionnaires with limited overlap of tools. However, several consistent findings emerge on symptoms, neurocognitive deficits, and neuroimaging parameters and other biomarkers associated with emergence and persistence of psychotic features. The findings are consistent with the literature on abnormalities associated with schizophrenia, including the presence of neurocognitive deficits; abnormalities in brain structure, function, and connectivity that are related to distress; impairment; and functional outcome. These findings support the validity of studying psychosis experiences during development in a way that can chart the emergence of psychosis in the context of general psychopathology. Such studies are necessary for establishing developmental trajectories that characterize this emergence and for identifying risk and resilience biomarkers moderating or modulating the full range of schizophrenia-related manifestations. More community-based studies are needed, with better standardization and harmonization of measures and incorporating longitudinal follow-up, to establish mechanistic links between cellular–molecular aberrations and specific manifestations of psychosis as envisioned by the precision medicine agenda. [ABSTRACT FROM AUTHOR]

A substantial body of work supports the existence of a general psychopathology factor ("p"). Psychometrically, this is important because it implies that there is a psychological phenomenon (overall psychopathology) that can be measured and potentially used in clinical research or treatment. The present study aimed to construct, calibrate, and begin to validate a computerized adaptive (CAT) screener for "p". In a large community sample (N = 4544; age 11–21), we modeled 114 clinical items using a bifactor multidimensional item response theory (MIRT) model and constructed a fully functional (and public) CAT for assessing "p" called the Overall mental illness (OMI) screener. In a random, non-overlapping sample (N = 1019) with extended phenotyping (neuroimaging) from the same community cohort, adaptive versions of the OMI screener (10-, 20-, and 40-item) were simulated and compared to the full 114-item test in their ability to predict demographic characteristics, common mental disorders, and brain parameters. The OMI screener performed almost as well as the full test, despite being only a small fraction of the length. For prediction of 13 mental disorders, the mid-length (20-item) adaptive version showed mean area under the receiver operating characteristic curve of 0.76, compared to 0.79 for the full version. For prediction of brain parameters, mean absolute standardized relationship was 0.06 for the 20-item adaptive version, compared to 0.07 for the full form. This brief, public tool may facilitate the rapid and accurate measurement of overall psychopathology in large-scale studies and in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. Methods: The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered. Results: Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β =.378); psychosis spectrum (β =.360); externalizing behaviors (β =.311); and fear (β =.256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition. Conclusions: Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression. [ABSTRACT FROM AUTHOR]

One of the most widely used measures of psychosis-related symptoms and characteristics is the 74-item Schizotypal Personality Questionnaire (SPQ). Using multidimensional Item Response Theory (bifactor 2-parameter model), we calibrated SPQ items in a sample of 375 youths aged 9–24 years and constructed a fully functional computerized adaptive form of the SPQ on an open-source platform for public use. To assess validity, we used the above parameters to simulate CAT sessions in a separate validation sample ( N = 100) using three test-length-based stopping rules: 8 items, 16 items, and 32 items. Those scores were then compared to full-form and SPQ-Brief scores on their abilities to predict psychosis or clinical risk status. Areas under the receiver operating characteristic curves indicated mediocre predictive ability, but did not differ among any of the forms, even when only eight adaptive items were administered. The Youden index for the 16-item adaptive version was higher than that for the 22-item SPQ-Brief. Classification accuracy for the full SPQ was 73% compared to 66% for the both the SPQ-Brief and adaptive versions (average of three stopping rules). The SPQ-CAT shows promise as a much shorter but valid assessment of schizotypy which can save time with minimal loss of information. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence implicates advanced paternal age at offspring birth in neuropsychiatric disorders. Advanced maternal age has also been associated with schizophrenia and other neurodevelopmental disorders, whereas younger maternal age has been linked with behavioral disorders. Few studies have considered the specificity of the associations with respect to comorbidity. In addition, most prior studies have been conducted in clinical samples or registries that may reflect more severe forms of psychopathology. The aim of this research is to examine the independent and joint associations of maternal and paternal age with specific subtypes of psychopathology in offspring in a pediatric sample of adolescents with emergent psychiatric syndromes.Method: A total of 8,725 youths (aged 8-21 years) from the Philadelphia Neurodevelopmental Cohort were included in the analyses. Logistic regression models with parental age predicting offspring psychopathology were adjusted for sociodemographic factors and comorbid disorders.Results: We found that younger parental ages were generally associated with increased rates of offspring psychopathology. After controlling for sociodemographic characteristics and comorbidity, both younger maternal and paternal ages were associated with behavior syndromes and psychosis in youth, whereas advanced paternal age was associated with pervasive developmental disorders/autism spectrum disorder (PDD/ASD).Conclusion: These findings suggest that both younger and older parental age at birth are associated with specific forms of psychopathology in offspring. The persistence of the influence of parental age after control for demographic factors and an index of social environment suggests that additional explanations for these findings should be examined in future studies. [ABSTRACT FROM AUTHOR]

Schizophrenia and other psychosis spectrum disorders do not develop de novo but emerge from prodromal stages that are named and operationalized differently depending on the research group or consortium and its theoretical orientation. As a result, a complex lexicon now exists for characterizing individuals' risk of subclinical symptoms converting to psychosis. Researchers aim to develop instruments and methods to identify people at risk of psychosis, better understand their risks, and offer preventative treatments to arrest conversion to psychosis; ethical and policy questions loom large with each of these projects. In this paper, we canvass the lexical complexities of the at-risk status for psychosis and then consider ethical and policy challenges that researchers and clinicians face in disclosing, preventing, and treating psychosis risk. [ABSTRACT FROM AUTHOR]

Background: An integrative multidisciplinary approach is required to elucidate the multiple factors that shape neurodevelopmental trajectories of mental disorders. The Philadelphia Neurodevelopmental Cohort (PNC), funded by the National Institute of Mental Health Grand Opportunity (GO) mechanism of the American Recovery and Reinvestment Act, was designed to characterize clinical and neurobehavioral phenotypes of genotyped youths. Data generated, which are recently available through the NIMH Database of Genotypes and Phenotypes (dbGaP), have garnered considerable interest. We provide an overview of PNC recruitment and clinical assessment methods to allow informed use and interpretation of the PNC resource by the scientific community. We also evaluate the structure of the assessment tools and their criterion validity. Methods: Participants were recruited from a large pool of youths (n = 13,958) previously identified and genotyped at The Children's Hospital of Philadelphia. A comprehensive computerized tool for structured evaluation of psychopathology domains (GOASSESS) was constructed. We administered GOASSESS to all participants and used factor analysis to evaluate its structure. Results: A total of 9,498 youths (aged 8-21; mean age = 14.2; European American = 55.8%; African American = 32.9%; Other = 11.4%) were enrolled. Factor analysis revealed a strong general psychopathology factor, and specific 'anxious-misery', 'fear', and 'behavior' factors. The 'behavior' factor had a small negative correlation (0.21) with overall accuracy of neurocognitive performance, particularly in tests of executive and complex reasoning. Being female had a high association with the 'anxious-misery' and low association with the 'behavior' factors. The psychosis spectrum was also best characterized by a general factor and three specific factors: ideas about 'special abilities/ persecution,' 'unusual thoughts/perceptions', and 'negative/disorganized' symptoms. Conclusions: The PNC assessment mechanism yielded psychopathology data with strong factorial validity in a large diverse community cohort of genotyped youths. Factor scores should be useful for dimensional integration with other modalities (neuroimaging, genomics). Thus, PNC public domain resources can advance understanding of complex interrelationships among genes, cognition, brain, and behavior involved in neurodevelopment of common mental disorders. Keywords: Community cohort, children, adolescents, young adults, psychopathology, mood, anxiety, behavior, psychosis, comorbidity, structure, genomics, neuroimaging, neurocognition, public domain. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine patterns of associations between a broad range of mental and physical conditions by using a large, systematically obtained pediatric registry. METHODS: The sample included 9014 youth ages 8 to 21 years (4349 males and 4665 females; 3585 aged,13 years, 3678 aged 13 to 18 years, and 1751 aged 19 to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through pediatric clinics at the Children's Hospital of Philadelphia health care network by the Center for Applied Genomics. Measures were as follows: physical condition based on electronic medical records and interview data on 42 physical conditions of 14 organ systems/specialties and mental disorders based on an abbreviated version of the structured Kiddie-Schedule for Affective Disorders and Schizophrenia psychiatric diagnostic interview. RESULTS: There was a direct association between the severity of the physical condition and most classes of mental disorders, as well as with functional impairment. Models adjusted for sociodemographic correlates, other physical and mental disorders, and false discovery and revealed broad patterns of associations between neurodevelopmental disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.3-1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1; 95% CI: 2.7-3.6; P < .0001), and neurologic/central nervous system conditions (OR: 1.3; 95% CI: 1.1-1.9; P < .05) with mood disorders and attention-deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1-1.5; P < .001), and autoimmune/ inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1-1.8, P < .05). CONCLUSIONS: Findings show the strong overlap between physical and mental conditions and their impact on severity and functional impairment in youth. Specific patterns of comorbidity have important implications for etiology. Prospective tracking of cross-disorder morbidity will be important to establish more effective mechanisms for prevention and intervention. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Methods: Participants (n=1967; schizophrenia=369; first-degree relatives=1072; community comparison subjects=526) in the Consortium on the Genetics of Schizophrenia were administered the Penn Computerized Neurocognitive Battery. Results: Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in six of seven domains, proband scores predicted the performance of their unaffected siblings. Male, but not female, proband performance was predictive of their unaffected relatives’ (siblings and mothers) performance, most consistently in face memory and spatial processing. Conclusions: Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male proband performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families. [Copyright &y& Elsevier]

Objective: The objective of this study is to scrutinize whether psychopathology symptom networks differ between those with and without lifetime: treatment seeking, treatment and treatment of longer duration. Methods: We created non‐exclusive groups of subjects with versus without lifetime treatment seeking, treatment and treatment of mid‐long‐term duration. We estimated Ising models and carried out network comparison tests (NCTs) to compare (a) overall connectivity and (b) network structure. Furthermore, we examined node strength. We used propensity score matching (PSM) to minimize potential confounding by indication for service use. Results: Based on data from 9,172 participants, there were no statistically significant differences in overall connectivity and network structure in those with versus without lifetime: treatment seeking (p =.75 and p =.82, respectively), treatment (p =.63 and p =.49, respectively) and treatment of mid‐longterm duration (p =.15 and p =.62, respectively). Notably, comparing networks with versus without service use consistently revealed higher node strength in 'obsessions' and 'aggression' and lower node strength in 'elevated mood' in all networks with service use. Conclusions: Findings suggest that after adjusting for potential confounding by indication for service use, there was no indication of an association in overall connectivity or network structure for lifetime treatment seeking, treatment and treatment of longer duration. However, selected structurally important symptoms differed consistently in all three comparisons. Our findings highlight the potential of network analysis methods to examine treatment mechanisms and outcomes. Specifically, more granular network characteristics on the node level may complement and enrich traditional outcomes in clinical research. [ABSTRACT FROM AUTHOR]

Objective: Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. Method: Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. Results: The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/ flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. Conclusions: Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies. [ABSTRACT FROM AUTHOR]

Abstract: Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies. [Copyright &y& Elsevier]

Abstract: The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia. [Copyright &y& Elsevier]

Objective: Face recognition memory deficits in schizophrenia are attributed to frontotemporal dysfunction. Biological relatives of patients have similar deficits, suggesting genetic susceptibility. Because the impairment may reflect generalized object memory deficits, the authors evaluated both face and visual object recognition. Method: The Penn Face Memory Test and Visual Object Learning Test were given to 102 patients with schizophrenia, 60 of their biological relatives, and 135 healthy comparison subjects. Results: Significant immediate and delayed face recognition deficits were observed in patients and their relatives. Although patients were more impaired in visual object memory than comparison subjects, relatives were not. Conclusions: Face recognition deficits in patients with schizophrenia and their families are not secondary to generalized object memory deficits and may be an endophenotype reflecting frontotemporal impairment. [ABSTRACT FROM AUTHOR]

Schizophrenia patients and their relatives have been found to exhibit increased reflexive errors on the antisaccade task, suggesting the deficit reflects genetic susceptibility for schizophrenia. To evaluate the degree to which antisaccade error is elevated in schizophrenia relatives, we carried out a meta-analysis of the existing literature and a primary study examining whether the magnitude of reported differences between relative and nonpsychiatric comparison groups could be due to differences in participant inclusion criteria. Meta-analysis yielded a moderate to large effect size across studies comparing relatives and controls (Cohen''s d=0.61; Glass'' dg=0.87). Antisaccade performance in medically and psychiatrically healthy relatives (n=45), who were selected from a larger sample of relatives based on criteria applied to healthy controls, was significantly more impaired than in healthy control participants (d=0.81, dg=0.93). Moreover, excluded (n=71) and included relatives did not differ (d=0.14, dg=0.13). The results indicate that the antisaccade deficit is a robust phenomenon in unaffected schizophrenia relatives that is not due to differences in inclusion criteria between relatives and controls, and thus are consistent with a growing literature indicating that the antisaccade deficit will be a valuable endophenotype of schizophrenia. [Copyright &y& Elsevier]

Several forms of eye movement dysfunction (EMD) have been widely regarded as candidate endophenotypes of schizophrenia, ultimately capable of identifying individuals carrying schizophrenia susceptibility genes and elucidating the pathophysiology of schizophrenia. As an indication of their trait-like status, candidate endophenotypes optimally evidence stability over time. However, there have been few published reports of test–retest reliability of several forms of EMD in schizophrenia patients and their relatives. In the current investigation, schizophrenia patients and the first-degree biological relatives of schizophrenia patients (n=15) were administered by an eye movement battery including smooth pursuit, antisaccade and prosaccade tasks, and re-tested after an average of 1.82 years (range=14–24 months). Adequate test–retest reliabilities of smooth pursuit closed-loop gain (Pearson r=0.72), antisaccade error rate (r=0.73), saccade reaction time to correct antisaccade responses (r=0.73), and prosaccade hypometria (r=0.72) were observed. Lower reliabilities were obtained for smooth pursuit open-loop gain (r=0.52) and prosaccade reaction time (r=0.43). The results are supportive of the trait-like characteristics of particular forms of EMD in schizophrenia families and of the candidacy of EMD as an endophenotypic marker of schizophrenia. [Copyright &y& Elsevier]

Studies whether misclassification of blinks as saccades affect saccade rates when the presence of a blink is determined using only infrared oculography recordings of eye position. Methods for recording eye movements; Blink monitoring in patients with schizophrenia.

Examines the association of saccadic disinhibition with genetic liability in patients with acute and remitted schizophrenia. Use of antisaccade task performance as indicator of prefrontal integrity; Difficulty of schizophrenics in inhibiting unwanted saccades; Impact of medications on antisaccade deficits regardless of clinical state.

Background: Validated screening tools are needed to detect subtle cognitive impairment in individuals at-risk for developing psychosis. Here, the utility of the Mini-Mental Status Examination (MMSE) and Penn Computerized Neurocognitive Battery (CNB) were evaluated for detecting cognitive impairment in individuals with psychosis spectrum (PS) symptoms.Methods: Participants (n = 229; 54 % female) completed the MMSE and CNB at baseline and two-year follow-up. PS (n = 91) and typically developing (TD; n = 138) participants were enrolled at baseline based on the presence or absence of PS symptoms. After two years, 65 participants remained PS, 104 participants remained TD, 23 participants had Emergent (EP) subthreshold PS symptoms, and 37 participants were experiencing Other Psychopathology (OP).Results: Generally, those with PS had lower scores than TD on both the MMSE (p < 0.0001) and CNB (p < 0.0001). Additionally, OP participants performed lower on the MMSE than TD (p = 0.02). Receiver operating characteristic (ROC) analyses indicated similar area under the curve (AUCs) for the two instruments (0.67); the MMSE showed higher specificity (0.71 vs. 0.62), while the CNB showed higher sensitivity (0.66 vs 0.52). Use of the MMSE and CNB in combination provided the highest diagnostic classification.Conclusion: The MMSE and CNB can be used to screen for cognitive impairment in PS. The MMSE is better at ruling out PS-related cognitive impairment while the CNB is better at ruling in PS-related cognitive impairment. Overall, our results indicate that both tests are useful in screening for cognitive impairment, particularly in combination, in a PS population. [ABSTRACT FROM AUTHOR]

Hoarding behavior is prevalent in children and adolescents, yet clinicians do not routinely inquire about it and youth may not spontaneously report it due to stigma. It is unknown whether hoarding behavior, over and above obsessive-compulsive symptoms (OCS), is associated with major clinical factors in a general youth population. This observational study included N = 7054 youth who were not seeking help for mental health problems (ages 11–21, 54% female) and completed a structured interview that included evaluation of hoarding behavior and OCS, as a part of the Philadelphia Neurodevelopmental Cohort between November 2009 and December 2011. We employed regression models with hoarding behavior and OCS (any/none) as independent variables, and continuous (linear regression) or binary (logistic regression) mental health measures as dependent variables. All models covaried for age, sex, race, and socioeconomic status. A total of 374 participants endorsed HB (5.3%), most of which reported additional OCS (n = 317). When accounting for OCS presence, hoarding behavior was associated with greater dimensional psychopathology burden (i.e., higher P-factor) (β = 0.19, p <.001), and with poorer functioning (i.e., lower score on the child global assessment scale) (β = − 0.07, p <.001). The results were consistent when modeling psychopathology using binary variables. The results remained significant in sensitivity analyses accounting for count of endorsed OCS and excluding participants who met criteria for obsessive-compulsive disorder (n = 210). These results suggest that hoarding behavior among youth is associated with poorer mental health and functioning, independent of OCS. Brief hoarding-behavior assessments in clinical settings may prove useful given hoarding behavior's stigma and detrimental health associations. [ABSTRACT FROM AUTHOR]

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland. Using data collected from 2021 to 2023, we examined lifetime and recent smoking and vaping and compared smokers and vapers to nonusers on symptoms, functioning, and substance use. The sample included 445 participants aged 13–35 with recent psychosis onset. Assessments were collected by program staff. Overall, 28 % of participants engaged in either smoking or vaping within 30 days of the admission assessment. Smokers and vapers were disproportionately male, cannabis users, and had lower negative symptom severity than non-smokers. Vapers had higher role and social functioning. Both smoking and vaping were related to a longer time from psychosis onset to program enrollment. We compare these findings to previous studies and suggest steps for addressing smoking and vaping in this vulnerable population. [ABSTRACT FROM AUTHOR]

Coordinated Specialty Care (CSC) is an evidence-based model for early intervention of first episode psychosis (FEP). Monitoring fidelity to CSC models is essential for proper evaluation of program outcomes and quality improvement. To address variability across CSC programs and fidelity assessment-associated burden, an adapted fidelity scale was developed and implemented statewide in Pennsylvania. This report describes the design and preliminary performance of the adapted scale. The Pennsylvania FEP Fidelity Scale (PA-FEP-FS) assesses adherence to the CSC model by focusing on essential model components of other established fidelity scales, in tandem with program evaluation data. Initial data from fourteen PA-FEP sites from 2018 to 2021 were examined as preliminary validation. Assessment-associated burdens and costs were also estimated. PA-FEP-FS captured essential components of CSC models and proved feasible for implementation across varying program structures, while minimizing burden and cost. Programs utilized annual feedback as CSC benchmarks, evidenced by increased scores over time. PA-FEP-FS provides a model for adapting CSC fidelity scales to meet state- or local-level requirements while reducing assessment burdens and costs that may be associated with existing scales. [ABSTRACT FROM AUTHOR]

The two most used semi‐structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Structured Interview for Psychosis‐Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Developing harmonized psychometric criteria for defining CHR and associated outcomes would be beneficial for future research. This article describes the first step in this process by reporting on a NIMH workshop held in Washington DC, in February 2019 that was attended by experts in the field. The aim of this workshop was to examine the similarities and differences between the two measures and consider how the harmonization process could proceed. [ABSTRACT FROM AUTHOR]

The psychosis spectrum (PS) is associated with structural dysconnectivity concentrated in transmodal cortex. However, understanding of this pathophysiology has been limited by an overreliance on examining direct interregional connectivity. Using network control theory, we measured variation in both direct and indirect connectivity to a region to gain new insights into the pathophysiology of the PS. We used psychosis symptom data and structural connectivity in 1068 individuals from the Philadelphia Neurodevelopmental Cohort. Applying a network control theory metric called average controllability, we estimated each brain region's capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Using nonlinear regression, we determined the accuracy with which average controllability could predict PS symptoms in out-of-sample testing. We also examined the predictive performance of regional strength, which indexes only direct connections to a region, as well as several graph-theoretic measures of centrality that index indirect connectivity. Finally, we assessed how the prediction performance for PS symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex. Average controllability outperformed all other connectivity features at predicting positive PS symptoms and was the only feature to yield above-chance predictive performance. Improved prediction for average controllability was concentrated in transmodal cortex, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections through average controllability is crucial in association cortex. Examining interindividual variation in direct and indirect structural connections to transmodal cortex is crucial for accurate prediction of positive PS symptoms. [ABSTRACT FROM AUTHOR]

Our aim was to scrutinize multimorbidity in a community sample of youths (Philadelphia Neurodevelopmental Cohort) in form of co-occurrences of DSM-IV disorder symptom domains, elucidating if and when specific symptom domain interrelations emerge as mental disorder severity levels increase. We estimated four multimorbidity networks based on four severity cut-offs ('at least symptomatic', 'at least subthreshold', 'at least threshold', and 'impaired') and compared them pairwise on two measures: global network strength and network structure. We further computed community clusters for each network to detect symptom domain interrelations. Pairwise comparisons of the multimorbidity networks based on data from 9410 probands showed significant differences in global strength of the networks with the two highest severity cut-offs ('impaired' and 'at least threshold') with the at least symptomatic networks (p <.05). The networks with the three highest severity cut-offs ('impaired', 'at least threshold', and 'at least subthreshold') differed significantly (p <.001) from the at least symptomatic network regarding global network structure but did not significantly differ from each other (p >.05). We identified four common clusters in the impaired, at least threshold, and at least subthreshold networks consisting of i) domains associated with behavioral disorders; ii) domains associated with anxiety disorders (agoraphobia, social anxiety and specific phobia); iii) domains associated with anxiety/mood/eating and; iv) domains associated with mood/eating disorders. We found that major mental disorder symptom domain interrelations become consistent from a subthreshold level onwards. Findings suggest that specific multimorbidity patterns emerge as psychopathology severity levels increase. • Network analysis enables the description of complex mental multimorbidity patterns. • How multimorbidity patterns emerge at varying severity levels is unknown. • Multimorbidity patterns are more focused in higher severity level groups. • Four common multimorbidity clusters emerge at and above subthreshold levels. • Depressive symptoms are central in the networks across all severity levels. [ABSTRACT FROM AUTHOR]

Background: Suicidal behavior is highly familial. Neurocognitive deficits have been proposed as an endophenotype for suicide risk that may contribute to the familial transmission of suicide. Yet, there is a lack of research on the neurocognitive functioning of first‐degree biological relatives of suicide attempters. The aim of the present study is to conduct the largest investigation to date of neurocognitive functioning in community youth with a family history of a fatal or nonfatal suicide attempt (FH). Methods: Participants aged 8–21 years from the Philadelphia Neurodevelopmental Cohort completed detailed clinical and neurocognitive evaluations. A subsample of 501 participants with a FH was matched to a comparison group of 3,006 participants without a family history of suicide attempt (no‐FH) on age, sex, race, and lifetime depression. Results: After adjusting for multiple comparisons and including relevant clinical and demographic covariates, youth with a FH had significantly lower executive function factor scores (F[1,3432] = 6.63, p =.010) and performed worse on individual tests of attention (F[1,3382] = 7.08, p =.008) and language reasoning (F[1,3387] = 5.12, p =.024) than no‐FH youth. Conclusions: Youth with a FH show small differences in executive function, attention, and language reasoning compared to youth without a FH. Further research is warranted to investigate neurocognitive functioning as an endophenotype for suicide risk. Implications for the prevention and treatment of suicidal behaviors are discussed. [ABSTRACT FROM AUTHOR]

Little is known about the impact of family history of psychosis on youth from community samples. To fill this gap, we compared youth with a first-degree relative with psychosis spectrum symptoms (i.e. family history of psychosis spectrum symptoms, FHPS) to youth without FHPS in a cross-sectional analysis of the Philadelphia Neurodevelopmental Cohort (PNC). The PNC is a racially diverse community sample of 9498 youth ages 8-21 years old, of whom 8928 completed the Family Interview for Genetic Studies to determine FHPS status. Polygenic risk score for schizophrenia (PRSS) was available for a subsample of 4433 European Americans. FHPS youth (n = 489) constituted 5.5% of the analytic sample. After adjusting for environmental risk factors (sociodemographic variables and traumatic stressful events), FHPS youth had lower functioning on the Children's Global Assessment Scale and elevated psychosis spectrum, mood, externalizing, and fear symptoms compared to non-FHPS youth (all p < .001). In the European-American subsample, FHPS status was associated with poorer functioning and greater symptom burden in all four psychopathology domains (all p < .001), even after covarying for PRSS. Thus, ascertaining FHPS is important because it is uniquely associated with symptoms and functional impairment in community youth beyond PRS-S and the environmental risk factors we investigated. Future research identifying environmental causes of FHPS-associated impairment could inform the development of interventions for the broad array of symptoms observed in FHPS youth. [ABSTRACT FROM AUTHOR]

Structured assessment of clinical phenotypes is a burdensome procedure, largely due to the time required. One method to alleviate this is "skip-logic," which allows for portions of an interview to be skipped if initial ("screen") items are not endorsed. The bias that skip-logic introduces to resultant continuous scores is unknown and can be explored using Item Response Theory. Interview response data were simulated while varying 5 characteristics of the measures: number of screen items, difficulty (clinical severity) of the screens, difficulty of non-screen items, shape of the trait distribution, and range of discrimination parameters. The number of simulations and examinees were held constant at 2,000 and 10,000, respectively. A criterion variable correlating 0.80 with the measured trait was also simulated, and the outcome of interest was the difference between the correlations of the criterion variable and the two estimated scores (with and without skip-logic). Effects of the simulation conditions on this outcome were explored using ANOVA. All main effects and interactions were significant. The largest 2-way interaction was between number of screen items and average item discrimination, such that the number of screen items had a large effect on bias only when discrimination parameters were low. This, among other interactions explored here, suggests that skip-logic can bias results using continuous scores; however, the effects of this bias are usually inconsequential. Skip-logic in clinical assessments can introduce bias in continuous sum scores, but this bias can usually be ignored. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. Methods: 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−). Results: We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Conclusions: Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis. [ABSTRACT FROM AUTHOR]

Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive symptoms (OCS) in youth are common, have heterogeneous manifestations, and have been shown to be associated with serious psychopathology. While early-life trauma exposure is associated with increased risk for obsessive-compulsive disorder (OCD), its association with different OCS and its clinical relevance for serious psychopathology is unclear. Here we aimed to evaluate associations among traumatic stressful events (TSE), OCS, and serious psychiatric conditions in community youth.Methods: We studied nonmental-help seeking youths from the Philadelphia Neurodevelopmental Cohort (N = 7054, aged 11-21, 54% females, 52% prepubertal), assessed for lifetime TSE exposure and OCS. Regression models investigated cross-sectional associations of TSEs with OCS, and associations with depression, suicide ideation and psychosis. Models examined sex and puberty effects, controlling for age and socioeconomic status.Results: Trauma exposure was associated with higher OCS rates, especially in females (Trauma × Sex interaction Wald = 7.93, p = 0.005) and prepuberty (Trauma × Puberty interaction Wald = 7.68, p = 0.006). TSEs were associated with all OCS manifestations, most prominently with bad intrusive thoughts (odds ratio [OR] = 1.63). Assaultive TSEs, especially sexual assault, showed stronger associations with OCS compared with nonassaultive TSEs. While TSEs and OCS were independently associated with depression, suicide ideation, and psychosis, a significant interaction was observed only in association with increased rates of psychosis (Trauma × OCS interaction Wald = 5.08, p = 0.024).Conclusion: Early-life trauma is associated with OCS in a dose-response manner, more so in females and prepuberty. The trauma-OCS association varied by load, type of trauma, and by OCS subtypes. Trauma-OCS appears a detrimental combination in association with psychosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine agreement between parent and adolescent reports of adolescents' suicidal thoughts and explore demographic and clinical factors associated with agreement in a large community sample. METHODS: Participants included 5137 adolescents 11 to 17 years old (52.1% girls; 43.0% racial minority) and a collateral informant (97.2% parent or stepparent) from the Philadelphia Neurodevelopmental Cohort. Families were recruited from a large pediatric health care network. Adolescents and parents completed a clinical interview that included questions about adolescents' lifetime suicidal thoughts. RESULTS: Agreement was moderate for thoughts of killing self (κ = 0.466) and low for thoughts of death or dying (κ = 0.171). Discrepancies stemmed from both parental unawareness of suicidal thoughts reported by adolescents and adolescent denial of suicidal thoughts reported by parents. Fifty percent of parents were unaware of adolescents' thoughts of killing themselves, and 75.6% of parents were unaware of adolescents' recurrent thoughts of death. Forty-eight percent of adolescents denied thoughts of killing themselves, and 67.5% of adolescents denied thoughts of death reported by parents. Several demographic (eg, age) and clinical (eg, treatment history) characteristics were associated with agreement. CONCLUSIONS: Early identification and intervention hinge on reliable and valid assessment of suicide risk. The high prevalence of parental unawareness and adolescent denial of suicidal thoughts found in this study suggests that many adolescents at risk for suicide may go undetected. These findings have important clinical implications for pediatric settings, including the need for a multi-informant approach to suicide screening and a personalized approach to assessment based on empirically derived risk factors for unawareness and denial. [ABSTRACT FROM AUTHOR]

Background: Individuals with autism spectrum disorder (ASD) are challenged not only by the defining features of social-communication deficits and restricted repetitive behaviors, but also by a myriad of psychopathology varying in severity. Different cognitive deficits underpin these psychopathologies, which could be subjected to intervention to alter the course of the disorder. Understanding domain-specific mediating effects of cognition is essential for developing targeted intervention strategies. However, the high degree of inter-correlation among different cognitive functions hinders elucidation of individual effects. Methods: In the Philadelphia Neurodevelopmental Cohort, 218 individuals with ASD were matched with 872 non-ASD controls on sex, age, race, and socioeconomic status. Participants of this cohort were deeply and broadly phenotyped on neurocognitive abilities and dimensional psychopathology. Using structural equation modeling, inter-correlation among cognitive domains were adjusted before mediation analysis on outcomes of multi-domain psychopathology and functional level. Results: While social cognition, complex cognition, and memory each had a unique pattern of mediating effect on psychopathology domains in ASD, none had significant effects on the functional level. In contrast, executive function was the only cognitive domain that exerted a generalized negative impact on every psychopathology domain (p factor, anxious-misery, psychosis, fear, and externalizing), as well as functional level. Conclusions: Executive function has a unique association with the severity of comorbid psychopathology in ASD, and could be a target of interventions. As executive dysfunction occurs variably in ASD, our result also supports the clinical utility of assessing executive function for prognostic purposes. [ABSTRACT FROM AUTHOR]

This study examined provider and client perspectives of tele-mental health (TMH) in early psychosis care during the COVID-19 pandemic. To achieve this goal, thirty-three mental health providers and 31 clients from Pennsylvania Coordinated Specialty Care (CSC) programs completed web-based surveys assessing TMH usage, experiences, and perceptions between May and September 2020. Three additional TMH-related questions were asked two years later of PA CSC Program Directors between Feb and March 2022. Descriptive statistics characterized responses. Open-ended items were coded and grouped into themes for qualitative synthesis. As early as mid-2020, participants reported extensive use of TMH technologies, including telephone and video visits. Although most providers and clients preferred in-person care to TMH, most clients still found TMH to be comparable to or better than in-person care; 94% of clients indicated interest in future TMH services. Providers also noted more successes than challenges with TMH. Nine themes emerged regarding provider-perceived client characteristics that could benefit from TMH and were grouped into two categories: client-level (access to technology, comfort with technology, transportation, young age, symptom severity, functioning level, motivation for treatment adherence) and interpersonal-level (external support systems and engagement with program prior to the pandemic) characteristics. Two years later, program directors reported continued perceived advantages of TMH in CSCs, although some barriers persisted. Despite the unexpected shift to TMH in early psychosis programs during the COVID-19 pandemic, findings indicated a relatively positive transition to TMH and perceived promise of TMH as a sustained part of routine care. [ABSTRACT FROM AUTHOR]

Abstract Models for early psychosis intervention often involve shared decision-making among patients, their caregivers, and clinicians. However, this process rests on a shared understanding of constructs, experiences, and language. This study examined how various aspects of early psychosis care were conceptualized by those involved in the help-seeking process, and the extent to which their perceptions aligned with one another. We conducted a free listing study to systematically explore perceptions of the help-seeking process and management of psychosis-related symptoms among a sample of 65 patients, caregivers, and clinicians at an early psychosis intervention clinic. Results indicated varying levels of agreement between different roles on getting or giving help, taking medications, factors influencing symptom management, and thoughts regarding the future. These findings highlight important differences and emphasize a need for further exploration of how stakeholder perceptions may influence decisions surrounding the care of individuals experiencing early psychosis. [ABSTRACT FROM AUTHOR]

Background Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and nondeleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity. Methods ND youths ( n = 150) ages 9 to 24 years were matched to 22q11DS individuals ( n = 150) on age and sex, stratifying for presence of psychosis spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes, and for attention-deficit/hyperactivity, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differs from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis. Results Onset of psychosis proneness was similar among 22q11DS (mean: 11.0 years) and ND (mean: 12.1 years) individuals. Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND individuals were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but it did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis spectrum 22q11DS; substance-related disorders were more likely in ND. Global assessment of function was similar in 22q11DS and ND individuals, except among those with low total Structured Interview for Prodromal Syndromes scores. Conclusions Individuals with 22q11DS share overarching similarities with ND individuals in psychosis symptoms and age of onset for psychosis proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study.Methods: A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania's Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains. Mixed effects regression models tested association and familiality.Results: Compared to those without mood disorders, participants with BP-I had increased accuracy in complex cognition, while participants with MDD were more accurate in emotion recognition. There was also a significant familial association for accuracy of complex cognition. Mood disorder subgroups did not differ in performance speed in any of the domains.Limitations: The small number of BP-I cases, and family size limited the statistical power of these analyses, and the cross-sectional assessment of neurocognitive function precluded our ability to determine whether performance precedes or post dates onset of disorder.Conclusions: This is one of the few community-based family studies of potential neurocognitive endophenotypes that includes the full range of mood disorder subgroups. There were few differences in neurocognitive function except enhanced accuracy in specific domains among those with BP-I and MDD. The differential findings across specific mood disorder subgroups substantiate their heterogeneity in other biologic and endophenotypic domains. [ABSTRACT FROM AUTHOR]

Inclusion of collateral informant reports is common in adolescent psychopathology research and clinical assessment, yet few studies have examined agreement on ratings of adolescent substance use or factors that may be associated with reporter agreement. The present study aimed to extend prior work on the correspondence between adolescent and informant reports of adolescent substance use with data from a large (n=5214), diverse, community-based sample of youth aged 11-17 (mean age=14.53, SD=1.98; 52% female). Specifically, we examined: (a) agreement between adolescent and collateral informant reports of adolescent use of alcohol, marijuana, cocaine, inhalants, and stimulants and (b) potential correlates of reporter agreement. Agreement ranged from low (κ=0.007, p=0.053) for inhalant use to moderate (κ=0.414, p<0.001) for marijuana use. Disagreements were mainly driven by collateral underestimation of adolescent substance use. Older adolescent age was associated with poorer agreement across all substances (Odds Ratios [ORs]≤0.80, ps<0.05) except inhalants (OR=1.28, p<0.001). Reporter agreement on alcohol and marijuana use was lower for male than female adolescents (ORs≤0.85, ps<0.05). Adolescent psychopathology was associated with poorer agreement on all substances (ORs≤0.62, ps<0.01). For alcohol and marijuana, past year frequency of use was associated with better reporter agreement (ORs≥1.54, ps<0.001). For marijuana, older age at first use was related to poorer agreement (OR=0.81, p=0.01). Our results suggest that collateral reports of adolescent substance use may be ineffective proxies for adolescent self-reports in community samples, particularly for low base rate substances. Findings also highlight important factors to consider when collecting substance use information from multiple informants. [ABSTRACT FROM AUTHOR]

Aim: The Pennsylvania first episode psychosis program evaluation (PA‐FEP‐PE) core assessment battery was developed as a standard and comprehensive clinical assessment and data collection tool in Pennsylvania coordinated specialty care programs (CSC). To reduce administrative time and maximize clinical utility by maintaining acceptable levels of precision, we aimed to generate a short form using item response theory (IRT)‐based computer‐adaptive test (CAT) simulation and analyse the implementation and acceptability of the short form among providers from PA‐CSC. Methods: FEP participants (n = 759; age 14–36) from nine coordinated specialty care programs completed 156 items drawn from the PA‐FEP‐PE battery. Multidimensional IRT‐based CAT simulations were used to select the best PA‐FEP‐PE items for abbreviated forms. Results: A 67‐item PA‐FEP‐PE short form was developed to capture six factors: (1) positive affect and surgency (with negative loadings on Anxious‐Misery items); (2) psychiatric services satisfaction; (3) antipsychotic side effect severity; (4) family turmoil and associated traumas; (5) trauma load; and (6) psychosis. The total number of items was reduced more than 50% in the PA‐FEP‐PE shortened forms. The short form demonstrated good psychometric properties, and it was well accepted by our providers in the implementation. Conclusions: The empirical derivation and implementation of abbreviated measures of key domains and constructs in FEP care have streamlined and facilitated PA‐FEP program evaluation. Our work supports potential application of IRT based methods to empirically reduce core assessment battery measures in large‐scale data collection efforts such as in the Early Psychosis Intervention Network. [ABSTRACT FROM AUTHOR]

The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in the association cortex, implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. The authors studied 790 youths ages 8 to 23 years who had 27 minutes of high-quality functional magnetic resonance imaging data as part of the Philadelphia Neurodevelopmental Cohort. Four correlated dimensions were estimated using a confirmatory correlated traits factor analysis on 112 item-level clinical symptoms, and one overall psychopathology factor with 4 orthogonal dimensions were extracted using a confirmatory factor analysis. Spatially regularized nonnegative matrix factorization was used to identify 17 individual-specific functional networks for each participant. Partial least square regression with split-half cross-validation was conducted to evaluate to what extent the topography of personalized functional networks encodes major dimensions of psychopathology. Personalized functional network topography significantly predicted unseen individuals' major dimensions of psychopathology, including fear, psychosis, externalizing, and anxious-misery. Reduced representation of association networks was among the most important features for the prediction of all 4 dimensions. Further analysis revealed that personalized functional network topography predicted overall psychopathology (r = 0.16, permutation testing p <.001), which drove prediction of the 4 correlated dimensions. These results suggest that individual differences in functional network topography in association networks is related to overall psychopathology in youth. Such results underscore the importance of considering functional neuroanatomy for personalized diagnostics and therapeutics in psychiatry. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the amount of energy required to propagate dynamics across the sensory-fugal axis using network control theory. Topics discussed include mapping trans-hierachical state transitions, gradient of cytoarchitecture constrains the flow of activity over the cortex, and asymmetries in trans-hierarchical state transitions refined throughout the development.

Precision psychiatry is an emerging field with transformative opportunities for mental health. However, the use of clinical prediction models carries unprecedented ethical challenges, which must be addressed before accessing the potential benefits of precision psychiatry. This critical review covers multidisciplinary areas, including psychiatry, ethics, statistics and machine-learning, healthcare and academia, as well as input from people with lived experience of mental disorders, their family, and carers. We aimed to identify core ethical considerations for precision psychiatry and mitigate concerns by designing a roadmap for research and clinical practice. We identified priorities: learning from somatic medicine; identifying precision psychiatry use cases; enhancing transparency and generalizability; fostering implementation; promoting mental health literacy; communicating risk estimates; data protection and privacy; and fostering the equitable distribution of mental health care. We hope this blueprint will advance research and practice and enable people with mental health problems to benefit from precision psychiatry. [ABSTRACT FROM AUTHOR]

Objective: Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present.Method: The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). The effect of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) was examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses.Results: Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo-opercular control network, including the frontal pole, cingulate cortex, and anterior insula. In addition, psychosis-spectrum symptoms were associated with hypoactivation of the left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypoactivation of the frontoparietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyperactivation of the executive network.Conclusions: These findings provide novel evidence that common and dissociable deficits within the brain's executive system are present in association with dimensions of psychopathology in youth. [ABSTRACT FROM AUTHOR]