Racial and ethnic inequities in psychiatric inpatient building and unit assignment.

Racism is a social determinant of mental health which has a disproportionally negative impact on the experiences of psychiatric inpatients of color. Distinct differences in the physical space and clinical settings of two inpatient buildings at a hospital system in the tristate (New York, New Jersey, Connecticut) area of the United States led to the present investigation of racial inequities in the assignment of patients to specific buildings and units. Archival electronic medical record data were analyzed from over 18,000 unique patients over a period of six years. Hierarchical logistic regression analyses were conducted with assigned building (old vs. new building) as the binary outcome variable. Non-Hispanic White patients were set as the reference group. Black, Hispanic/Latinx, and Asian patients were significantly less likely to be assigned to better resourced units in the new building. When limiting the analysis to only general adult units, Black and Hispanic/Latinx patients were significantly less likely to be assigned to units in the new building. These results suggest ethnoracial inequities in patient assignment to buildings which differed in clinical and physical conditions. The findings serve as a call to action for hospital systems to examine the ways in which structural racism impact clinical care.

Race-Based Disparities in the Frequency and Duration of Restraint Use in a Psychiatric Inpatient Setting.

OBJECTIVE: Patients' race and age have each been identified as risk factors for experiencing restraint events during psychiatric hospitalization. Restraint duration is also an important variable in determining disparities in treatment. To the authors' knowledge, no studies to date have examined the effect of the interaction of race and age on restraint use and duration in inpatient psychiatric settings. This retrospective chart review of electronic medical records of patients admitted between 2012 and 2019 sought to examine whether race and age interacted in predicting differences in the use and duration of restraints in a psychiatric inpatient setting. METHODS: Logistic and hierarchical regression analyses were conducted on data from a sample of 29,739 adolescent (ages 12-17 years) and adult (ages ≥18 years) inpatients to determine whether the interaction of race and age group (adolescent or adult) significantly predicted a restraint event or differences in restraint duration. RESULTS: Black (adjusted OR [AOR]=1.85) and multiracial (AOR=1.36) patients were more likely to experience a restraint event than were their White peers. Black race was also significantly (p=0.001) associated with longer restraint duration. No significant interaction was detected between race and age in predicting restraint events or duration. CONCLUSIONS: Although the interaction between race and age did not predict restraint events or duration, the findings indicate racial disparities in the frequency and duration of restraint events among Black and multiracial individuals and may inform efforts to reduce these events.

Characterizing and detecting delirium with clinical and computational measures of speech and language disturbance.

BACKGROUND: Delirium is a critically underdiagnosed syndrome of altered mental status affecting more than 50% of older adults admitted to hospital. Few studies have incorporated speech and language disturbance in delirium detection. We sought to describe speech and language disturbances in delirium, and provide a proof of concept for detecting delirium using computational speech and language features. METHODS: Participants underwent delirium assessment and completed language tasks. Speech and language disturbances were rated using standardized clinical scales. Recordings and transcripts were processed using an automated pipeline to extract acoustic and textual features. We used binomial, elastic net, machine learning models to predict delirium status. RESULTS: We included 33 older adults admitted to hospital, of whom 10 met criteria for delirium. The group with delirium scored higher on total language disturbances and incoherence, and lower on category fluency. Both groups scored lower on category fluency than the normative population. Cognitive dysfunction as a continuous measure was correlated with higher total language disturbance, incoherence, loss of goal and lower category fluency. Including computational language features in the model predicting delirium status increased accuracy to 78%. LIMITATIONS: This was a proof-of-concept study with limited sample size, without a set-aside cross-validation sample. Subsequent studies are needed before establishing a generalizable model for detecting delirium. CONCLUSION: Language impairments were elevated among patients with delirium and may also be used to identify subthreshold cognitive disturbances. Computational speech and language features are promising as accurate, noninvasive and efficient biomarkers of delirium.

Latent Factors of Language Disturbance and Relationships to Quantitative Speech Features.

BACKGROUND AND HYPOTHESIS: Quantitative acoustic and textual measures derived from speech ("speech features") may provide valuable biomarkers for psychiatric disorders, particularly schizophrenia spectrum disorders (SSD). We sought to identify cross-diagnostic latent factors for speech disturbance with relevance for SSD and computational modeling. STUDY DESIGN: Clinical ratings for speech disturbance were generated across 14 items for a cross-diagnostic sample (N = 334), including SSD (n = 90). Speech features were quantified using an automated pipeline for brief recorded samples of free speech. Factor models for the clinical ratings were generated using exploratory factor analysis, then tested with confirmatory factor analysis in the cross-diagnostic and SSD groups. The relationships between factor scores and computational speech features were examined for 202 of the participants. STUDY RESULTS: We found a 3-factor model with a good fit in the cross-diagnostic group and an acceptable fit for the SSD subsample. The model identifies an impaired expressivity factor and 2 interrelated disorganized factors for inefficient and incoherent speech. Incoherent speech was specific to psychosis groups, while inefficient speech and impaired expressivity showed intermediate effects in people with nonpsychotic disorders. Each of the 3 factors had significant and distinct relationships with speech features, which differed for the cross-diagnostic vs SSD groups. CONCLUSIONS: We report a cross-diagnostic 3-factor model for speech disturbance which is supported by good statistical measures, intuitive, applicable to SSD, and relatable to linguistic theories. It provides a valuable framework for understanding speech disturbance and appropriate targets for modeling with quantitative speech features.

Clinical and computational speech measures are associated with social cognition in schizophrenia spectrum disorders.

In this study, we compared three domains of social cognition (emotion processing, mentalizing, and attribution bias) to clinical and computational language measures in 63 participants with schizophrenia spectrum disorders. Based on the active inference model for discourse, we hypothesized that emotion processing and mentalizing, but not attribution bias, would be related to language disturbances. Clinical ratings for speech disturbance assessed disorganized and underproductive dimensions. Computational features included speech graph metrics, use of modal verbs, use of first-person pronouns, cosine similarity of adjacent utterances, and measures of sentiment; these were represented by four principal components. We found that higher clinical ratings for disorganized speech were predicted by greater impairments in both emotion processing and mentalizing, and that these relationships remained significant when accounting for demographic variables, overall psychosis symptoms, and verbal ability. Similarly, a computational speech component reflecting insular speech was consistently predicted by impairment in emotion processing. There were notable trends for computational speech components reflecting underproductive speech and decreased content-rich speech predicting mentalizing ability. Exploratory longitudinal analyses in a small subset of participants (n = 17) found that improvements in both emotion processing and mentalizing predicted improvements in disorganized speech. Attribution bias did not demonstrate strong relationships with language measures. Altogether, our findings are consistent with the active inference model of discourse and suggest greater emphasis on treatments that target social cognitive and language systems.

Who does what to whom? graph representations of action-predication in speech relate to psychopathological dimensions of psychosis.

Graphical representations of speech generate powerful computational measures related to psychosis. Previous studies have mostly relied on structural relations between words as the basis of graph formation, i.e., connecting each word to the next in a sequence of words. Here, we introduced a method of graph formation grounded in semantic relationships by identifying elements that act upon each other (action relation) and the contents of those actions (predication relation). Speech from picture descriptions and open-ended narrative tasks were collected from a cross-diagnostic group of healthy volunteers and people with psychotic or non-psychotic disorders. Recordings were transcribed and underwent automated language processing, including semantic role labeling to identify action and predication relations. Structural and semantic graph features were computed using static and dynamic (moving-window) techniques. Compared to structural graphs, semantic graphs were more strongly correlated with dimensional psychosis symptoms. Dynamic features also outperformed static features, and samples from picture descriptions yielded larger effect sizes than narrative responses for psychosis diagnoses and symptom dimensions. Overall, semantic graphs captured unique and clinically meaningful information about psychosis and related symptom dimensions. These features, particularly when derived from semi-structured tasks using dynamic measurement, are meaningful additions to the repertoire of computational linguistic methods in psychiatry.

Feasibility of Mobile Health and Social Media-Based Interventions for Young Adults With Early Psychosis and Clinical Risk for Psychosis: Survey Study.

BACKGROUND: Digital technology, the internet, and social media are increasingly investigated as promising means for monitoring symptoms and delivering mental health treatment. These apps and interventions have demonstrated preliminary acceptability and feasibility, but previous reports suggest that access to technology may still be limited among individuals with psychotic disorders relative to the general population. OBJECTIVE: We evaluated and compared access to and use of technology and social media in young adults with psychotic disorders (PD), young adults with clinical risk for psychosis (CR), and psychosis-free youths (PF). METHODS: Participants were recruited through a coordinated specialty care clinic dedicated toward early psychosis as well as ongoing studies. We surveyed 21 PD, 23 CR, and 15 PF participants regarding access to technology and use of social media, specifically Facebook and Twitter. Statistical analyses were conducted in R. Categorical variables were compared among groups using Fisher exact test, continuous variables were compared using 1-way ANOVA, and multiple linear regressions were used to evaluate for covariates. RESULTS: Access to technology and social media were similar among PD, CR, and PF participants. Individuals with PD, but not CR, were less likely to post at a weekly or higher frequency compared to PF individuals. We found that decreased active social media posting was unique to psychotic disorders and did not occur with other psychiatric diagnoses or demographic variables. Additionally, variation in age, sex, and White versus non-White race did not affect posting frequency. CONCLUSIONS: For young people with psychosis spectrum disorders, there appears to be no "technology gap" limiting the implementation of digital and mobile health interventions. Active posting to social media was reduced for individuals with psychosis, which may be related to negative symptoms or impairment in social functioning.

Metabolic disturbances, hemoglobin A1c, and social cognition impairment in Schizophrenia spectrum disorders.

Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HbA1c) > 6.5%. Tasks assessed emotion processing, theory of mind, and social perception. Functional connectivity within and between social cognitive networks was measured during a naturalistic social task. Among SSD, a significant inverse relationship was found between social cognition and cumulative metabolic burden (ß = -0.38, p < 0.001) and HbA1c (ß = -0.37, p < 0.001). The relationship between social cognition and HbA1c was robust across domains and measures of social cognition and after accounting for age, sex, race, non-social neurocognition, hospitalization, and treatment with different antipsychotic medications. Negative connectivity between affect sharing and motor resonance networks was a partial mediator of this relationship across SSD and HC groups (ß = -0.05, p = 0.008). There was a group x HbA1c effect indicating that SSD participants were more adversely affected by increasing HbA1c. Thus, we provide the first report of a robust relationship in SSD between social cognition and abnormal glucose metabolism. If replicated and found to be causal, insulin sensitivity and blood glucose may present as promising targets for improving social cognition, functional outcomes, and quality of life in SSD.

Natural language processing methods are sensitive to sub-clinical linguistic differences in schizophrenia spectrum disorders.

Computerized natural language processing (NLP) allows for objective and sensitive detection of speech disturbance, a hallmark of schizophrenia spectrum disorders (SSD). We explored several methods for characterizing speech changes in SSD (n = 20) compared to healthy control (HC) participants (n = 11) and approached linguistic phenotyping on three levels: individual words, parts-of-speech (POS), and sentence-level coherence. NLP features were compared with a clinical gold standard, the Scale for the Assessment of Thought, Language and Communication (TLC). We utilized Bidirectional Encoder Representations from Transformers (BERT), a state-of-the-art embedding algorithm incorporating bidirectional context. Through the POS approach, we found that SSD used more pronouns but fewer adverbs, adjectives, and determiners (e.g., "the," "a,"). Analysis of individual word usage was notable for more frequent use of first-person singular pronouns among individuals with SSD and first-person plural pronouns among HC. There was a striking increase in incomplete words among SSD. Sentence-level analysis using BERT reflected increased tangentiality among SSD with greater sentence embedding distances. The SSD sample had low speech disturbance on average and there was no difference in group means for TLC scores. However, NLP measures of language disturbance appear to be sensitive to these subclinical differences and showed greater ability to discriminate between HC and SSD than a model based on clinical ratings alone. These intriguing exploratory results from a small sample prompt further inquiry into NLP methods for characterizing language disturbance in SSD and suggest that NLP measures may yield clinically relevant and informative biomarkers.

Meta-analysis of olfactory dysfunction in 22q11.2 deletion syndrome.

A quantitative review of literature concerning olfactory function in 22q11.2 deletion syndrome (22q11DS) patients was performed detailing the scope/magnitude of deficits and probing possible moderators. We searched MEDLINE, EMBASE and PubMed to identify studies for inclusion. Effect sizes were based on differences in psychophysical olfactory tests between 22q11DS patients (n = 194) and typically developing comparison subjects (n = 466). 22q11DS patients exhibited marked olfactory dysfunction (d=-1.11, 95% CI=-1.29<δ<-0.92) that was homogeneous (p = 0.86). Diffuse olfactory deficits were seen which were not moderated by age or sex. 22q11DS patients exhibit large/diffuse deficits in olfactory function that are of a similar magnitude to observed neuropsychological impairments.

Theatre improvisation training to promote social cognition: A novel recovery-oriented intervention for youths at clinical risk for psychosis.

AIM: Few interventions address social cognition or functioning in individuals at clinical risk (CR) for psychosis. Theatre Improvisation Training to Promote Social Cognition (TIPS) is a manualized intervention based on drama therapy. We aim to describe TIPS, evaluate feasibility and acceptability, and present a preliminary investigation of outcomes in a quasi-experimental design. METHODS: Thirty-six CR participants (15-25 years) were ascertained from the Philadelphia Neurodevelopmental Cohort. Twenty-six completed the TIPS protocol: 18 weekly 2-hour group sessions led by a theatre director and actor-assistant. Participants engaged in collaborative acting and improvisation exercises. Baseline and follow-up assessments included the Clinical Assessment Interview for Negative Symptoms (CAINS), Structured Interview for Prodromal Syndromes, Global Assessment of Functioning (GAF) and Penn Computerized Neurocognitive Battery (CNB), which includes social cognitive tests. Acceptability was assessed using focus groups. Preliminary outcomes were compared to CR controls who were not enrolled in the study but completed follow-up assessments using the same methods. RESULTS: There were no significant differences in baseline demographics, psychosis symptoms, or cognition between those who did and did not complete the protocol. Overall, TIPS was considered feasible and acceptable among CR. Preliminary outcomes suggest that TIPS may be effective in improving positive and negative psychosis-spectrum symptoms and GAF, but not performance on facial emotion processing. CONCLUSIONS: TIPS is a promising and acceptable intervention that may improve symptoms and functioning in CR while providing a framework for participants to develop more empowered and confident ways of relating to others. Larger randomized controlled trials investigating TIPS efficacy are warranted.

Characteristics of youth with reported family history of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort.

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.

Musical auditory processing, cognition, and psychopathology in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with impairment in multiple domains of cognition and risk for several psychiatric disorders. Musical auditory processing is highly heritable, and is impaired in individuals with schizophrenia and other neurodevelopmental disorders, but has never been studied in 22q11DS, notwithstanding anecdotal evidence of its sparing. We aimed to characterize musical auditory processing in 22q11DS and explore potential relationships with other cognitive domains, musical engagement, and psychiatric disorders. The Distorted Tunes Task and Global Musical Sophistication Index were used to assess pitch discrimination and general musical engagement in 58 individuals with 22q11DS aged 8-29 years. Psychopathology was assessed with sections from the modified Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Structured Interview for Prodromal Syndromes. The Penn computerized neurocognitive battery (CNB) examined four domains of cognition (executive functioning, episodic memory, complex cognition, and social cognition). Significant musical auditory processing impairment and reduced musical engagement were found in individuals with 22q11DS. However, deficits in musical auditory processing were not associated with reduced musical engagement. After covarying for age and sex, episodic memory and overall CNB performance accuracy were significantly related to performance in musical auditory processing. There were no relationships between musical auditory processing and presence of any psychiatric diagnoses. Individuals with 22q11DS experience significant deficits in musical auditory processing and reduced musical engagement. Pitch discrimination is associated with overall cognitive ability, but appears to be largely independent of psychiatric illness.

Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome.

Olfactory functioning is a promising biomarker for psychosis in 22q11.2 deletion syndrome (22q11DS) but has not been well studied to date. This is a pilot effort to evaluate the potential for tests of olfactory functioning to contribute to risk and resilience prediction in 22q11DS, and is the first study to evaluate relationships among olfactory deficits, cognition and psychosis-spectrum symptoms. Odor identification and discrimination were evaluated in 32 individuals with 22q11DS and 110 healthy comparison subjects (HC). Individuals with 22q11DS also underwent cognitive testing with the Penn Computerized Neurocognitive Battery, which evaluates executive functioning, episodic memory, complex cognition, and social cognition. Positive, negative, disorganized and general psychosis-spectrum symptoms were rated according to the Scale of Prodromal Symptoms. Age-normalized scores were calculated for odor identification and discrimination based on normative data. Both odor identification (p < 0.001, Cohen's d = -2.15, 95% CI [-2.62, -1.68]) and discrimination (p < 0.001, Cohen's d = -1.81, 95% CI [-2.26, -1.35]) were significantly impaired in 22q11DS relative to HC. There were no sex differences in either group. Neither odor identification nor discrimination was correlated with overall cognition or any specific cognitive domain in 22q11DS. Impairment in odor discrimination was correlated with higher negative and overall psychosis-spectrum symptoms. There was no significant effect of catechol-O-methyltransferase Val(158)Met genotype or presence of velopharyngeal insufficiency on olfactory functioning. Olfactory deficits, particularly olfactory discrimination, are robust in 22q11DS and appear to be independent of cognitive deficits. They are also clinically relevant and related to psychosis-spectrum symptoms. Olfactory functioning appears to be a promising biomarker for psychosis in 22q11DS.

Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome.

The prevalence of psychotic disorders in individuals with 22q11.2 Deletion Syndrome (22q11DS) reaches 25-35% in young adulthood and may provide a neurogenetic model for clinical risk of psychotic disorders in the general population. This review focuses on prospective longitudinal studies in 22q11DS, which capture fluctuations in psychosis symptoms over time and may provide insights into potential demographic, clinical, cognitive, and neuroimaging predictors of psychosis-spectrum outcomes in the general population. Findings are compared and contrasted with those from idiopathic psychosis-spectrum populations. Onset of psychotic disorders in 22q11DS can occur over a wide range of ages, peaking in late adolescence. Symptoms may be gradually progressive or episodic in nature, highlighting the importance and challenge of risk and resilience prediction models. Converging results suggest that psychosis-spectrum outcomes in 22q11DS are predicted by lower baseline functioning, higher baseline psychosis-spectrum symptoms, presence of mood disturbance or anxiety, and lower baseline and subsequent decline in global measures of cognition. Predictors of transition to threshold psychotic disorders and ages of onset are similar in idiopathic clinical risk. They also share similarly global cognitive deficits, but not to the same extent as in 22q11DS. While neuroimaging studies in idiopathic clinical risk suggest loss of prefrontal gray matter, there is no consistent evidence yet emerging in the limited literature in 22q11DS. Interventional efforts in 22q11DS aimed at halting progression to psychosis or mitigating outcomes in early psychosis may be best implemented during the adolescent age range. Collaborative longitudinal efforts may help to address existing gaps in our understanding.

Attention Deficit Hyperactivity Disorder Symptoms and Psychosis in 22q11.2 Deletion Syndrome.

OBJECTIVE: 22q11.2 Deletion Syndrome (22q11.2DS) is associated with increased risk for schizophrenia in adulthood while Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent diagnosis in childhood. Inattention symptoms are pronounced in 22q11.2DS and given that attentional impairment is a core feature of schizophrenia, inattention symptoms may reflect underlying ADHD, psychosis, or both. We investigate whether inattention is associated with psychosis in 22q11.2DS and in other groups at risk for psychosis but without the deletion (ND) (idiopathic clinical risk and first degree family members of individuals with schizophrenia). METHODS: One hundred thirty-seven individuals with 22q11.2DS (mean age: 14.0), 84 ND individuals with subthreshold psychosis (mean age: 16.9) and 31 ND individuals with family history of psychosis (mean age: 17.0) were included in the study. Psychopathology was assessed using research diagnostic assessments. RESULTS: ADHD total symptoms were associated with overall levels of subthreshold psychosis symptoms in 22q11.2DS (ß = .8, P = .04). Inattention symptoms were specifically associated with positive (ß = .5, P = .004), negative (ß = .5, P = .03), and disorganized (ß = .5, P < .001) symptoms, while hyperactivity-impulsivity symptoms were associated with disorganized symptoms (ß = .5, P = .01). The prevalence of ADHD inattention symptoms was higher in 22q11.2DS with subthreshold psychosis compared to ND individuals with subthreshold psychosis (P < .001), even when adjusting for cognitive impairment and overall psychopathology. The pattern was similar when comparing individuals with 22q11.2DS and ND individuals with family history of psychosis. CONCLUSIONS: This is the first study to examine the associations between ADHD symptoms and psychosis in 22q11.2DS. Our findings support a potentially important role of ADHD inattention symptoms in psychosis in 22q11.2DS.

Orbital floor fracture with entrapment: Imaging and clinical correlations in 45 cases.

Orbital floor fractures (OFF) with entrapment require prompt clinical and radiographic recognition for timely surgical correction. Correct CT radiographic interpretation of entrapped fractures can be subtle and thus missed. We reviewed the clinical, radiographic and intraoperative findings of 45 cases of entrapped OFF to correlate pre- and intraoperative findings with radiography. Retrospective review and statistical analysis of 45 patients with OFF using the chi squared and Kruskal-Wallis tests. Main outcome measures included patient demographics, clinical features, radiologic interpretation, intraoperative findings, and treatment outcomes. Twenty-one cases (47%) had radiologic evaluations of orbital CT scans that included commentary on possible entrapment. Intraoperatively, 16 (76%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 5 (24%) patients had incarceration of the orbital fat. Possibility of entrapment was not commented on in the radiology reports of the remaining 24 (53%) cases. Intraoperatively, 13 (54%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 11 (46%) patients had incarceration of the orbital fat. It is vital to assess the possibility of entrapment, especially in young patients, in the setting of OFF as a delay in diagnosis may lead to persistent diplopia, disfigurement, or bradycardia. Most radiology reports did not mention the possibility of entrapment in this cohort. A key concept is that entrapment occurs when any orbital tissue (muscle or fat) is trapped in the fracture site.

The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.

BACKGROUND: 22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. METHODS: We evaluated 331 individuals with 22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). RESULTS: Psychopathology in 22q11.2DS was divided into one 'general psychopathology' factor and four specific dimensions (i.e., 'anxiety', 'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the 'general psychopathology' factor. CONCLUSIONS: The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems.