Clinician-caregiver informant discrepancy is associated with sex, diagnosis age, and intervention use among autistic children.

LAY ABSTRACT: In some cases, a clinician's perceptions of a child's autism-related behaviors are not the same as the child's caregiver's perceptions. Identifying how these discrepancies relate to the characteristics of the child is critical for ensuring that diagnosis procedures are unbiased and suitable for all children. This study examined whether discrepancies between clinician and caregiver reports of autism features related to the child's sex at birth. We also explored how the discrepancies related to the age at which the child received their autism diagnosis and how much intervention they received. We found that clinicians rated autism features higher than caregivers for boys and rated autism features lower than caregivers for girls. In addition, lower clinician relative to parent ratings was related to being diagnosed at an older age and receiving less intervention. These findings suggest that there is more to learn about the presentation of autism-related behaviors in girls. When caregiver and clinician ratings of autism features do not align, it may be important to consider caregivers' ratings to obtain a more accurate picture of the child's autism features and the support they may need.

Sustained mental health and functional responses to the COVID-19 pandemic in Black and White Veterans with psychosis or recent homelessness.

The COVID-19 pandemic disproportionately impacted marginalized populations including Black Americans, people with serious mental illness, and individuals experiencing homelessness. Although the double disadvantage hypothesis would suggest that individuals with multiple minoritized statuses would experience worse psychosocial impacts from the pandemic, this may not be the case for vulnerable Black Veterans. The present study investigated the sustained mental health and functional responses to the pandemic in Black and White Veterans with psychosis or recent homelessness and in a control group of Veterans enrolled in the Department of Veterans Affairs healthcare services. Clinical interviews and questionnaires were administered remotely by telephone at five time points from May 2020 through July 2021, including a retrospective time point for March 2020 (i.e., before the pandemic started). Overall, there was a striking absence of systematic differences by race in the trajectories of psychiatric symptoms and functioning among Veterans during the study period. These findings are consistent with a report on initial responses to the pandemic that revealed only a few select differences by race among Veteran groups. The lack of racial disparities is inconsistent with the double disadvantage hypothesis. Although further investigation is needed, one possible interpretation is that the wrap-around services offered by the Veterans Health Administration may have mitigated expected differences by race among Veterans with psychosis or homelessness. Future research should continue to examine whether VA services mitigate disparities in mental health and psychosocial outcomes.

The impact of psychological strengths on Veteran populations' mental health trajectories during the COVID-19 pandemic.

PURPOSE: Mental health trajectories during the COVID-19 pandemic have been examined in Veterans with tenuous social connections, i.e., those with recent homelessness (RHV) or a psychotic disorder (PSY), and in control Veterans (CTL). We test potential moderating effects on these trajectories by psychological factors that may help individuals weather the socio-emotional challenges associated with the pandemic (i.e., 'psychological strengths'). METHODS: We assessed 81 PSY, 76 RHV, and 74 CTL over 5 periods between 05/2020 and 07/2021. Mental health outcomes (i.e., symptoms of depression, anxiety, contamination concerns, loneliness) were assessed at each period, and psychological strengths (i.e., a composite score based on tolerance of uncertainty, performance beliefs, coping style, resilience, perceived stress) were assessed at the initial assessment. Generalized models tested fixed and time-varying effects of a composite psychological strengths score on clinical trajectories across samples and within each group. RESULTS: Psychological strengths had a significant effect on trajectories for each outcome (ps < 0.05), serving to ameliorate changes in mental health symptoms. The timing of this effect varied across outcomes, with early effects for depression and anxiety, later effects for loneliness, and sustained effects for contamination concerns. A significant time-varying effect of psychological strengths on depressive symptoms was evident in RHV and CTL, anxious symptoms in RHV, contamination concerns in PSY and CTL, and loneliness in CTL (ps < 0.05). CONCLUSION: Across vulnerable and non-vulnerable Veterans, presence of psychological strengths buffered against exacerbations in clinical symptoms. The timing of the effect varied across outcomes and by group.

The Selective Social Attention task in children with autism spectrum disorder: Results from the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) feasibility study.

The Selective Social Attention (SSA) task is a brief eye-tracking task involving experimental conditions varying along socio-communicative axes. Traditionally the SSA has been used to probe socially-specific attentional patterns in infants and toddlers who develop autism spectrum disorder (ASD). This current work extends these findings to preschool and school-age children. Children 4- to 12-years-old with ASD (N = 23) and a typically-developing comparison group (TD; N = 25) completed the SSA task as well as standardized clinical assessments. Linear mixed models examined group and condition effects on two outcome variables: percent of time spent looking at the scene relative to scene presentation time (%Valid), and percent of time looking at the face relative to time spent looking at the scene (%Face). Age and IQ were included as covariates. Outcome variables' relationships to clinical data were assessed via correlation analysis. The ASD group, compared to the TD group, looked less at the scene and focused less on the actress' face during the most socially-engaging experimental conditions. Additionally, within the ASD group, %Face negatively correlated with SRS total T-scores with a particularly strong negative correlation with the Autistic Mannerism subscale T-score. These results highlight the extensibility of the SSA to older children with ASD, including replication of between-group differences previously seen in infants and toddlers, as well as its ability to capture meaningful clinical variation within the autism spectrum across a wide developmental span inclusive of preschool and school-aged children. The properties suggest that the SSA may have broad potential as a biomarker for ASD.

A Novel Psychosocial Intervention for Motivational Negative Symptoms in Schizophrenia: Combined Motivational Interviewing and CBT.

OBJECTIVE: Negative symptoms are a primary cause of disability in schizophrenia for which there are no established pharmacotherapies. This study evaluated a novel psychosocial intervention that combined two evidence-based practices-motivational interviewing and cognitive-behavioral therapy (MI-CBT)-for the treatment of motivational negative symptoms. METHODS: Seventy-nine participants with schizophrenia and moderate to severe negative symptoms were included in a randomized controlled trial comparing the 12-session MI-CBT treatment with a mindfulness control condition. Participants were assessed at three time points through the study period, which included 12 weeks of active treatment and 12 weeks of follow-up. The primary outcome measures were motivational negative symptoms and community functioning; the secondary outcomes included a posited biomarker of negative symptoms: pupillometric response to cognitive effort. RESULTS: Compared with the control group, participants in the MI-CBT group showed significantly greater improvements in motivational negative symptoms over the acute treatment period. Their gains relative to baseline were maintained at follow-up, although the differential benefit relative to control subjects was attenuated. There were nonsignificant effects toward improvements in community functioning and differential change in the pupillometric markers of cognitive effort. CONCLUSIONS: The results show that combining motivational interviewing with CBT yields improvements in negative symptoms, a feature of schizophrenia generally thought of as resistant to intervention. Motivational negative symptoms not only responded to the novel treatment, but the gains were maintained over the follow-up period. Implications for future studies and for improving the generalization of the negative symptom gains to daily functioning domains are discussed.

Evaluation of clinical assessments of social abilities for use in autism clinical trials by the autism biomarkers consortium for clinical trials.

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.

The Autism Biomarkers Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG Biomarkers.

OBJECTIVE: Numerous candidate EEG biomarkers have been put forward for use in clinical research on autism spectrum disorder (ASD), but biomarker development has been hindered by limited attention to the psychometric properties of derived variables, inconsistent results across small studies, and variable methodology. The authors evaluated the basic psychometric properties of a battery of EEG assays for their potential suitability as biomarkers in clinical trials. METHODS: This was a large, multisite, naturalistic study in 6- to 11-year-old children who either had an ASD diagnosis (N=280) or were typically developing (N=119). The authors evaluated an EEG battery composed of well-studied assays of resting-state activity, face perception (faces task), biological motion perception, and visual evoked potentials (VEPs). Biomarker psychometrics were evaluated in terms of acquisition rates, construct performance, and 6-week stability. Preliminary evaluation of use was explored through group discrimination and phenotypic correlations. RESULTS: Three assays (resting state, faces task, and VEP) show promise in terms of acquisition rates and construct performance. Six-week stability values in the ASD group were moderate (intraclass correlations ≥0.66) for the faces task latency of the P1 and N170, the VEP amplitude of N1 and P1, and resting alpha power. Group discrimination and phenotype correlations were primarily observed for the faces task P1 and N170. CONCLUSIONS: In the context of a large-scale, rigorous evaluation of candidate EEG biomarkers for use in ASD clinical trials, neural response to faces emerged as a promising biomarker for continued evaluation. Resting-state activity and VEP yielded mixed results. The study's biological motion perception assay failed to display construct performance. The results provide information about EEG biomarker performance that is relevant for the next stage of biomarker development efforts focused on context of use.

Concomitant medication use in children with autism spectrum disorder: Data from the Autism Biomarkers Consortium for Clinical Trials.

LAY ABSTRACT: Children with autism spectrum disorder are prescribed a variety of medications that affect the central nervous system (psychotropic medications) to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity of the sample and prevent contamination of biomarkers or clinical endpoints. However, this choice may significantly diminish the clinical representativeness of the sample. In a recent multisite study designed to identify biomarkers and behavioral endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, thus providing a unique opportunity to examine characteristics of psychotropic medication use in a research cohort and to guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the ABC-CT and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half of these children. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Descriptive analysis showed that children taking antipsychotics displayed a trend toward greater overall impairment. Our findings suggest that exclusion of children taking concomitant psychotropic medications in trials could limit the clinical representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options.

Stepped care for suicide prevention in teens and young adults: Design and methods of a randomized controlled trial.

BACKGROUND: Suicide is the second­leading cause of death among adolescents and young adults in the United States, with rates rising over much of the last decade. The design, testing, and implementation of interventions to prevent suicide in this population is a public health priority. This manuscript outlines the design and methods for a research study that compares two interventions aimed at reducing suicide and suicide attempts in youth. METHODS: We will enroll 300 youth aged 12-24 at high risk for suicide in this randomized controlled parallel group superiority trial. Participants will be randomly assigned to one of two study arms: (1) Zero Suicide Quality Improvement (ZSQI) implemented within the Kaiser Permanente Northwest (KPNW) health system, or (2) ZSQI plus a stepped care intervention for suicide prevention (SC-SP), where the services offered (including care management and dialectical behavior therapy [DBT]) increase based on risk level. Outcomes will be assessed at baseline, as well as 3-, 6-, and 12-months post randomization. The study was conceptualized and designed collaboratively by investigators at UCLA and KPNW. RESULTS: To be reported in future manuscripts. CONCLUSION: The main objective of the study is to determine whether the SC-SP intervention is superior to ZSQI with regard to lowering rates of fatal and nonfatal suicide attempts. Interventions that incorporate the latest research need to be designed and tested under controlled conditions to make progress toward the goal of achieving zero suicide. The results from this trial will directly inform those efforts. CLINICALTRIALS: gov, NCT03092271, https://clinicaltrials.gov/ct2/show/NCT03092271https://clinicaltrials.gov/ct2/show/NCT01379027.

The impact of the COVID-19 pandemic on mental health and functional outcomes in Veterans with psychosis or recent homelessness: A 15-month longitudinal study.

BACKGROUND: The COVID-19 pandemic has had unprecedented effects on mental health and community functioning. Negative effects related to disruption of individuals' social connections may have been more severe for those who had tenuous social connections prior to the pandemic. Veterans who have recently experienced homelessness (RHV) or have a psychotic disorder (PSY) are considered particularly vulnerable because many had poor social connections prior to the pandemic. METHODS: We conducted a 15-month longitudinal study between May 2020 -July 2021 assessing clinical (e.g., depression, anxiety) and community (e.g., social functioning, work functioning) outcomes. Eighty-one PSY, 76 RHV, and 74 Veteran controls (CTL) were interviewed over 5 assessment periods. We assessed changes in mental health and community functioning trajectories relative to pre-pandemic retrospective ratings and examined group differences in these trajectories. RESULTS: All groups had significantly increased symptoms of depression, anxiety, and concerns with contamination at the onset of the pandemic. However, RHV and PSY showed faster returns to their baseline levels compared to CTL, who took nearly 15 months to return to baseline. With regards to functioning, both RHV and PSY, but not CTL, had significant improvements in family and social networks over time. Work functioning worsened over time only in PSY, and independent living increased over time in both RHV and PSY but not CTL. CONCLUSIONS: These results reveal that vulnerable Veterans with access to VA mental health and case management services exhibited lower negative impacts of the COVID-19 pandemic on mental health and community functioning than expected.

Longitudinal trajectories of cortical development in 22q11.2 copy number variants and typically developing controls.

Probing naturally-occurring, reciprocal genomic copy number variations (CNVs) may help us understand mechanisms that underlie deviations from typical brain development. Cross-sectional studies have identified prominent reductions in cortical surface area (SA) and increased cortical thickness (CT) in 22q11.2 deletion carriers (22qDel), with the opposite pattern in duplication carriers (22qDup), but the longitudinal trajectories of these anomalies-and their relationship to clinical symptomatology-are unknown. Here, we examined neuroanatomic changes within a longitudinal cohort of 261 22q11.2 CNV carriers and demographically-matched typically developing (TD) controls (84 22qDel, 34 22qDup, and 143 TD; mean age 18.35, ±10.67 years; 50.47% female). A total of 431 magnetic resonance imaging scans (164 22qDel, 59 22qDup, and 208 TD control scans; mean interscan interval = 20.27 months) were examined. Longitudinal FreeSurfer analysis pipelines were used to parcellate the cortex and calculate average CT and SA for each region. First, general additive mixed models (GAMMs) were used to identify regions with between-group differences in developmental trajectories. Secondly, we investigated whether these trajectories were associated with clinical outcomes. Developmental trajectories of CT were more protracted in 22qDel relative to TD and 22qDup. 22qDup failed to show normative age-related SA decreases. 22qDel individuals with psychosis spectrum symptoms showed two distinct periods of altered CT trajectories relative to 22qDel without psychotic symptoms. In contrast, 22q11.2 CNV carriers with autism spectrum diagnoses showed early alterations in SA trajectories. Collectively, these results provide new insights into altered neurodevelopment in 22q11.2 CNV carriers, which may shed light on neural mechanisms underlying distinct clinical outcomes.

Racial differences in the psychosocial response to the COVID-19 pandemic in veterans with psychosis or recent homelessness.

The COVID-19 pandemic continues to disproportionately impact people of color and individuals experiencing psychosis and homelessness. However, it is unclear whether there are differences by race in psychosocial responses to the pandemic in vulnerable populations. The double jeopardy hypothesis posits that multiply marginalized individuals would experience worse psychosocial outcomes. The present study investigated the clinical and functional initial responses to the pandemic in both Black (n = 103) and White veterans (n = 98) with psychosis (PSY), recent homelessness (RHV), and in a control group (CTL) enrolled in Department of Veterans Affairs (VA) healthcare services. Clinical interviews were administered via phone at two time points: baseline (mid-May through mid-August 2020) and follow-up (mid-August through September 2020). The baseline interview also included retrospective measures of pre-COVID status from January 2020. There were no significant differences between Black and White veterans in depression, anxiety, or loneliness. However, Black veterans did endorse more fears of contamination, F(1, 196.29) = 9.48, p = .002. Across all groups, Black veterans had better family integration compared to White veterans, F(1, 199.98) = 7.62, p = .006. There were no significant differences by race in social integration, work/role productivity, or independent living. In sum, there were few significant differences between Black and White veterans in initial psychosocial response to the pandemic. The lack of racial disparities might reflect the presence of VA's wrap-around services. The findings also highlight the robust nature of social support in Black veterans, even in the context of a global pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Patterns of Intervention Utilization Among School-Aged Children with Autism Spectrum Disorder: Findings from a Multi-Site Research Consortium.

When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as "evidence-based practice" or "other interventions," reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0 to 79.3 hours/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.

Social cognition and social problem solving skills training to improve job functioning and tenure in veterans with psychotic disorders.

OBJECTIVE: Veterans with psychotic disorders often experience employment difficulties. Job tenure is highly variable with shorter tenure frequently tied to interpersonal difficulties in the workplace. The present study sought to address this problem by examining the efficacy of social cognition skills training (SCST) and social problem solving skills training (SPSST) interventions, implemented sequentially, and added to usual VA employment services (augmented vocational rehabilitation [VR]). METHOD: Participants were 91 Veterans with schizophrenia and other psychotic disorders who were recently enrolled in one of three types of VA employment services (incentive therapy, transitional work, supported employment), and randomized 1:1 to augmented VR versus control VR. Training for the augmented VR group included 12 weeks of SCST plus 6 weeks of work-related SPSST; training for the control VR group included a control intervention (symptom management training) matched in instructional format and length of training to the SCST and SPSST interventions. All participants received baseline and posttraining measures of social cognition. For those who got jobs, the primary work outcome measures were social skills work behavior and job tenure. RESULTS: Results showed a significant group x time interaction favoring the augmented VR group on measures of social cognition and social skills work behavior, but there were no significant differences in job tenure. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The findings for workplace social skills support a promising new direction for enhancing work outcomes in this population; the null effect on job tenure may have been due to high job retention rates across the three types of employment service programs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials.

BACKGROUND: Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). METHODS: The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. RESULTS: All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. LIMITATIONS: No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. CONCLUSIONS: All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

Family-focused therapy for individuals at high clinical risk for psychosis: A confirmatory efficacy trial.

AIMS: Young people with attenuated psychotic symptoms (APS), brief intermittent psychosis, and/or genetic risk and functional deterioration are at high risk for developing psychotic disorders. In a prior trial, family-focused therapy for clinical high risk youth (FFT-CHR) was more effective than brief psychoeducation in reducing APS severity over 6 months. This 7-site trial will compare the efficacy of FFT-CHR to a psychoeducational and supportive intervention (enhanced care) on APS and social functioning in CHR individuals over 18 months. METHODS: Participants (N = 220, ages 13-25 years) with a CHR syndrome will be randomly assigned to FFT-CHR (18 1-h sessions of family psychoeducation and communication/problem-solving skills training) or enhanced care (3 1-h family psychoeducational sessions followed by 5 individual support sessions), both given over 6 months. Participants will rate their weekly progress during treatment using a mobile-enhanced online platform. Family communication will be assessed in a laboratory interactional task at baseline and post-treatment. Independent evaluators will assess APS (primary outcome) and psychosocial functioning (secondary outcome) every 6 months over 18 months. RESULTS: We hypothesize that, compared to enhanced care, FFT-CHR will be associated with greater improvements in APS and psychosocial functioning over 18 months. Secondarily, improvements in family communication over 6 months will mediate the relationship between treatment condition and primary and secondary outcomes over 18 months. The effects of FFT-CHR are predicted to be greater in individuals with higher baseline risk for psychosis conversion. CONCLUSIONS: Results of the trial will inform treatment guidelines for individuals at high risk for psychosis.

Motivational and cognitive factors linked to community integration in homeless veterans: study 1 - individuals with psychotic disorders.

BACKGROUND: Little is known about the determinants of community integration (i.e. recovery) for individuals with a history of homelessness, yet such information is essential to develop targeted interventions. METHODS: We recruited homeless Veterans with a history of psychotic disorders and evaluated four domains of correlates of community integration: perception, non-social cognition, social cognition, and motivation. Baseline assessments occurred after participants were engaged in supported housing services but before they received housing, and again after 12 months. Ninety-five homeless Veterans with a history of psychosis were assessed at baseline and 53 returned after 12 months. We examined both cross-sectional and longitudinal relationships with 12-month community integration. RESULTS: The strongest longitudinal association was between a baseline motivational measure and social integration at 12 months. We also observed cross-sectional associations at baseline between motivational measures and community integration, including social, work, and independent living. Cross-lagged panel analyses did not suggest causal associations for the motivational measures. Correlations with perception and non-social cognition were weak. One social cognition measure showed a significant longitudinal correlation with independent living at 12 months that was significant for cross-lagged analysis, consistent with a causal relationship and potential treatment target. CONCLUSIONS: The relatively selective associations for motivational measures differ from what is typically seen in psychosis, in which all domains are associated with community integration. These findings are presented along with a partner paper (Study 2) to compare findings from this study to an independent sample without a history of psychotic disorders to evaluate the consistency in findings regarding community integration across projects.

Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia.

OBJECTIVE: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients. METHODS: Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB). RESULTS: ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage. CONCLUSIONS: Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.

Motivational and cognitive factors linked to community integration in homeless veterans: Study 2 - clinically diverse sample.

BACKGROUND: In an initial study (Study 1), we found that motivation predicted community integration (i.e. functional recovery) 12 months after receiving housing in formerly homeless Veterans with a psychotic disorder. The current study examined whether the same pattern would be found in a broader, more clinically diverse, homeless Veteran sample without psychosis. METHODS: We examined four categories of variables as potential predictors of community integration in non-psychotic Veterans: perception, non-social cognition, social cognition, and motivation at baseline (after participants were engaged in a permanent supported housing program but before receiving housing) and a 12-month follow-up. A total of 82 Veterans had a baseline assessment and 41 returned for testing after 12 months. RESULTS: The strongest longitudinal association was between an interview-based measure of motivation (the motivation and pleasure subscale from the Clinical Assessment Interview for Negative Symptoms) at baseline and measures of social integration at 12 months. In addition, cross-lagged panel analyses were consistent with a causal influence of general psychiatric symptoms at baseline driving social integration at 12 months, and reduced expressiveness at baseline driving independent living at 12 months, but there were no significant causal associations with measures of motivation. CONCLUSIONS: The findings from this study complement and reinforce those in Veterans with psychosis. Across these two studies, our findings suggest that motivational factors are associated at baseline and at 12 months and are particularly important for understanding and improving community integration in recently-housed Veterans across psychiatric diagnoses.