Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS), but may represent a unique subgroup with greater susceptibility for disease onset and worsened symptomatology and progression, which could potentially derive from exaggerated neurodevelopmental abnormalities. Neurobiological explanations of schizophrenia have emphasized the involvement of deep-brain structures, particularly alterations of the thalamus, which have been linked to core features of the disorder. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS subjects and determine whether unique behavioral profiles related to these differences. It was hypothesized abnormal thalamic shape would be observed in anterior, mediodorsal and pulvinar regions in both schizophrenia groups relative to control subjects, but exacerbated in EOS. Magnetic resonance T1-weighted images were collected from adult individuals with EOS (n = 28), AOS (n = 33), and healthy control subjects (n = 60), as well as collection of clinical and cognitive measures. Large deformation high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. General linear models were used to compare groups on surface shape features, and Pearson correlations were used to examine relationships between thalamic shape and behavioral measures. Results revealed both EOS and AOS groups demonstrated significant abnormal shape of anterior, lateral and pulvinar thalamic regions relative to CON (all p < 0.007). Relative to AOS, EOS exhibited exacerbated abnormalities in posterior lateral, mediodorsal and lateral geniculate thalamic regions (p = 0.003). Thalamic abnormalities related to worse episodic memory in EOS (p = 0.03) and worse working memory (p = 0.047) and executive functioning (p = 0003) in AOS. Overall, findings suggest thalamic abnormalities are a prominent feature in both early- and late-onset schizophrenia, but exaggerated in EOS and have different brain-behavior profiles for each. The persistence of these abnormalities in adult EOS patients suggests they may represent markers of disrupted neurodevelopment that uniquely relate to the clinical and cognitive aspects of the illness.

We have previously shown that schizophrenia (SCZ) participants with high community functioning demonstrate better verbal working memory (vWM) performance relative to those with low community functioning. In the present study, we investigated whether neuroanatomical differences in regions supporting vWM also exist between schizophrenia groups that vary on community functioning. Utilizing magnetic resonance imaging, shape features of deep-brain nuclei known to be involved in vWM were calculated in samples of high functioning (HF-SCZ, n = 23) and low functioning schizophrenia participants (LF-SCZ, n = 18), as well as in a group of healthy control participants (CON, n = 45). Large deformation diffeomorphic metric mapping was employed to characterize surface anatomy of the caudate nucleus, globus pallidus, hippocampus, and thalamus. Statistical analyses involved linear mixed-effects models and vertex-wise contrast mapping to assess between-group differences in structural shape features, and Pearson correlations to evaluate relationships between shape metrics and vWM performance. We found significant between-group main effects in deep-brain surface anatomy across all structures. Post-hoc comparisons revealed HF-SCZ and LF-SCZ groups significantly differed on both caudate and hippocampal shape, however, significant correlations with vWM were only observed in hippocampal shape for both SCZ groups. Specifically, more abnormal hippocampal deformation was associated with lower vWM suggesting hippocampal shape is both a neural substrate for vWM deficits and a potential biomarker to predict or monitor the efficacy of cognitive rehabilitation. These findings add to a growing body of literature related to functional outcomes in schizophrenia by demonstrating unique shape patterns across the spectrum of community functioning in SCZ.

BACKGROUND:Effective and efficient implementation of the Collaborative Care Model (CoCM) for depression and anxiety is imperative for program success. Studies examining barriers to implementation often omit patient perspectives.OBJECTIVES:To explore experiences and attitudes of eligible patients referred to CoCM who declined participation or were unable to be reached, and identify implementation barriers to inform strategies.DESIGN:Convergent mixed-methods study with a survey and interview.PARTICIPANTS:Primary care patients at an academic medical center who were referred to a CoCM program for anxiety and depression by their primary care clinician (PCC) but declined participation or were unable to be reached by the behavioral health care manager to initiate care (n = 80). Interviews were conducted with 45 survey respondents.MAIN MEASURES:Survey of patients' referral experiences and behavioral health preferences as they related to failing to enroll in the program. Interview questions were developed using the Consolidated Framework for Implementation Research version 2.0 (CFIR 2.0) to identify implementation barriers to enrollment.KEY RESULTS:Survey results found that patients were uncertain about insurance coverage, did not understand the program, and felt services were not necessary. Referred patients who declined participation were concerned about how their mental health information would be used and preferred treatment without medication. Men agreed more that they did not need services. Qualitative results exhibited a variety of implementation determinants (n = 23) across the five CFIR 2.0 domains. Barriers included mental health stigma, perceiving behavioral health as outside of primary care practice guidelines, short or infrequent primary care appointments, prioritizing physical health over mental health, receiving inaccurate program information, low motivation to engage, and a less established relationship with their PCC.CONCLUSIONS:Multiple barriers to enrollment led to failing to link patients to care, which can inform implementation strategies to address the patient-reported experiences and concerns.

Background In this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery. Methods Data were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0–63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13. Results Beck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88–98% at baseline and 69–79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention ( p = 0.017), memory ( p = 0.049), verbal fluency ( p = 0.010), processing speed ( p = 0.017), and fine motor speed ( p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression ( p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery. Conclusions The results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life. Trial Registration www.clinicaltrials.gov, NCT00981474 (parent study).

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta‐analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1‐weighted structural MRI scans. Mass univariate meta‐analyses revealed more‐concave‐than‐convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more‐convex‐than‐concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta‐analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Background: The Collaborative Care Model (CoCM) is a well-established treatment for depression in primary care settings. The critical drivers and specific strategies for improving implementation and sustainment are largely unknown. Rigorous pragmatic research is needed to understand CoCM implementation processes and outcomes. Methods: This study is a hybrid Type 2 randomized roll-out effectiveness-implementation trial of CoCM in 11 primary care practices affiliated with an academic medical center. The Collaborative Behavioral Health Program (CBHP) was developed as a means of improving access to effective mental health services for depression. Implementation strategies are provided to all practices. Using a sequential mixed methods approach, we will assess key stakeholders' perspectives on barriers and facilitators of implementation and sustainability of CBHP. The speed and quantity of implementation activities completed over a 30-month period for each practice will be assessed. Economic analyses will be conducted to determine the budget impact and cost offset of CBHP in the healthcare system. We hypothesize that CBHP will be effective in reducing depressive symptoms and spillover effects on chronic health conditions. We will also examine differential outcomes among racial/ethnic minority patients. Discussion: This study will elucidate critical drivers of successful CoCM implementation. It will be among the first to conduct economic analyses on a fee-for-service model utilizing billing codes for CoCM. Data may inform ways to improve implementation efficiency with an optimization approach to successive practices due to the roll-out design. Changes to the protocol and current status of the study are discussed.

There is growing evidence that schizophrenia and schizoaffective disorder represent closely related syndromes that vary in severity along a neurobiological continuum. In the present study, volume and shape of the basal ganglia was examined in people with schizophrenia and schizoaffective disorder relative to healthy controls and hypothesized that unique neuroanatomical differences would be observed in each patient group. Magnetic resonance 1.5T images were obtained from schizophrenia (n = 47), schizoaffective disorder (n = 15), and from healthy control (n = 42) participants, matched for age, gender, parental socioeconomic status, and race. The caudate, putamen, and globus pallidus were characterized using high-dimensional brain mapping procedures (Csernansky et al., 2004b). Results revealed significant shape deformations between schizophrenia and schizoaffective disorder that also differed from control subjects. Relative to schizophrenia, schizoaffective subjects showed exaggerated inward deformations indicative of localized volume loss in subregions of the caudate, putamen, and globus pallidus (all p < 0.001). These shape features correlated with mental flexibility and negative symptoms in schizophrenia (all p < 0.05), but not schizoaffective disorder. To the extent that differences in important basal ganglia substructures reflect biological heterogeneity among these two psychotic illnesses, this data could prove useful in improving diagnostic precision, as well as informing the affective component of mental illness.

To the Editors: P ERSERIS, a once-monthly, subcutaneous, extended-release risperidone formulation, was approved by the Food and Drug Administration (FDA) in 2018 for treating schizophrenia in adults based on the positive results of a pivotal 8-week, phase 3, double-blind, placebo-controlled inpatient study (NCT02109562). In this study, both doses of the extended-release risperidone formulation were found to be statistically superior to placebo on the primary and secondary end points. In addition, a 52-week open-label safety study (N = 500, NCT02203838) was conducted with participants receiving 120 mg of extended-release risperidone for up to 13 months noting a favorable safety profile with both studies leading to FDA approval (see PERSERISUS package insert [USPI]). The original analyses of the double-blind study, published before the FDA review of the New Drug Application, evaluated changes from baseline scores across all visits (day 15, 29, 43, and 57) on the Positive and Negative Syndrome Scale (PANSS) total score (primary end point), subscores (exploratory end points), and the Clinical Global Impression– Severity of Illness (CGI-S) scale (secondary end point) using a mixed-effects model for repeated measures for extended-release risperidone 90 and 120 mg compared with placebo. Final assessment scores for those who terminated the study early were carried forward to the end of the study (day 57) before the mixed-effects model for repeated measure analysis was performed. The FDA requested a revised analysis of the efficacy end points where the results of the last assessment were not carried forward to day 57 and early termination assessments that were collected during an unscheduled visit were excluded. In addition, the statistical inferences for the primary and secondary end point analyses were conducted on the change from baseline to day 57 to better reflect the objectives stated in the protocol. Lastly, the FDA requested unadjusted 95% confidence intervals (CIs) for the USPI. This Letter to the Editors discusses the revised analysis because it is thought to provide a more reliable evaluation of treatment effects and explains the differences between the results presented in the original publication and those in the USPI. Men and women aged 18 to 55 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia and acute exacerbation of schizophrenia within 8 weeks of screening who were likely to benefit from psychiatric hospitalization or continued hospitalization were enrolled and randomized to receive 2 monthly subcutaneous injections of extended-release risperidone (90 or 120 mg) or placebo. Additional entry criteria included PANSS total score of 80 to 120 at screening and a score greater than 4 on at least 2 of the following PANSS Positive Symptoms subscale items: hallucinatory behavior, delusions, conceptual disorganization, or suspiciousness/persecution. Revised analyses were performed with the original analysis population, which comprised all randomized subjects who received at least 1 dose of extended-release risperidone or placebo and had data recorded for at least 1 postbaseline PANSS total score, and used the original adjustments for multiplicity (the significance level for the PANSS total score and subscores was determined by Dunett procedure controlling for PANSS total score and subscores for a 2-sided 0.05 type 1 error). A total of 111 and 114 subjects were in the extended-release risperidone 90and 120-mg groups, respectively, and 112 subjects were in the placebo group; early termination assessments from unscheduled visits in 26 (23.2%), 19 (17.1%), and 27 (23.1%) patients in the placebo, 90-mg, and 120-mg groups, respectively, were removed from the analyses. Two assessments at planned scheduled visits in each group were not carried forward at day 57. In the revised analyses, the improvements in PANSS total score and in CGI-S score at day 57 (primary and secondary end points) were significantly greater for both extended-release risperidone doses than placebo. The least-squares (LS) mean change (SE) from baseline to day 57 in the PANSS total score for placebo was −13.4 (1.6), whereas the LS mean change for extended-release risperidone 90 and 120mgwas −19.9 (1.6) and−23.6 (1.6), respectively. The LSmean change from baseline differences between each active treatment and placebo (95% adjusted and unadjusted CIs) were −6.5 (adjusted = −11.4 to −1.6, unadjusted = −10.9 to −2.1) and −10.2 (adjusted = −15.2 to −5.3, unadjusted = −14.6 to −5.9) with P values of 0.007 and less than 0.0001 for 90 and 120 mg, respectively. These significant improvements were observed as early as day 15 (first assessment) and at each subsequent time point (Fig. 1). The LS mean (SE) change from baseline to day 57 in the CGI-S score for extended-release risperidone 90 and 120 mg was −1.12 (0.09) and −1.35 (0.09), respectively, whereas the LSmean change for placebo was −0.81 (0.09). The LS mean change from baseline differences between each active dose and placebowere −0.35 (adjusted = −0.64 to −0.07, unadjusted = −0.61 to −0.10) and −0.58 (adjusted = −0.87 to −0.29, unadjusted = −0.83 to −0.32) with an adjusted P values of 0.0115 and less than 0.0001 for 90 and 120 mg, respectively. Both extended-release risperidone 90 and 120 mg had a statistically significantly larger mean decrease (improvement) from baseline in PANSS Positive Symptoms subscale score (adjusted P = 0.0019 and P < 0.0001, unadjusted 95% CI = −3.8 to −1.0 and −4.8 to −2.0 for 90 and 120 mg, respectively) and PANSS General Psychopathology subscale score (adjusted P = 0.0015 and P < 0.0001, unadjusted 95% CI = −6.1 to −1.6 and −7.7 to −3.2 for 90 and 120 mg, respectively) compared with placebo at day 57. The revised analysis detected a significant improvement in the PANSS Negative Symptoms subscale score with 120 mg compared with placebo (adjusted P = 0.0458, LS mean = −1.4, unadjusted 95% CI = −2.6 to −0.2). A numerical nonsignificant improvement was observed with 90 mg. This revised analysis, in which only data collected at planned scheduled assessment points were included andmissing data were not imputed, confirms the original conclusion that extended-release risperidone 90 and 120 mg are effective for the treatment of acute schizophrenia in adults. The results from this more sensitive analysis were similar to the original analysis for both the PANSS total score and CGI-S score as well as the Positive Symptoms and General Psychopathology subscale scores. However, in the revised analysis, extended-release risperidone 120 mg (P < 0.05), but not 90 mg, was statistically superior to placebo for the PANSS Negative Symptoms subscale; no such differencewas observed in the original analysis. The revised statistical approach gives an accurate evaluation of the effects of this extended-release risperidone formulation in patients who remain in care because those who withdrew from the study were no longer considered as completers. The main advantages of this long-acting injectable LETTERS TO THE EDITORS

Objective: Deficits in cognitive empathy are well-documented in individuals with schizophrenia and are related to reduced community functioning. The temporoparietal junction (TPJ) is closely linked to cognitive empathy. We compared the relationship between baseline cognitive empathy and changes in TPJ thickness over 24 months between individuals with schizophrenia and healthy controls. Methods: Individuals with schizophrenia ( n = 29) and healthy controls ( n = 26) completed a cognitive empathy task and underwent structural neuroimaging at baseline and approximately 24 months later. Symmetrized percent change scores were calculated for right and left TPJ, as well as whole-brain volume, and compared between groups. Task accuracy was examined as a predictor of percent change in TPJ thickness and whole-brain volume in each group. Results: Individuals with schizophrenia demonstrated poorer accuracy on the cognitive empathy task ( p < 0.001) and thinner TPJ cortex relative to controls at both time points ( p = 0.01). In schizophrenia, greater task accuracy was uniquely related to less thinning of the TPJ over time ( p = 0.02); task accuracy did not explain changes in left TPJ or whole-brain volume. Among controls, task accuracy did not explain changes in right or left TPJ, or whole-brain volume. Conclusions: Our findings suggest that greater cognitive empathy may explain sustained integrity of the right TPJ in individuals with schizophrenia, suggesting a contributory substrate for the long-term maintenance of this process in psychosis. Cognitive empathy was not related to changes in whole-brain volume, demonstrating the unique role of the TPJ in cognitive empathy.

Background: Positive and Negative Syndrome Scale (PANSS) data from a pivotal phase 3 study in participants with schizophrenia of RBP-7000, a recently marketed long-acting subcutaneous injectable risperidone formulation, were examined to determine if dose-response relationships existed for different items of the PANSS.Methods: Changes in the 30 PANSS items were analyzed individually and using the 5 factor-analysis-derived dimensions defined by Marder and colleagues. Subgroups of patients who could benefit from the RBP-7000 120 mg dose were investigated.Results: 337 participants were randomized and received study medication (RBP-7000 90 mg n = 111, RBP-7000 120 mg n = 114, placebo n = 112). Dose-dependent responses were observed in items from the study-specified PANSS positive and general psychopathology exploratory subscales. Dose-dependent responses were observed across all 5 Marder dimensions, with the largest effect sizes observed with the 120 mg dose in the uncontrolled hostility/excitement (UHE) and anxiety/depression dimensions. Participants with baseline UHE dimension scores ≥ 9 demonstrated greater improvement in PANSS total score at the 120 mg dose compared to the 90 mg dose.Conclusions: RBP-7000 demonstrated efficacy across both the primary and exploratory PANSS study endpoints and the post hoc Marder dimensions. Schizophrenia patients with higher baseline Marder UHE scores may benefit from initiation of treatment at the 120 mg dose.Trial Registration: ClinicalTrials.gov identifier: NCT02109562.

This chapter outlines the evolution of psychiatric understanding of mental disorders utilizing seven landmark texts that have informed current nosology. Important themes reviewed in this chapter include the foundational distinction between dementia praecox and manic-depressive insanity (Emil Kraepelin), drastic diagnostic differences between American and British psychiatrists reported in the 1970s (the US–UK diagnostic project), development of operationalized diagnostic criteria (Feighner criteria), the biopsychosocial model (George Engel), the philosophical account of mental disorder as harmful dysfunction (Jerome Wakefield), the endophenotype concept (Irving Gottesman and Todd Gould), and the Research Domain Criteria (RDoC) by the National Institute of Mental Health. Historical and theoretical links between these different texts and thinkers are highlighted and are offered to the reader in an integrated narrative of psychiatry’s conceptual development.

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11–20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

RBP-7000 (PERSERIS™), a once-monthly subcutaneous extended-release risperidone formulation approved for the treatment of schizophrenia in adults, was designed to deliver clinically relevant plasma concentrations on the first day of dosing (with no loading or supplemental dosing required) and throughout the 1-month dosing interval. The efficacy of RBP-7000 was established in an 8-week, double-blind, placebo-controlled trial in which significant improvements were observed in Positive and Negative Syndrome Scale (PANSS) total and subscale scores. This post hoc analysis examined the effects of RBP-7000 on the individual items that comprise the PANSS Positive, Negative, and General Psychopathology subscales. In the 8-week, multicenter, Phase III, double-blind, placebo-controlled, inpatient study (NCT02109562), adults 18–55 years with acute schizophrenia were randomized to monthly injections of placebo (N=112), RBP-7000 90 mg (N=111) or RBP-7000 120 mg (114). Eligible participants were required to have a PANSS total score 80–120 (inclusive) at screening and a score of ≥4 on at least 2 of the following PANSS Positive subscale items: hallucinatory behavior, delusions, conceptual disorganization, suspiciousness/persecution. In a post hoc analysis of this ITT population, a mixed-effects model for repeated measures with no multiplicity adjustments, was used to examine observed changes in the scores of the 30 individual PANSS items from baseline at day 57. Compared with placebo, treatment with either 90 mg or 120 mg RBP-7000 improved 4 out of 7 PANSS Positive items: hallucinatory behavior (90 mg; 120 mg, P<0.001), conceptual disorganization (90 mg; 120 mg, P<0.01), delusions (90 mg; 120 mg, P<0.05), and suspiciousness/persecution (90 mg; 120 mg, P<0.05). Additionally, improvements in hostility (P<0.01) and excitement scores were observed with RBP-7000 120 mg vs placebo (P<0.01). Treatment with RBP-7000 120 mg also improved 2 PANSS Negative item scores (emotional withdrawal [P<0.01] and passive/apathetic withdrawal [P<0.05]), while stereotyped thinking (P=0.054) and difficulty in abstract thinking (P=0.07) trended toward improvement. Both RBP-7000 doses improved 6 of 16 PANSS General Psychopathology item scores vs placebo: depression (90 mg; 120 mg, P<0.001), active social avoidance (90 mg, 120 mg, P<0.05), uncooperativeness (90 mg, 120 mg, P<0.05), poor attention (90 mg, 120 mg, P<0.05), anxiety (90 mg, 120 mg, P<0.05), and tension (90 mg, 120 mg, P<0.05). Improvements in poor impulse control (P<0.001) and somatic concern (P<0.05) were also observed with RBP-7000 120 mg, while the 90 mg dose improved motor retardation (P<0.01). Treatment with both 90 mg and 120 mg of RBP-7000 improved the majority of PANSS items. Importantly, treatment with the higher 120 mg dose resulted in improvement on 2 PANSS Negative items, suggesting RBP-7000 may be useful in addressing difficult to treat negative symptoms.

A member of the Herpesviridae group of viruses, cytomegalovirus (CMV) has a seroprevalence of approximately 58% in the United States, although the seroprevalence varies by age and other sociodemographic factors. While prenatal infection with CMV has been associated with adverse effects on neurodevelopment, growing evidence suggests it may also be associated with alterations in cognition in adults. In addition, CMV seropositivity has been linked to several psychiatric conditions, including schizophrenia. While previous work has found CMV seropositivity associations with cognition in schizophrenia, little work has investigated its specific impact on underlying brain integrity in the illness. The overarching aim of this project was to examine the influence of CMV status on cortical integrity and behavioral functioning in samples of schizophrenia and healthy individuals both seropositive and negative for the virus. Schizophrenia (SCZ = 63; 31 CMV+) and healthy control volunteers (CON = 25; 12 CMV+) with clinical, cognitive, and imaging data and available blood samples were used for the study. CMV seropositivity was established with micro-enzyme-linked immunosorbent assay (ELISA) analysis using a commercially available research kit for quantitative immunoenzymatic determination of anti-CMV IgG-class antibodies. Cognitive and clinical functioning was assessed using a standardized battery. Structural T1-weighted images were processed using the FreeSurfer toolkit v5.3.0. Analyses included ANOVA models examining differences in cortical thickness and cognition between CMV seropositive (+) and negative (-) groups per condition (SCZ and CON), within-group linear models examining the relationship between anti-CMV IgG antibody titer values and cortical thickness, and Pearson correlation models between cortical ROIs thickness and behavioral variables in SCZ. No significant cortical thickness differences were observed in SCZ(+) vs SCZ(-), as well as in CON(+) vs CON(-) contrast maps; however, linear modeling of IgG antibody titer values along the cortical surface revealed patterns similar to the (+/-) contrasts for each group. This included in CON = sensorimotor regions, supramarginal gyrus, insula, and medial occipital regions and in SCZ = posterior cingulate, frontal pole, and parietal association regions that survived multiple comparison correction and subsequently utilized as volumetric ROIs in Pearson models. Correlations revealed significant relationships between parietal association cortex with verbal intellect (r=0.41, p=0.003) and negative symptoms (r=-0.32, p=0.023); and posterior cingulate with disorganization (r=0.40, p=0.004) while controlling for the effects of age in all models. Contrast results revealed attenuated, but differential, patterns of cortical loss in CMV(+) subjects for each group that were supported by linear modeling of IgG antibody titer values. Most striking were abnormalities in posterior cingulate and parietal association regions in SCZ that also related to aspects of IQ and clinical symptomatology. Overall, findings suggest the effects of the CMV pathogen have a unique neurobiological expression in SCZ that may explain some features of its behavioral profile.

Objective: The authors sought to develop and validate a suite of dimensional measures of psychiatric syndromes for use in a criminal justice population. Methods: The previously validated Computerized Adaptive Test-Mental Health (CAT-MH) was administered to a sample of 475 defendants in the Cook County Bond Court. Item-level data were used to determine which test items exhibited differential item functioning in this population compared with the population used for the original calibration. Results: After removal of nine items that exhibited differential item functioning from the CAT-MH, correlations between scores based on the original calibration from a nonjustice-involved population and the newly computed scores based on a sample of bond court defendants showed a correlation coefficient of r=0.96 to r=0.99. Conclusions: With a slight modification of the original CAT-MH, the tool was successfully used to measure severity of depression, anxiety, mania and/or hypomania, suicidality, and substance use disorder in an English- and Spanish-speaking criminal justice population.