Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition.

BACKGROUND: Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with 'background connectivity' following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders. Thus, here we examine background connectivity during executive processing in a cohort of participants with first-episode psychosis (FEP). METHODS: The following fMRI study examined background connectivity of the dorsolateral prefrontal cortex (DLPFC), during working memory engagement in a group of 43 patients with FEP, relative to 35 healthy controls (HC). Findings were also examined in relation to measures of executive function. RESULTS: The FEP group relative to HC showed significantly lower background DLPFC connectivity with bilateral superior parietal lobule (SPL) and left inferior parietal lobule. Background connectivity between DLPFC and SPL was also positively associated with overall cognition across all subjects and in our FEP group. In comparison, resting-state frontoparietal connectivity did not differ between groups and was not significantly associated with overall cognition, suggesting that psychosis-related alterations in executive networks only emerged during states of goal-oriented behavior. CONCLUSIONS: These results provide novel evidence indicating while frontoparietal connectivity at rest appears intact in psychosis, when engaged during a cognitive state, it is impaired possibly undermining cognitive control capacities in FEP.

Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial.

Importance: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. Objective: To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. Interventions: Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). Main Outcomes and Measures: The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. Results: Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45). Conclusions and Relevance: Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission. Trial Registration: ClinicalTrials.gov Identifier: NCT03170362.

Changing the Paradigm of Craniofacial Reconstruction: A Prospective Clinical Trial of Autologous Fat Transfer for Craniofacial Deformities.

OBJECTIVE: This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options. BACKGROUND: Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities. METHODS: In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9 ±â€Š13.2 mL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment. RESULTS: No serious adverse events occurred. Volume retention averaged 63 ±â€Š17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996, P < 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P = 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%, P = 0.009). Satisfaction with physical appearance (P = 0.002), social relationships (P = 0.02), and social functioning quality of life (P = 0.05) improved from baseline to 9 months. CONCLUSIONS: For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.

Key Variables for Effective eHealth Designs for Individuals With and Without Mental Health Disorders: 212-4 Fractional Factorial Experiment.

BACKGROUND: eHealth applications not only offer the potential to increase service convenience and responsiveness but also expand the ability to tailor services to improve relevance, engagement, and use. To achieve these goals, it is critical that the designs are intuitive. Limited research exists on designs that work for those with a severe mental illness (SMI), many of whom have difficulty traveling for treatments, reject or infrequently seek treatment, and tend to discontinue treatments for significant periods. OBJECTIVE: This study aims to evaluate the influence of 12 design variables (eg, navigational depth, reading level, and use of navigational lists) on the usability of eHealth application websites for those with and without SMI. METHODS: A 212-4 fractional factorial experiment was used to specify the designs of 256 eHealth websites. This approach systematically varied the 12 design variables. The final destination contents of all websites were identical, and only the designs of the navigational pages varied. The 12 design elements were manipulated systematically to allow the assessment of combinations of design elements rather than only one element at a time. Of the 256 websites, participants (n=222) sought the same information on 8 randomly selected websites. Mixed effect regressions, which accounted for the dependency of the 8 observations within participants, were used to test for main effects and interactions on the ability and time to find information. Classification and regression tree analyses were used to identify effects among the 12 variables on participants' abilities to locate information, for the sample overall and each of the 3 diagnostic groups of participants (schizophrenia spectrum disorder [SSD], other mental illnesses, and no mental illness). RESULTS: The best and worst designs were identified for each of these 4 groups. The depth of a website's navigation, that is, the number of screens users needed to navigate to find the desired content, had the greatest influence on usability (ability to find information) and efficiency (time to find information). The worst performing designs for those with SSD had a 9% success rate, and the best had a 51% success rate: the navigational designs made a 42% difference in usability. For the group with other mental illnesses, the design made a 50% difference, and for those with no mental illness, a 55% difference was observed. The designs with the highest usability had several key design similarities, as did those with the poorest usability. CONCLUSIONS: It is possible to identify evidence-based strategies for designing eHealth applications that result in significantly better performance. These improvements in design benefit all users. For those with SSD or other SMIs, there are designs that are highly effective. Both the best and worst designs have key similarities but vary in some characteristics.

Correction: Key Variables for Effective eHealth Designs for Individuals With and Without Mental Health Disorders: 212-4 Fractional Factorial Experiment.

[This corrects the article DOI: 10.2196/23137.].

Adjunctive yoga training for persons with schizophrenia: who benefits?

OBJECTIVE: The aim of this study was to identify factors associated with acceptability and efficacy of yoga training (YT) for improving cognitive dysfunction in individuals with schizophrenia (SZ). METHODS: We analysed data from two published clinical trials of YT for cognitive dysfunction among Indians with SZ: (1) a 21-day randomised controlled trial (RCT, N = 286), 3 and 6 months follow-up and (2) a 21-day open trial (n = 62). Multivariate analyses were conducted to examine the association of baseline characteristics (age, sex, socio-economic status, educational status, duration, and severity of illness) with improvement in cognition (i.e. attention and face memory) following YT. Factors associated with acceptability were identified by comparing baseline demographic variables between screened and enrolled participants as well as completers versus non-completers. RESULTS: Enrolled participants were younger than screened persons who declined participation (t = 2.952, p = 0.003). No other characteristics were associated with study enrollment or completion. Regarding efficacy, schooling duration was nominally associated with greater and sustained cognitive improvement on a measure of facial memory. No other baseline characteristics were associated with efficacy of YT in the open trial, the RCT, or the combined samples (n = 148). CONCLUSIONS: YT is acceptable even among younger individuals with SZ. It also enhances specific cognitive functions, regardless of individual differences in selected psychosocial characteristics. Thus, yoga could be incorporated as adjunctive therapy for patients with SZ. Importantly, our results suggest cognitive dysfunction is remediable in persons with SZ across the age spectrum.

Religious Community Partnerships: a Novel Approach to Teaching Psychiatry Residents about Religious and Cultural Factors in the Mental Health Care of African-Americans.

OBJECTIVE: Promoting awareness in residency training about the influence of religion on the doctor's and patient's ability to negotiate a patient-centered treatment plan is challenging and yet important for improving the quality of mental health care for religious individuals. This paper aims to explore the use of community partners and non-psychiatry faculty to provide this education within psychiatry residency programs. METHODS: Fifty-one psychiatry residents at an academic psychiatric hospital took part in a 4-h interdisciplinary workshop aimed at improving doctors' overall approach to treating African-American Christian patients. Community-based African-American clergy and mental health professionals, hospital-based psychiatrists, and primary care physicians facilitated educational sessions. A majority of the facilitators were African-American. A pre- and post-workshop survey was administered to measure change in participant attitudes and comfort levels associated with exposure to the workshop. Paired t tests on three subscales were used to calculate change in attitudes on pre- to post-workshop surveys. RESULTS: Resident scores on each of the three factor subscales increased significantly between pre- and post-workshop assessments: comfort in discussions with patients about spirituality [t [17] = 2.758; p = 0.013]; willingness to collaborate with clergy [t [16] = 3.776; p = 0.002]; and importance of religion to mental health [t [17] = 3.645; p = 0.002]. CONCLUSION: Findings suggest that collaboration between academic and community-based clergy, physicians, and other mental health providers may be a feasible method of improving psychiatry trainees' comfort in addressing religion in psychiatric care to ultimately provide more culturally competent care.

The Role of Primary Care Experiences in Obtaining Treatment for Depression.

BACKGROUND: Managing depression in primary care settings has increased with the rise of integrated models of care, such as patient-centered medical homes (PCMHs). The relationship between patient experience in PCMH settings and receipt of depression treatment is unknown. OBJECTIVE: In a large sample of Veterans diagnosed with depression, we examined whether positive PCMH experiences predicted subsequent initiation or continuation of treatment for depression. DESIGN AND PARTICIPANTS: We conducted a lagged cross-sectional study of depression treatment among Veterans with depression diagnoses (n = 27,362) in the years before (Y1) and after (Y2) they completed the Veterans Health Administration's national 2013 PCMH Survey of Healthcare Experiences of Patients. MAIN MEASURES: We assessed patient experiences in four domains, each categorized as positive/moderate/negative. Depression treatment, determined from administrative records, was defined annually as 90 days of antidepressant medications or six psychotherapy visits. Multivariable logistic regressions measured associations between PCMH experiences and receipt of depression treatment in Y2, accounting for treatment in Y1. KEY RESULTS: Among those who did not receive depression treatment in Y1 (n = 4613), positive experiences in three domains (comprehensiveness, shared decision-making, self-management support) predicted greater initiation of treatment in Y2. Among those who received depression treatment in Y1 (n = 22,749), positive or moderate experiences in four domains (comprehensiveness, care coordination, medication decision-making, self-management support) predicted greater continuation of treatment in Y2. CONCLUSIONS: In a national PCMH setting, patient experiences with integrated care, including care coordination, comprehensiveness, involvement in shared decision-making, and self-management support predicted patients' subsequent initiation and continuation of depression treatment over time-a relationship that could affect physical and mental health outcomes.

Emotion recognition and social skills in child and adolescent offspring of parents with schizophrenia.

INTRODUCTION: Emotion recognition, a social cognition domain, is impaired in people with schizophrenia and contributes to social dysfunction. Whether impaired emotion recognition emerges as a manifestation of illness or predates symptoms is unclear. Findings from studies of emotion recognition impairments in first-degree relatives of people with schizophrenia are mixed and, to our knowledge, no studies have investigated the link between emotion recognition and social functioning in that population. METHODS: This study examined facial affect recognition and social skills in 16 offspring of parents with schizophrenia (familial high-risk/FHR) compared to 34 age- and sex-matched healthy controls (HC), ages 7-19. RESULTS: As hypothesised, FHR children exhibited impaired overall accuracy, accuracy in identifying fearful faces, and overall recognition speed relative to controls. Age-adjusted facial affect recognition accuracy scores predicted parent's overall rating of their child's social skills for both groups. CONCLUSIONS: This study supports the presence of facial affect recognition deficits in FHR children. Importantly, as the first known study to suggest the presence of these deficits in young, asymptomatic FHR children, it extends findings to a developmental stage predating symptoms. Further, findings point to a relationship between early emotion recognition and social skills. Improved characterisation of deficits in FHR children could inform early intervention.

Racial/Ethnic Differences in Primary Care Experiences in Patient-Centered Medical Homes among Veterans with Mental Health and Substance Use Disorders.

BACKGROUND: Patient-Centered Medical Homes (PCMH) may be effective in managing care for racial/ethnic minorities with mental health and/or substance use disorders (MHSUDs). How such patients experience care in PCMH settings is relatively unknown. OBJECTIVE: We aimed to examine racial/ethnic differences in experiences with primary care in PCMH settings among Veterans with MHSUDs. DESIGN: We used multinomial regression methods to estimate racial/ethnic differences in PCMH experiences reported on a 2013 national survey of Veterans Affairs patients. PARTICPANTS: Veterans with past-year MHSUD diagnoses (n = 65,930; 67 % White, 20 % Black, 11 % Hispanic, 1 % American Indian/Alaska Native[AI/AN], and 1 % Asian/Pacific Island[A/PI]). MAIN MEASURES: Positive and negative experiences from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) PCMH Survey. RESULTS: Veterans with MHSUDs reported the lowest frequency of positive experiences with access (22 %) and the highest frequency of negative experiences with self-management support (30 %) and comprehensiveness (16 %). Racial/ethnic differences (as compared to Whites) were observed in all seven healthcare domains (p values < 0.05). With access, Blacks and Hispanics reported more negative (Risk Differences [RDs] = 2 .0;3.6) and fewer positive (RDs = -2 .3;-2.3) experiences, while AI/ANs reported more negative experiences (RD = 5.7). In communication, Blacks reported fewer negative experiences (RD = -1.3); AI/ANs reported more negative (RD = 3.6) experiences; and AI/ANs and APIs reported fewer positive (RD = -6.5, -6.7) experiences. With office staff, Hispanics reported fewer positive experiences (RDs = -3.0); AI/ANs and A/PIs reported more negative experiences (RDs = 3.4; 3.7). For comprehensiveness, Blacks reported more positive experiences (RD = 3.6), and Hispanics reported more negative experiences (RD = 2.7). Both Blacks and Hispanics reported more positive (RDs = 2.3; 4.2) and fewer negative (RDs = -1.8; -1.9) provider ratings, and more positive experiences with decision making (RDs = 2.4; 3.0). Blacks reported more positive (RD = 3.9) and fewer negative (RD = -5.1) experiences with self-management support. CONCLUSIONS: In a national sample of Veterans with MHSUDs, potential deficiencies were observed in access, self-management support, and comprehensiveness. Racial/ethnic minorities reported worse experiences than Whites with access, comprehensiveness, communication, and office staff helpfulness/courtesy.

Insight and neurocognitive functioning in bipolar subjects.

BACKGROUND: Insight concerning having a mental illness has been found to influence outcome and effectiveness of treatment. It has been studied mainly in the area of schizophrenia with few studies addressing other disorders. This study evaluates insight in individuals with bipolar disorder using the Scale to Assess Unawareness of Mental Disorder (SUMD), a comprehensive interview for evaluation of awareness of illness and attribution of symptoms. The hypothesis was that in bipolar disorder level of awareness may be associated with numerous factors including neurocognitive function, structural changes in the frontal lobes and hippocampus evaluated by MRI, neurocognitive status, severity of mania and other psychiatric symptoms and comorbid alcoholism. METHOD: In order to evaluate this hypothesis 33 individuals with DSM-IV diagnosed bipolar disorder, some with and some without comorbid alcoholism, were administered the SUMD and a number of other procedures including a quantitative MRI measuring volume of the frontal lobes and hippocampus, a brief battery of neurocognitive tests, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. The data were analyzed by comparing participants with and without alcoholism on these procedures using t tests and by linear multiple regression, with SUMD ratings of awareness and attribution as the dependent variables and variable sets from the other procedures administered as multivariate independent variables. RESULTS: The median score obtained from the SUMD for current awareness was in a range between full awareness and uncertainty concerning presence of a mental disorder. For attribution, the median score indicated that attribution was usually made to the illness itself. None of the differences between participants with and without comorbid alcoholism were significant for the SUMD awareness and attribution scores, neurocognitive or MRI variables. The multiple regression analyses only showed a significant degree of association between the SUMD awareness score and the Young Mania Rating Scale (r(2)=.632, p<.05). A stepwise analysis indicated that items assessing degree of insight, irritability, and sleep disturbance met criteria for entry into the regression equation. None of the regression analyses for the SUMD attribution item were significant. CONCLUSIONS: Apparently unlike the case for schizophrenia, most of the participants, all of whom had bipolar disorder, were aware of their symptoms and correctly related them to a mental disorder. Hypotheses concerning the relationships between degree of unawareness and possible contributors to its development including comorbid alcoholism, cognitive dysfunction and structural reduction of gray matter in the frontal region and hippocampus, were not associated with degree of unawareness but symptoms of mania were significantly associated. The apparent reason for this result is that the sample obtained a SUMD modal awareness score of 1 or 2, reflecting the area between full awareness and uncertainty about having a mental disorder. None of the participants were rated as having a 5 response reflecting the belief that s/he does not have a mental disorder.

Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data.

STUDY OBJECTIVES: This study aimed to estimate the 12-month prevalence of diagnosed sleep disorders among veterans with and without serious mental illnesses (SMI) in Veterans Affairs health record data in 2019. We also examined diagnosed sleep disorders across a 9-year period and explored associations with demographic and health factors. METHODS: This study used health record data from VISN 4 of the Veterans Health Administration from 2011 to 2019. SMI diagnoses included schizophrenia and bipolar spectrum diagnoses as well as major depression with psychosis. Sleep diagnoses included insomnias, hypersomnias, sleep-related breathing disorders, circadian rhythm sleep-wake disorders, and sleep-related movement disorders. Demographic and health-related factors were also collected from the record. RESULTS: In 2019, 21.8% of veterans with SMI were diagnosed with a sleep disorder. This is a significantly higher proportion than for veterans without SMI, 15.1% of whom were diagnosed with a sleep disorder. Sleep disorder rates were highest in veterans with a chart diagnosis of major depression with psychosis. From 2011 to 2019, the overall prevalence of sleep disorders in veterans with SMI more than doubled (10.2%-21.8%), suggesting improvements in the detection and diagnosis of sleep concerns for this group. CONCLUSIONS: Our findings suggest that identification and diagnosis of sleep disorders for veterans with SMI has improved over the past decade, though diagnoses still likely underrepresent actual prevalence of clinically relevant sleep concerns. Sleep concerns may be at particularly high risk of going untreated in veterans with schizophrenia-spectrum disorders. CITATION: Bonfils KA, Longenecker JM, Soreca I, et al. Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data. J Clin Sleep Med. 2023;19(9):1651-1660.

Stem Cell Therapy Enriched Fat Grafting for the Reconstruction of Craniofacial Deficits.

Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting. Methods: Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months. Results: All patients had improvement in appearance. There were no serious adverse events. There was no significant difference in volume retention between the SVF-enriched and control regions overall (50.3% versus 57.3%, P = 0.269) or comparing malar regions (51.4% versus 56.7%, P = 0.494). Patient age, smoking status, obesity, and diagnosis of diabetes did not impact volume retention. Cell viability was 77.4% ± 7.3%. Cellular subpopulations were 60.1% ± 11.2% adipose derived stem cells, 12.2 ± 7.0% endothelial cells, and 9.2% ± 4.4% pericytes. A strong positive correlation was found between CD146+ CD31-pericytes and volume retention (R = 0.863, P = 0.027). Conclusions: Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.

Hierarchical Symptom Components in Early Psychosis.

BACKGROUND AND HYPOTHESIS: Quantitative models of psychopathology can empirically guide subclassification of heterogeneous clinical presentations such as psychosis; they are particularly well-equipped to capture the nuanced symptomatology observed in first-episode psychosis. As well, components may be better aligned with biological variables. The current study sought to confirm and extend knowledge of the hierarchical structure of psychosis symptoms in first-episode psychosis. Based on past hierarchical work, we hypothesized that a 4 component level would be most closely associated with longitudinal disability. STUDY DESIGN: Participants with early-stage psychosis (N = 370) underwent clinical assessment with the scale for the assessment of positive symptoms (SAPS), scale for assessment of negative symptoms (SANS), and global assessment scale(GAS). A subset was assessed at 6 months (N = 221) and 1 year (N = 207). Hierarchical symptom components were extracted at 12 levels. The predictive utility of the components for global functioning was tested. STUDY RESULTS: As predicted, the 4-component model (reality distortion, thought disorder, inexpressivity, apathy/asociality) provided a superior prediction of functioning over other levels of the hierarchy. Baseline apathy/asociality longitudinally predicted functioning beyond the shared variance of the components at 6 months (b = -4.83, t(216) = -5.37, p < .001, R2adj = 0.12) and 1-year (b = -4.49, t(202) = -4.38, p < .001, R2adj = 0.09). CONCLUSIONS: The hierarchical structure of psychotic symptomatology and its external validity have been robustly established in independent, longitudinal first-episode psychosis samples. The established model incorporates multiple levels of granularity that can be flexibly applied based on the level that offers the greatest predictive utility for external validators.

Premorbid adjustment in childhood is associated with later emotion management in first-episode schizophrenia.

Poor premorbid adjustment and social functioning deficits are recognized as cardinal features of schizophrenia. Whether premorbid maladjustment is associated with interpersonal functioning problems that manifest during the first episode of psychosis is less well-established. No previous work has investigated the relationship between premorbid adjustment and a key component of social cognition (emotion management) during the early phase of schizophrenia. A sample of 119 individuals (40 experiencing a first episode of schizophrenia, FE-SZ, 22 experiencing a first episode of another psychotic disorder, FE-OP, and 57 healthy controls, HC) participated in an assessment of premorbid adjustment and emotion management, measured using the Cannon-Spoor Premorbid Adjustment Scale (PAS) and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) Managing Emotions (ME) scale. The relationship between premorbid adjustment (from age 5 to onset of psychotic symptoms) and ME was examined, as well as the specific relationship between childhood premorbid adjustment (ages 5-11) and ME. Results indicated that both FE-SZ and FE-OP participants exhibited significantly worse premorbid adjustment (all p's < 0.01) across development and lower ME scores when compared to HC participants. Among FE-SZ participants only, premorbid maladjustment in childhood was correlated with deficits in emotion management. This study is the first to suggest that poor premorbid social and academic functioning in childhood is related to later deficits in emotion management in those experiencing a first episode of schizophrenia. These results point to a possible relationship between early developmental deficits in premorbid social and school functioning and social cognitive deficits during the early (first episode) phase of schizophrenia.

Functional outcomes from psychotherapy for people with posttraumatic stress disorder: A meta-analysis.

People with posttraumatic stress disorder (PTSD) experience a wide array of symptoms, often accompanied by significant functional and quality of life impairments. Evidence-based psychotherapies are effective for alleviating symptoms in this group, but functional outcomes following psychotherapy are understudied. This study aimed to synthesize existing work on functional outcomes of psychotherapy to conduct a meta-analytic investigation examining whether people with PTSD experience significant improvements in functioning and quality of life following a course of psychotherapy. A literature search was conducted for studies reporting results of randomized clinical trials of psychotherapies for people diagnosed with PTSD that included a functional or quality of life outcome measured at pre- and post-intervention. Both between-groups and within-groups analyses were conducted using a random effects model. Fifty-six independent samples were included. Results suggest that, on average, people with PTSD experience significant, moderate improvement in functional outcomes after a course of psychotherapy. Taken together, this meta-analysis represents a substantial advance in our understanding of functional outcomes of psychotherapy for people with PTSD. Findings suggest that psychotherapy is one vehicle through which functional outcomes may be improved for this group, though notably to a lesser degree than symptom improvement.

Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site.

OBJECTIVE: Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period. METHODS: Electronic health records were evaluated for 101 patients prescribed LAI-As. A subset of 13 patients also participated in an interview and rated subjective concerns about pandemic-related barriers to medication adherence. RESULTS: Pandemic-related barriers to LAI-A adherence and/or changes to LAI-A medications were documented in 33% of the patients. Within-subjects comparison of an adherence metric computed from electronic health record data further suggested a somewhat higher incidence of missed or delayed LAI-A doses during the pandemic compared with before the pandemic. In contrast, only 2 of the 13 patients interviewed anticipated that pandemic-related concerns would interfere with medication adherence. CONCLUSIONS: The results of this study suggest that LAI-A access and adherence can be disrupted by pandemics and other public health emergencies but this finding may not generalize to other sites. As patients may not foresee the potential for disruption, psychiatric service providers may need to assist in proactively problem-solving barriers to access. Improved preparedness and additional safeguards against pandemic-related disruptions to LAI-A access and adherence may help mitigate adverse outcomes in the future. Identifying patients at elevated risk for such disruptions may help support these efforts.

3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia.

One branch of the tryptophan catabolic cascade is the kynurenine pathway, which produces neurotoxic [3-hydroxykynurenine (3-OHKY), quinolinic acid] and neuroinhibitory (kynurenic acid) compounds. Kynurenic acid acts as a competitive antagonist at the glycine site of N-methyl-d-asparate receptors at high concentrations and as a non-competitive antagonist on the α7-nicotinic acetylcholine receptor at low concentrations. Kynurenine compounds also influence cognitive functions known to be disrupted in schizophrenia. Alterations in tryptophan metabolism are therefore of potential significance for the pathophysiology of this disorder. In this paper, tryptophan metabolites were measured from plasma using high-pressure liquid chromatography coupled with electrochemical coulometric array detection, and relationships were tested between these metabolic signatures and clinical symptoms for 25 first-episode neuroleptic-naive schizophrenia patients. Blood samples were collected and clinical and neurological symptoms were rated at baseline and again at 4 wk following initiation of treatment. Level of 3-OHKY and total clinical symptom scores were correlated when patients were unmedicated and neuroleptic-naive, and this relationship differed significantly from the correlation observed for patients 4 wk after beginning treatment. Baseline psychosis symptoms were predicted only by neurological symptoms. Moreover, baseline 3-OHKY predicted clinical change at 4 wk, with the lowest concentrations of 3-OHKY being associated with the greatest improvement in symptoms. Taken together, our findings suggest a neurotoxic product of tryptophan metabolism, 3-OHKY, predicts severity of clinical symptoms during the early phase of illness and before exposure to antipsychotic drugs. Baseline level of 3-OHKY may also predict the degree of clinical improvement following brief treatment with antipsychotics.

Factor structure and risk factors for the health status of homeless veterans.

Homeless veterans have numerous health problems that have been previously characterized as falling into four major subgroups; addiction, psychosis, vascular disorders, and generalized medical and psychiatric illness. Comorbid conditions are common, often involving a combination of psychiatric and medical disorders. Using data from the same survey of homeless veterans that was used to establish these subgroups with cluster analysis, the present study examined the structure of these subgroup patterns through the use of factor analysis. This analysis yielded a five factor solution. They were named "Cardiac", Mood, Stress, Addiction, and Psychosis factors. Factor scores were computed and an odds ratio analysis was accomplished to determine the association between obtaining a high score on a given factor with a number of sociodemographic and homelessness related variables. It was concluded that health status of homeless veterans is a complex condition, but has a clear latent structure demonstrated by factor analysis. Scoring high or low on a particular factor is associated with numerous historical and sociodemographic considerations, notably age, ethnicity, and employment status.

Suicidal ideation and aggression in childhood, genetic variation and young adult depression.

BACKGROUND: Suicidal thoughts and behaviors have been studied in association with a variety of risk factors. The aim of the present study was to determine if levels of child/adolescent aggression and/or variation in candidate genes previously associated with suicidal behaviors in adults would influence the presence of suicidal ideation in childhood/adolescence, and to determine if ideation was associated with young adult depression. METHODS: A longitudinal study of children, adolescents and young adults who were at high or low risk for alcohol and other substance use disorders by familial background were assessed. The Child Behavior Checklist (CBCL) aggression scale scores with derived subtypes (physical and relational) and genetic variation (ANKK1, DRD2, COMT, SLC6A4, HTR2C) were used as predictors of the presence and onset of suicidal ideation in childhood using survival analysis. Structural equation models (SEM) were fit to determine the relative importance of the predictors controlling for background variables. RESULTS: CBCL aggression was significantly associated with child/adolescent suicidal ideation. One SNP in the ANKK1 gene (rs1800497), one in the HTR2C gene (rs6318), and two haplotypes, AAAC in the ANKK1-DRD2 complex and the CCC haplotype of the HTR2C gene, were significantly associated with the presence and onset of child/adolescent suicidal ideation. Follow up in young adulthood showed a significant relationship between suicidal ideation in childhood/adolescence and young adult depression. CONCLUSIONS: Genetic variation and presence of elevated aggression scores from the childhood CBCL are significant predictors of childhood suicidal ideation. Suicidal ideation in childhood and being female are predictors of young adult depression.