Physical Activity Can Enhance Life (PACE-Life): results from a 10-week walking intervention for individuals with schizophrenia spectrum disorders.

BACKGROUND: Premature mortality in individuals with schizophrenia spectrum disorders (SSDs) is largely due to high rates of chronic health conditions. Although exercise has been shown to improve health in this population, scalable and accessible interventions are limited. AIM: To examine the impact of Physical Activity Can Enhance Life (PACE-Life), a novel walking intervention, on physical activity, and on secondary outcomes of cardiorespiratory fitness (CRF), physical health, autonomous motivation, social support, and quality of life. METHOD: Sixteen individuals with SSDs were enrolled in a 10-week open trial. The intervention included walking groups, home-based walks, Fitbit use, and goal-setting and if-then plans. Within-group effect sizes were calculated to represent changes from baseline to post-test and 1-month follow-up. RESULTS: Participants increased self-reported weekly walking minutes and decreased daily hours spent sitting; however, Fitbit-recorded exercise behavior changed only minimally. There were also improvements in secondary outcomes including autonomous motivation and hip circumference. CRF improved only minimally, and findings were relatively unchanged with outliers removed from the full sample. CONCLUSIONS: This open trial demonstrates modest improvements in key parameters of exercise behavior and physical health from participating in PACE-Life. Future research should assess the efficacy of this intervention in a randomized controlled trial.

Community Mental Health Care Delivery During the COVID-19 Pandemic: Practical Strategies for Improving Care for People with Serious Mental Illness.

The COVID-19 pandemic has presented a formidable challenge to care continuity for community mental health clients with serious mental illness and for providers who have had to quickly pivot the modes of delivering critical services. Despite these challenges, many of the changes implemented during the pandemic can and should be maintained. These include offering a spectrum of options for remote and in-person care, greater integration of behavioral and physical healthcare, prevention of viral exposure, increased collaborative decision-making related to long-acting injectable and clozapine use, modifying safety plans and psychiatric advance directives to include new technologies and broader support systems, leveraging natural supports, and integration of digital health interventions. This paper represents the authors' collaborative attempt to both reflect the changes to clinical practice we have observed in CMHCs across the US during this pandemic and to suggest how these changes can align with best practices identified in the empirical literature.

Targeting reduced neural oscillations in patients with schizophrenia by transcranial alternating current stimulation.

Transcranial alternating current stimulation (tACS) modulates endogenous neural oscillations in healthy human participants by the application of a low-amplitude electrical current with a periodic stimulation waveform. Yet, it is unclear if tACS can modulate and restore neural oscillations that are reduced in patients with psychiatric illnesses such as schizophrenia. Here, we asked if tACS modulates network oscillations in schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast tACS with transcranial direct current stimulation (tDCS) and sham stimulation in 22 schizophrenia patients with auditory hallucinations. We used high-density electroencephalography to investigate if a five-day, twice-daily 10Hz-tACS protocol enhances alpha oscillations and modulates network dynamics that are reduced in schizophrenia. We found that 10Hz-tACS enhanced alpha oscillations and modulated functional connectivity in the alpha frequency band. In addition, 10Hz-tACS enhanced the 40Hz auditory steady-state response (ASSR), which is reduced in patients with schizophrenia. Importantly, clinical improvement of auditory hallucinations correlated with enhancement of alpha oscillations and the 40Hz-ASSR. Together, our findings suggest that tACS has potential as a network-level approach to modulate reduced neural oscillations related to clinical symptoms in patients with schizophrenia.

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia.

OBJECTIVE: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD). METHOD: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change. RESULTS: A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8). CONCLUSIONS: Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD. TRIAL REGISTRATION NUMBER: NCT02198794.

Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

The effect of intranasal oxytocin on neurocognition in people with schizophrenia: A randomized controlled trial.

Schizophrenia is characterized by persistent cognitive deficits that significantly impact functional outcomes. Despite the current available treatments, these deficits remain inadequately addressed, highlighting the need to explore the effect of more novel treatments on cognition. The current study examined the effect of intranasal oxytocin on cognitive functioning in people with schizophrenia by utilizing data from a 12-week, randomized controlled trial. Sixty-seven participants with schizophrenia or schizoaffective disorder were randomized to receive placebo or intranasal oxytocin. Participants completed a comprehensive neuropsychological battery at baseline and 12 weeks. The results demonstrated that intranasal oxytocin did not significantly improve cognition in people with schizophrenia compared to placebo. These findings suggest that oxytocin does not worsen or enhance cognition in people with schizophrenia. Yet, the current intervention did not standardize the timing of cognitive assessments relative to the timing of oxytocin administration, which may explain our findings. Future studies attempting to clarify this relationship would benefit from employing a more controlled approach to the timing of treatment and assessments.

Racial Disparities in Clozapine Prescription Patterns Among Patients With Schizophrenia.

OBJECTIVE: Previous research has suggested that demographic factors affect the likelihood of a patient with schizophrenia receiving a clozapine prescription. The authors aimed to determine the impact of race, social determinants of health, gender, rurality, and care patterns on clozapine prescription rates. METHODS: This cross-sectional observational study used structured electronic health records data from 3,160 adult patients diagnosed as having schizophrenia between October 1, 2015, and November 30, 2021, in a multifacility health system. The social vulnerability index (SVI) was used to quantify social determinants of health. Descriptive data analysis, logistic regression, and sensitivity analysis were conducted to identify differences between patients with schizophrenia who received a clozapine prescription and those who received antipsychotic medications other than clozapine. RESULTS: Overall, 401 patients with schizophrenia were given a clozapine prescription during the study period, and 2,456 received antipsychotics other than clozapine. Results of the logistic regression indicated that White race (OR=1.71, compared with Black race), community minority status and language SVI score (OR=2.97), and increased treatment duration (OR=1.36) were significantly associated with a higher likelihood of clozapine prescription; gender, rurality, age at first diagnosis, and ethnicity did not influence the likelihood of receiving clozapine. CONCLUSIONS: Black patients with schizophrenia had a lower likelihood of receiving a clozapine prescription compared with White patients, even after analyses accounted for demographic variables, social determinants of health, and care access patterns. Given the effectiveness of clozapine in managing treatment-resistant schizophrenia, it is crucial for future research to better understand the factors contributing to this treatment disparity.

Virtual Group-based Walking Intervention for Persons with Schizophrenia: A Pilot Randomized Controlled Trial.

Persons with schizophrenia have reduced cardiorespiratory fitness (CRF), a predictor of all-cause mortality. Exercise is effective for improving CRF; however, motivational challenges affecting those with schizophrenia impact exercise engagement and maintenance. Virtual Physical Activity Can Enhance Life (Virtual PACE-Life), a multicomponent walking intervention guided by self-determination theory (SDT), was developed to target CRF in this population while addressing motivational difficulties. Virtual PACE-Life includes live video-delivered group walking sessions, Fitbit activity tracking, recommendations for home-based walking sessions, goal setting, and if-then plans. The present study was a 16-week pilot randomized controlled trial that evaluated the impact of Virtual PACE-Life against Fitbit Alone in a sample of 37 participants with schizophrenia on intermediate targets (competence, autonomy, and relatedness satisfaction, autonomous motivation), proximal outcomes (Fitbit-measured steps/day and minutes spent walking), and the primary outcome (CRF using the 6-minute walk test). Blinded research staff completed assessments at baseline, midpoint, posttest, and one-month follow-up. Analysis of covariance and hierarchical linear regression analyses were used to evaluate group differences at each timepoint controlling for baseline. Attendance at Virtual PACE-Life groups was 58% and Fitbit adherence was above 70% in both conditions. Intent-to-treat results indicated greater competence and autonomy satisfaction for Virtual PACE-Life but not in relatedness satisfaction or autonomous motivation. There were no group differences in proximal or primary outcomes during the intervention period. Completer analyses showed improvements in steps/day and autonomous motivation favoring Virtual PACE-Life. Future research is needed to maximize the exercise and CRF benefits of virtual group-based exercise for persons with schizophrenia.

Racial disparities and predictors of functioning in schizophrenia.

Black Americans are diagnosed with schizophrenia spectrum disorders at more than twice the rate of White individuals and experience significantly worse outcomes following diagnosis. Little research has examined specific factors that may contribute to worse functional outcomes among Black Americans diagnosed with schizophrenia. One approach to understanding why racial disparities emerge is to examine established predictors of functioning in this population: neurocognition, social cognition, and symptom severity. The present study aims to broaden existing literature on racial differences within these domains by (a) examining racial differences in functioning and these established predictors of functioning (i.e., neurocognition, social, and symptom severity) and (b) investigating whether cognition and symptom domains similarly predict functioning between Black and White Americans with schizophrenia. Sixty-six participants' baseline neurocognition, social cognition, symptom severity, and functioning were assessed. Black participants demonstrated lower neurocognition scores and higher levels of disorganized symptoms relative to White participants. No racial differences in functioning or social cognition were observed. Further, race did not moderate the relationship between any of these established predictors and functioning outcomes. The largely nonsignificant differences in known predictors of functioning highlight the need to explore further domains that may be more relevant for understanding racial disparities in schizophrenia. Considering that psychosocial treatments for schizophrenia spectrum disorders often focus on cognition, these results underscore the importance of identifying whether these domains or other treatment targets may be better in addressing racial disparities in functioning. Possible areas of exploration for future work (e.g., structural factors, racism-related stress) are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial.

People with schizophrenia exhibit reduced alpha oscillations and frontotemporal coordination of brain activity. Alpha oscillations are associated with top-down inhibition. Reduced alpha oscillations may fail to censor spurious endogenous activity, leading to auditory hallucinations. Transcranial alternating current stimulation (tACS) at the alpha frequency was shown to enhance alpha oscillations in people with schizophrenia and may thus be a network-based treatment for auditory hallucinations. We conducted a double-blind, randomized, placebo-controlled pilot clinical trial to examine the efficacy of 10-Hz tACS in treating auditory hallucinations in people with schizophrenia. 10-Hz tACS was administered in phase at the dorsolateral prefrontal cortex and the temporoparietal junction with a return current at Cz. Patients were randomized to receive tACS or sham for five consecutive days during the treatment week (40 min/day), followed by a maintenance period, during which participants received weekly tACS (40 min/visit) or sham. tACS treatment reduced general psychopathology (p < 0.05, Cohen's d = -0.690), especially depression (p < 0.005, Cohen's d = -0.806), but not auditory hallucinations. tACS treatment increased alpha power in the target region (p < 0.05), increased the frequency of peak global functional connectivity towards 10 Hz (p < 0.05), and reduced left-right frontal functional connectivity (p < 0.005). Importantly, changes in brain functional connectivity significantly correlated with symptom improvement (p < 0.05). Daily 10 Hz-tACS increased alpha power and altered alpha-band functional connectivity. Successful target engagement reduced depression and other general psychopathology symptoms, but not auditory hallucinations. Considering existing research of 10Hz tACS as a treatment for major depressive disorder, our study demonstrates its transdiagnostic potential for treating depression.

Targeting Physical Health in Schizophrenia: Results from the Physical Activity Can Enhance Life (PACE-Life) 24-Week Open Trial.

Poor health and low cardiorespiratory fitness (CRF) contribute substantially to the shortened lifespan of individuals with schizophrenia spectrum disorders (SSDs). Increasing physical activity has demonstrated value; however, there are limited interventions that are accessible and adequately address motivational challenges. This paper reports on an open trial of Physical Activity Can Enhance Life (PACE-Life), a motivational theory-based manualized multicomponent walking intervention. The primary aim was to examine the feasibility of implementing PACE-Life through meeting the recruitment target (n=14), attendance and adherence rates, and participant feedback. The secondary aim was to assess the impact of PACE-Life on intermediate targets (autonomous motivation and satisfaction of autonomy, relatedness, and competence needs), proximal outcomes (Fitbit steps/day and minutes spent walking), the primary outcome (CRF), and secondary outcomes (loneliness, symptoms, resting heart rate, blood pressure, weight, body mass index, and hip and waist circumference). Seventeen participants with SSDs enrolled in a 24-week open trial. Assessments occurred at baseline, midpoint, post-test, and one-month follow-up. The recruitment target was exceeded, the group attendance rate was 34%, Fitbit adherence rate was 54%, and participant feedback indicated satisfaction with the intervention as well as a positive group environment. There was a large improvement in the primary outcome of CRF with 77% of participants achieving clinically significant improvement at post-test. Small and medium effect size increases were observed in autonomous motivation and satisfaction of autonomy, relatedness, and competence needs. Fitbit data and secondary outcomes generally remained unchanged or worsened during the intervention. Results from this open trial indicate that PACE-Life leads to meaningful changes in CRF among people with SSDs.

Systematic Quality Improvement and Metabolic Monitoring for Individuals Taking Antipsychotic Drugs.

OBJECTIVE: The authors sought to increase the rate of cardiometabolic monitoring for patients receiving antipsychotic drugs in an academic outpatient psychiatric clinic serving people with serious mental illness. METHODS: Using a prospective quasi-experimental, interrupted time-series design with data from the electronic health record (EHR), the authors determined metabolic monitoring rates before, during, and after implementation of prespecified quality improvement (QI) measures between August 2016 and July 2017. QI measures included a combination of provider, patient, and staff education; systematic barrier reduction; and an EHR-based reminder system. RESULTS: After 1 year of QI implementation, the rate of metabolic monitoring had increased from 33% to 49% (p<0.01) for the primary outcome measure (hemoglobin A1C and lipid panel). This increased monitoring rate was sustained for 27 months beyond the end of the QI intervention. More than 75% of providers did not find the QI reminders burdensome. CONCLUSIONS: Significant improvement in the rate of metabolic monitoring for people taking antipsychotic drugs can be achieved with little added burden on providers. Future research needs to assess the full range of patient, provider, and system barriers that prevent cardiometabolic monitoring for all individuals receiving antipsychotic drugs.

Neurophysiological substrates of configural face perception in schizotypy.

Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 ms after stimulus onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may represent a pathological deficit in the neurophysiology of face perception. Interestingly, healthy humans with schizophrenia-like experiences (schizotypy) also exhibit abnormal processing of face perception. Yet, it has remained unknown how schizotypy in healthy humans is associated with the neurophysiological substrates of face perception. Here, we recruited 35 healthy participants and assessed their schizotypy by the magical ideation rating scale. We used high-density electroencephalography to obtain ERPs elicited by a set of Mooney faces (face and non-face visual stimuli). We investigated median and mean reaction times and visual ERP components in response to the stimuli. We observed a significant difference in N170 amplitude between the two face-stimulus conditions and found that the measured schizotypy scores were significantly correlated with both reaction times and N170 amplitude in response to the face stimuli across all participants. Our results thus support the model of schizotypy as a manifestation of a continuum between healthy individuals and patients with schizophrenia, where the N170 impairment serves as a biomarker for the degree of pathology along this continuum.

Neighborhood socioeconomic status and racial disparities in schizophrenia: An exploration of domains of functioning.

Black Americans are disproportionately diagnosed with schizophrenia and experience worse objective functional outcomes (e.g., hospitalizations) than their White counterparts. However, we have a limited understanding of the psychological pathways through which Black Americans with schizophrenia reach worse outcomes. This study assessed race and domains of functioning (e.g., neurocognition, functional capacity) known to be associated with objective outcomes in a sample of 108 non-Hispanic Black and 61 non-Hispanic White individuals with schizophrenia-spectrum disorders from the Social Cognition Psychometric Evaluation (SCOPE) study. Three primary findings emerged: First, Black participants showed lower scores than White participants on measures of neurocognition(NC), social cognition(SC), and everyday living skills, but not social skills or community functioning. Second, neighborhood socioeconomic status (SES) explained 21% of the relationship between race and NC but did not mediate the relationship between race and SC or everyday living skills. Finally, prior research has established that NC, SC, social skills, and everyday living skills predict community functioning in individuals. Finally, prior research has established that NC, SC, social skills, and everyday living skills predict community functioning in individuals with schizophrenia. In our sample, after controlling for neighborhood SES, race did not moderate the relationships of NC, SC, social skills, or everyday living skills to community functioning. This indicates that relationships between these domains are comparably strong across Black and White Americans. Taken together, these findings show that NC, SC, and everyday living skills may be important areas to explore in regards to racial disparities in schizophrenia. More research, especially incorporating nuanced race- and SES-related variables, is needed to understand how to best intervene and improve real-world outcomes for Black Americans with schizophrenia.

Psychometric properties of the Observable Social Cognition Rating Scale (OSCARS): Self-report and informant-rated social cognitive abilities in schizophrenia.

Individuals with schizophrenia spectrum disorders (SSD) consistently show deficits in social cognition (SC) which is associated with real world outcomes. Psychosocial treatments have demonstrated reliable improvements in SC abilities, highlighting the need for accurate identification of SC deficits for efficient and individualized treatment planning. To this end, the Observable Social Cognition Rating Scale (OSCARS) is an 8-item scale with both self and informant versions. This study investigated psychometric properties of the OSCARS as both a self and informant-reported scale in a large sample of SSD (n = 382) and individuals without a psychiatric diagnosis (n = 289). A two-factor structure (Social Cognitive Bias and Social Cognitive Ability) of the OSCARS demonstrated acceptable model fit with good internal consistency for both self- and informant-report. The OSCARS had adequate convergent, external, and predictive validity. Area Under the Curve (AUC) values suggest the OSCARS has some value in identifying individuals with impaired SC and social competence, although stronger AUC values were demonstrated when identifying individuals with impaired real-world functioning. Overall, psychometric properties indicate the OSCARS may be a useful first-step tool for clinicians to detect functioning deficits in SSD and efficiently identify individuals in need of additional assessment or psychosocial interventions.

Confidence, performance, and accuracy of self-assessment of social cognition: A comparison of schizophrenia patients and healthy controls.

Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is common in healthy individuals as well. This study examines the correlations between performance on a social cognitive test, confidence in performance, effort allocated to the task, and correlates of confidence in patients with schizophrenia and healthy controls (HC). Measures included self-reports of depression, social cognitive ability, and social functioning. A performance-based emotion recognition test assessed social cognitive performance and provided the basis for confidence judgments. Although schizophrenia patients had reduced levels of overall confidence, there was a substantial subset of schizophrenic patients who manifested extreme overconfidence and these people had the poorest performance and reported the least depression. Further, a substantial number of HC over-estimated their performance as well. Patients with schizophrenia, in contrast to HC, did not adjust their effort to match task difficulty. Confidence was minimally related to task performance in patients but was associated with more rapid decisions in HC, across both correct and incorrect responses. Performance on social cognitive measures was minimally related to self-reports of social functioning in both samples. These data suggest global self-assessments are based on multiple factors, with confidence affecting self-assessments in the absence of feedback about performance.

Depression predicts self assessment of social function in both patients with schizophrenia and healthy people.

BACKGROUND: Impairments in social functioning are central to Schizophrenia (SCZ). Patients with SCZ have challenges in the ability to evaluate their functioning. A correlate of self-assessments in SCZ is depression, wherein negligible depression predicts overestimation. Healthy individuals misestimate their functioning, but mild dysthymia predicts accuracy. We examined depression, gender, and schizophrenia as predictors of self-reported everyday functioning. METHODS: 218 people with SCZ and 154 healthy controls self-reported their social functioning. They self-reported their depression with the Beck Depression Inventory (BDI) and their social cognitive ability on the Observable Social Cognition Rating Scale (OSCARS). RESULTS: 64% of subjects were male. Schizophrenia patients reported more depression, poorer social functioning, and worse social cognition. Linear regression analyses revealed significant correlations between self-reported social functioning and BDI scores, which also predicted self-reported social cognition. There was no significant effect of sex on self-reports of social functioning or social cognition. Finally, when BDI and OSCARS were directly compared to diagnosis and sex for prediction of self-reported social functioning, there was no impact of diagnosis or sex. IMPLICATIONS: Self-reported interpersonal functioning is determined by current depression. Both healthy people and people with schizophrenia index their social functioning and their social cognitive by their level of depression.

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests.

Developmental regulation of the NMDA receptor subunits, NR3A and NR1, in human prefrontal cortex.

Subunit composition of N-methyl-D-aspartate-type glutamate receptors (NMDARs) dictates their function, yet the ontogenic profiles of human NMDAR subunits from gestation to adulthood have not been determined. We examined NMDAR mRNA and protein development in human dorsolateral prefrontal cortex (DLPFC), an area in which NMDARs are critical for higher cognitive processing and NMDAR hypofunction is hypothesized in schizophrenia. Using quantitative reverse transcriptase-polymerase chain reaction and western blotting, we found NR1 expression begins low prenatally, peaks in adolescence, yet remains high throughout life, suggesting lifelong importance of NMDAR function. In contrast, NR3A levels are low during gestation, surge soon after birth, and decline progressively through adolescence and into adulthood. Because NR3A subunits uniquely attenuate NMDAR-mediated currents, limit calcium influx, and suppress dendritic spine formation, high levels during early childhood may be important for regulating neuroprotection and activity-dependent sculpting of synapses. We also examined whether subunit changes underlie reduced NMDAR activity in schizophrenia. Our results reveal normal NR1 and NR3A protein levels in DLPFC from schizophrenic patients, indicating that NMDAR hypofunction is unlikely to be maintained by gross changes in NR3A-containing NMDARs or overall NMDAR numbers. These data provide insights into NMDAR functions in the developing CNS and will contribute to designing pharmacotherapies for neurological disorders.

Effects of oxytocin on empathy, introspective accuracy, and social symptoms in schizophrenia: A 12-week twice-daily randomized controlled trial.

The effects of intranasal oxytocin, a neuropeptide involved in prosocial behavior and modulation of neural networks underlying social cognition and emotion regulation, have been studied in schizophrenia. We tested the hypothesis that twice-daily intranasal oxytocin administered for 12-weeks would improve tertiary and exploratory outcomes of self-reported social symptoms, empathy and introspective accuracy from the Jarskog et al. (2017) randomized controlled trial. Sixty-eight stable outpatients with schizophrenia or schizoaffective disorder were randomized to receive oxytocin (24 IU twice daily) or placebo. Introspective accuracy was assessed with the Specific Level of Functioning Scale and the Interpersonal Perception Task. Empathy was assessed with the Interpersonal Reactivity Index (IRI), and social symptoms were assessed with the Liebowitz Social Anxiety Scale and the Green et al. Paranoid Thoughts Scales. Outcomes were assessed at baseline, six, and twelve weeks. Results demonstrated limited effect of oxytocin with some improvement on the IRI Perspective-Taking Subscale. No additional between-group differences emerged on self-reported symptoms, empathy, or introspective accuracy.