Objective: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic, has 2 initiation options: 1-day (AL NanoCrystal Dispersion [ALNCD] injection plus 30 mg oral aripiprazole on day 1 only) and 21-day (15 mg oral aripiprazole for 21 days). This post hoc analysis assessed the safety and tolerability of both initiation approaches.
Methods: We analyzed data from the first 4 weeks of 2 AL studies, one using the 1-day initiation regimen (conducted between November 2017 and March 2019) and the other using the 21-day initiation regimen (conducted between December 2011 and March 2014). Outcomes of interest during the matched 4-week period included the likelihood of adverse events (AEs), including those associated with discontinuation, rated as serious, or of special interest (injection site reactions [ISRs] and akathisia).
Results: The 1-day (n = 99) and 21-day (n = 415) initiation regimens had comparable rates of AEs (57.6% and 52.0%, respectively; most were mild), serious AEs (2.0% and 1.4%), and AEs leading to discontinuation (4.0% and 3.1%). The incidence of ISRs was 11.1% after the ALNCD injection (day 1) in the 1-day initiation regimen. ISR rates for the AL starting doses were 9.2% for the 1-day regimen (AL 1064 mg on day 8) and 3.9% for the 21-day regimen (AL 441 mg/882 mg on day 1). Rates of akathisia were 9.1% and 11.1% for the 1-day and 21-day regimens, respectively. One patient discontinued because of an ISR in the 21-day study, and 2 patients in the 21-day study discontinued because of akathisia. Mean changes from baseline in week 4 Positive and Negative Syndrome Scale total scores were -17.4 (1-day) and -19.5 (21-day).
Conclusions: Four-week safety and tolerability were similar following the initiation of AL with either the 1-day or 21-day regimen, supporting the utility of both initiation regimens. Engaging patients in discussions regarding options for initiating AL may help facilitate shared decision-making and personalization of treatment for patients with schizophrenia.
Trial Registration: ClinicalTrials.gov identifiers: NCT03345979 and NCT01469039.

UNASSIGNED: In patients with schizophrenia spectrum disorder (SSD), the lifetime prevalence of self-harm (SH) and non-suicidal self-injury (NSSI) is currently uncertain. The primary aim of this review was to provide a synthesis of the existing literature concerning the prevalence of SH/NSSI in individuals with SSD, and individuals at clinical high risk of psychosis (CHR-P). Secondary aims were to investigate methods, severity, and functions of self-injurious behavior in these populations.
UNASSIGNED: Studies quantifying the prevalence of SH/NSSI in individuals with SSD or at CHR-P were included in this review. MEDLINE, EMBASE, and PsycInfo were searched for eligible studies June 10, 2022 and systematically screened by two independent reviewers. Risk of bias was assessed using the Joana Briggs Institute Critical Appraisal Checklist for Prevalence Studies by two independent reviewers. A meta-analysis of the lifetime prevalence of SH/NSSI was conducted using generalized linear mixed model with the logit transformation.
UNASSIGNED: Thirty-two studies were included in this review (n = 15 440), 4 of which included individuals at CHR-P (n = 397). The meta-analysis showed a pooled lifetime prevalence of SH of 31.0% (95% CI: 22.1%; 41.6%) in individuals with SSD (n = 2822) and 39.7% (95% CI: 17.5%; 70.0%) in individuals at CHR-P (n = 397). These estimates should be interpreted with caution due to substantial heterogeneity. Cutting was the most frequent method of SH/NSSI and SH command hallucinations may be an overlooked cause of self-injurious behavior in these patients.
UNASSIGNED: Self-injurious behavior is a highly prevalent, and possibly overlooked concern, in individuals with SSD and at CHR-P.

UNASSIGNED: Studies have linked auditory hallucinations (AH) in schizophrenia spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI).
UNASSIGNED: We included patients with SCZ with (AH+; n = 59) and without (AH-; n = 81) current AH, and 140 age- and sex-matched controls. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from 39 fiber tracts. We used principal component analysis (PCA) to identify general factors of variation across fiber tracts and DTI metrics. Regression models adjusted for sex, age, and age2 were used to compare tract-wise DTI metrics and PCA factors between AH+, AH-, and healthy controls and to assess associations with clinical characteristics.
UNASSIGNED: Widespread differences relative to controls were observed for MD and RD in patients without current AH. Only limited differences in 2 fiber tracts were observed between AH+ and controls. Unimodal PCA factors based on MD, RD, and AD, as well as multimodal PCA factors, differed significantly relative to controls for AH-, but not AH+. We did not find any significant associations between PCA factors and clinical characteristics.
UNASSIGNED: Contrary to previous studies, DTI metrics differed mainly in patients without current AH compared to controls, indicating a widespread neuroanatomical distribution. This challenges the notion that altered DTI metrics within the LAPC is a specific feature underlying AH.

UNASSIGNED: Long-acting injectable (LAI) antipsychotics improve patient outcomes and are recommended by treatment guidelines for patients with limited medication adherence in schizophrenia spectrum, bipolar, and other psychotic disorders. Reports of LAI antipsychotic use in these disorders and if use aligns with treatment guidelines are lacking. This study aimed to report patient characteristics associated with LAI antipsychotic use in these disorders.
UNASSIGNED: Retrospective observational study of patients ≥18-years-old with bipolar or psychotic disorders at a large, integrated, community-based health system. Patient demographic and clinical characteristics served as exposures for the main outcome of adjusted odds ratio (aOR) for LAI versus oral antipsychotic medication use from January 1, 2017 to December 31, 2023.
UNASSIGNED: There were N = 2685 LAI and N = 31 531 oral antipsychotic users. Being non-white (aOR = 1.3-2.0; P < .0001), non-female (aOR = 1.5; P < .0001), from a high deprivation neighborhood (NDI, aOR = 1.3; P < .0007), having a higher body mass index (BMI, aOR = 1.3-1.7; P < .0009), having a schizophrenia/schizoaffective (aOR = 5.8-6.8; P < .0001), psychotic (aOR = 1.6, P < .0001), or substance use disorder (aOR = 1.4; P < .0001), and outpatient psychiatry (aOR = 2.3-7.5; P < .0001) or inpatient hospitalization (aOR = 2.4; P < .0001) utilization in the prior year with higher odds and age ≥40 (aOR = 0.4-0.7; P < .0001) or bipolar disorder (aOR = 0.9; P < .05) were associated with lower odds of LAI use. Non-white, non-female, age 18-39, and high NDI patients had higher LAI use regardless of treatment adherence markers. Smoking and cardiometabolic markers were also associated with LAI use.
UNASSIGNED: Demographic and clinical factors are associated with increased LAI use irrespective of treatment adherence. Research on utilization variation informing equitable formulation use aligned with treatment guideline recommendations is warranted.

Clozapine is the most effective medication for the management of treatment-resistant schizophrenia and schizoaffective disorder, and its discontinuation can pose significant challenges in treatment. We present a patient with a diagnosis of schizoaffective disorder who was stable on clozapine for a decade until discontinuation due to thrombocytopenia. She experienced a relapse of her illness, presenting with psychotic and catatonic features with poor oral intake and physical health complications requiring a lengthy admission to the hospital. There was a poor response to alternative antipsychotics and a full course of electroconvulsive therapy. Intramuscular (IM) clozapine was initiated due to catatonia and refusal to accept oral medications. After receiving 10 doses of IM clozapine, she started accepting oral clozapine and made a full recovery within a few weeks. The low platelet count was persistent, and a bone marrow biopsy showed results consistent with immune thrombocytopenia being the cause of that low platelet count.

OBJECTIVE: This study proposed and evaluated a theoretical model for exploring the relationships between neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning in individuals with chronic schizophrenia.
METHODS: The study recruited 229 individuals given a diagnosis of schizophrenia and schizoaffective disorders from outpatient clinics and the day ward of a mental health hospital. After informed consent was obtained, the participants underwent assessments using the backward digit span, the digit symbol, and measures of self-defeatist beliefs, experiential negative symptoms, and social functioning. A structural equation model was applied to assess the fitness of the hypothesized model, with indices such as the goodness-of-fit index, comparative fit index, root mean square error of approximation, and standardized root mean square residual being used for model evaluation.
RESULTS: The hypothesized model had an adequate fit. The study findings indicated that neurocognition might indirectly influence self-defeatist beliefs through its effect on experiential negative symptoms. Contrary to expectations, the study did not observe a direct influence of neurocognition, self-defeatist beliefs, or negative symptoms on social functioning. The revised model revealed the role of experiential negative symptoms in mediating the association between neurocognition and social functioning. However, self-defeatist beliefs did not significantly affect social functioning.
CONCLUSIONS: Before modifying negative thoughts, enhancement of self-awareness ability can help improve negative symptoms and thereby improve the performance of social functions. Future research should develop a hierarchical program of negative symptoms, from cognition rehabilitation to enhancement of self-awareness, and end with modifying maladaptive beliefs.

Mobile sensing-based depression severity assessment could complement the subjective questionnaires-based assessment currently used in practice. However, previous studies on mobile sensing for depression severity assessment were conducted on homogeneous mental health condition participants; evaluation of possible generalization across heterogeneous groups has been limited. Similarly, previous studies have not investigated the potential of free-living audio data for depression severity assessment. Audio recordings from free-living could provide rich sociability features to characterize depressive states. We conducted a study with 11 healthy individuals, 13 individuals with major depressive disorder, and eight individuals with schizoaffective disorders. Communication logs and location data from the participants\' smartphones and continuous audio recordings of free-living from a wearable audioband were obtained over a week for each participant. The depression severity prediction model trained using communication log and location data features had a root mean squared error (rmse) of 6.80. Audio-based sociability features further reduced the rmse to 6.07 (normalized rmse of 0.22). Audio-based sociability features also improved the F1 score in the five-class depression category classification model from 0.34 to 0.46. Thus, free-living audio-based sociability features complement the commonly used mobile sensing features to improve depression severity assessment. The prediction results obtained with mobile sensing-based features are better than the rmse of 9.83 (normalized rmse of 0.36) and the F1 score of 0.25 obtained with a baseline model. Additionally, the predicted depression severity had a significant correlation with reported depression severity (correlation coefficient of 0.76, p < 0.001). Thus, our work shows that mobile sensing could model depression severity across participants with heterogeneous mental health conditions, potentially offering a screening tool for depressive symptoms monitoring in the broader population.

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown.
METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis.
RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages.
CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.

UNASSIGNED: Studies using human postmortem tissue and imaging with positron emission tomography (PET) support a low hippocampal availability of the α7 nicotinic acetylcholine receptor (α7-nAChR) in psychotic conditions, particularly in schizophrenia or schizoaffective disorder (nonaffective psychosis). If validated further, the finding may have implications for clinical diagnosis and treatment.
UNASSIGNED: To test for lower availability of the α7-nAChR in the hippocampus of individuals with recent-onset psychosis compared with healthy control individuals and its association with lower cognitive performance or higher psychotic symptom burden within recent-onset psychosis.
UNASSIGNED: In this cross-sectional study, healthy individuals without history of psychosis and patients within 10 years of a first onset of psychotic disorder were recruited from the greater Baltimore, Maryland, and Washington, DC, area. Fluorine 18-labeled ASEM ([18F] ASEM) PET data were acquired from participants enrolled between March 1, 2014, and July 31, 2023, from an academic research institution. Data acquired between March 1, 2014, and January 31, 2018 (n = 26), were published as a pilot study and were combined with new data acquired between January 1, 2019, and July 31, 2023 (n = 33).
UNASSIGNED: Regional [18F]ASEM total distribution volume (VT) that measures α7-nAChR availability, global cognition composite score, and total scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms.
UNASSIGNED: A total of 59 participants (30 women [51%]; mean [SD] age, 25.5 [5.2] years), including 35 with recent-onset psychosis and 24 healthy controls, completed the study. In age-adjusted analyses, lower hippocampal [18F]ASEM VT was found in individuals with recent-onset psychosis (mean [SE], 17.87 [0.60]) compared with healthy controls (mean [SE], 19.82 [0.73]) (P = .04). In addition, [18F]ASEM VT was lower in individuals with nonaffective psychosis (mean [SE], 16.30 [0.83]) compared with healthy controls (P = .006) or those with affective psychosis (mean [SE], 19.34 [0.80]) (P = .03). Across recent-onset psychosis and after controlling for age, lower hippocampal [18F]ASEM VT was associated with more positive (r = -0.44; P = .009) but not negative symptoms, and higher hippocampal VT was associated with better global cognition composite score (r = 0.38; P = .03).
UNASSIGNED: In this cross-sectional study of individuals with recent-onset psychosis compared with healthy controls, a lower hippocampal α7-nAChR availability was found in recent-onset psychosis, and its availability was lower in those with nonaffective vs affective psychosis. Further study of the association between low availability of the α7-nAChR and recent-onset psychosis is warranted toward informing diagnostic or therapeutic strategies related to these findings.

BACKGROUND: Recent research has demonstrated that the dorsal striatum is directly associated with the integration of cognitive, sensory-motor, and motivational/emotional data. Disruptions in the corticostriatal circuit have been implicated in the pathophysiology of psychosis. The dorsal striatum was reported to show lateralized pathology in psychotic disorders. In this study, we aimed to analyze the laterality of the dorsal striatum with texture analysis of T2-weighted magnetic resonance imaging (MRI) images from schizoaffective disorder (SAD) patients.
METHODS: Twenty SAD patients, met the inclusion criteria and had available cranial MRI data were assigned as the patient group. Twenty healthy individuals were determined as the control group. Texture analysis values were obtained from striatum region of interests (ROI) generated from T2-weighted MRI images. Data are presented as mean and standard deviation. The suitability of the data for normal distribution was analyzed with the Kolmogorov-Smirnov test. Analysis of variance (ANOVA) test (Post Hoc TUKEY) was employed to compare the group data based on test findings.
RESULTS: There was no significant difference between the groups in terms of gender and age. There were differences in the values of texture analysis parameters of both caudate and putamen nuclei in comparison to controls. We identified differences in the left dorsal striatum nuclei in SAD. The differences in the putamen were more and more pronounced than in the caudate.
CONCLUSIONS: Texture analyses suggest that the left dorsal striatum nuclei may be different in SAD patients. Further studies are needed to determine the pathophysiology of SAD and how it may affect disease treatment.