Unpacking the pathophysiological mechanisms of schizophrenia is necessary for advancing prediction, prevention, and treatment efforts. Mechanisms can be identified using easy-to-use and scalable clinical biomarkers, which reflect illness processes. Pupillometry is one such biomarker. Blunted dilation related to cognitive demand has been interpreted as a metric of diminished effort in schizophrenia, while blunted constriction to light has been interpreted as a metric of altered autonomic balance in schizophrenia. However, these 2 sets of findings may also reflect a common mechanism of schizophrenia. Therefore, this study aimed to explore the association between blunted cognitive dilation and blunted constriction to light to provide a parsimonious mechanism of autonomic and effort disturbances experienced by individuals with schizophrenia. We assessed light-induced constriction and cognitive dilation during a double-step task in individuals with schizophrenia (n = 84) and demographically matched healthy controls (HC, n = 69), compared these metrics between groups, and computed their correlation within each group. Replicating prior findings, dilation and constriction were blunted in schizophrenia relative to HC. Blunted constriction and dilation were positively correlated in schizophrenia but not HC (although the 2 correlations did not differ significantly). Findings provide, for the first time, preliminary support of a common mechanism linking blunted pupil constriction to light and dilation to cognitive demands in schizophrenia. We propose that individuals with schizophrenia may exhibit impaired top-down modulation of autonomic control. Future studies are needed to validate this proposed mechanism.
Background: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder and represents one of the strongest known genetic risk factors for psychosis. Social cognition (SC) deficits are a core feature of schizophrenia and are strongly associated with functional outcomes. In individuals affected by 22q11.2DS and psychotic symptoms, SC impairments may emerge early; however, direct comparisons between patients with 22q11.2DS with psychotic symptoms and those with schizophrenia remain limited. Methods: In this case–control study, we investigated 21 patients with 22q11.2DS and active psychotic symptoms and 21 outpatients with schizophrenia and active psychotic symptoms recruited from the outpatient clinics of Sant’Andrea Hospital, Rome. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive and social cognitive functioning were evaluated using the Cognitive Assessment Interview. Results: Patients with schizophrenia showed significantly higher severity of positive, general, cognitive, excitement, and depression symptoms (all P < .05). In contrast, patients with 22q11.2DS exhibited more pronounced SC impairment (U = 81.00, P < .001). In the 22q11.2DS group, SC was associated with multiple cognitive and clinical domains, including working memory, attention/vigilance, processing speed, reasoning/problem solving, and PANSS total score. Correlation analyses further revealed stronger associations between negative symptoms and cognitive domains in 22q11.2DS group compared with schizophrenia group. Conclusions: In this study, patients with 22q11.2DS and patients with schizophrenia showed partially distinct profiles of psychopathology and SC. While schizophrenia was characterized by greater overall symptom severity, 22q11.2DS was associated with more pronounced social cognitive impairment.
Reduced social networks contribute to social dysfunction and loneliness in schizophrenia. However, standard measures of social networks are broad and provide limited information about network structure or characteristics of network members. This study used egocentric social network analysis (SNA)-an approach that has rarely been applied in schizophrenia-to evaluate whether it provides added explanatory value for social functioning and loneliness. We did not specify directional hypotheses. Individuals with schizophrenia (n = 54) and controls (n = 41) completed a social network interview. SNA metrics derived from the interview included constraint (network interconnectedness), education and race homophily (similarity between participants and network members), and ego-betweenness (the extent to which the participant connects otherwise unconnected alters). Hierarchical regressions within schizophrenia examined associations between SNA metrics, social functioning, and loneliness after accounting for social network size and negative symptoms. People with schizophrenia had greater constraint than controls, suggesting more redundant networks. After accounting for social network size and negative symptoms, greater constraint (β = -.61, P = .01) and greater ego-betweenness (β = -.35, P = .02) were associated with greater social dysfunction. Lower education homophily (β = .35, P = .01) was associated with greater loneliness. Overall, SNA metrics explained an additional 12% of the variance in social functioning and 15% in loneliness. These findings suggest that SNA metrics could serve as more precise indicators of social impairment in schizophrenia than standard measures of social networks and clinical variables alone.
We utilized data from the 2021 Global Burden of Disease (GBD) Study to (i) provide estimates of the incidence, prevalence, and illness-related burden associated with schizophrenia; (2) examine how these rates have changed from 1990 to 2021; and (3) explore the association of these rates with several country-level variables (eg, access/quality of healthcare systems). The GBD study provides estimates for the incidence, prevalence, and disability-adjusted life years (DALYs) associated with 371 illness, injuries, and risk factors by age and sex across 204 countries and territories. We examined data from the GBD 2021 study to describe the global epidemiology of schizophrenia as well as the association between metrics of schizophrenia epidemiology and country-level variables previously associated with these metrics. In 2021, the global age-standardized incidence, prevalence, and DALY rates were 15.4, 277.7, and 177.8 per 100 000 individuals, respectively. Between 1990 and 2021, global incidence rates (both age-standardized and crude) declined, whereas crude prevalence and DALY rates per 100 000 increased and age-standardized prevalence and DALYs remained unchanged. However, these findings varied by age, gender, and geography. Changes in country-level variables between 1990-2021 (eg, alcohol use and per capita income) were associated with changes in incidence, prevalence, and DALY rates over this same time period. Schizophrenia remains a significant health concern worldwide. Our results highlight the need for health systems to prepare to address the growing prevalence of schizophrenia which may be greatest among older adults, and especially older women.
Heterogeneity in schizophrenia spectrum disorders is a major challenge to implementing personalized medicine and uncovering etiological pathways. Recent work identified subtypes of schizophrenia that exhibit unique patterns of clinical symptoms and features using a common clinical scale. The current study sought to: (1) replicate prior identification of subtypes using the Positive and Negative Syndrome Scale (PANSS) in a new cohort of people with schizophrenia; (2) further characterize differences between subtypes in symptoms, affect, cognition, functioning, and personality; and (3) determine if brain structure abnormalities vary across subtypes. Phenotypic data were obtained on 356 individuals with schizophrenia spectrum disorders. Structural brain magnetic resonance imaging data were acquired on a subset of 203 individuals with schizophrenia and 186 healthy people. A 2-step cluster analysis of PANSS data was used to identify subtypes of schizophrenia. Subtypes were compared on characteristics and brain volume. Clustering revealed 3 clusters aligning with previous subtypes: distress, negative, and low symptom. The distress subtype demonstrated higher levels of negative emotions, neuroticism, and schizotypal personality traits. The negative subtype exhibited more severe cognitive impairment, higher levels of disorganized and anhedonia symptoms, and worse functioning. Abnormalities in cortical volumes followed a gradient, the negative subtype demonstrated the largest number of cortical regions with smaller volume relative to healthy people, followed by the distress subtype, then the low symptom subtype. In contrast, smaller subcortical volumes were consistent across subtypes. Our findings support the presence of subtypes of schizophrenia spectrum disorders that differ in affect, cognition, functioning, personality, and brain structure.
The FDA approval in 2024 of the M1/M4 muscarinic receptor agonist xanomeline and trospium chloride (formerly known as KarXT) introduces a novel alternative to dopamine-receptor antagonism or partial agonism for schizophrenia treatment. All prior approved treatments rely on direct D2-receptor antagonism or partial agonism, limiting patient experiences to this mechanism. To explore this shift, we conducted a qualitative study examining patient experiences with a muscarinic receptor agonist. A companion report addresses perceived symptom changes; this report focuses on changes in quality of life (QoL) and medication satisfaction. A qualitative substudy was embedded in a larger 52-week open-label trial of xanomeline/trospium monotherapy in stable schizophrenia outpatients transitioned from standard antipsychotics. It included semi-structured interviews at 6 weeks (n = 70) and 6 months (n = 47) after initiating treatment. Narratives regarding change in QoL attributed to xanomeline/trospium and medication satisfaction were coded and categorized. Before starting xanomeline/trospium, most participants reported QoL challenges across the following domains: physical (95.7%), social (85.7%), and role (80.0%) functioning, and emotional well-being (74.3%). For the two most common issues in each domain, the percentage of participants who improved by 6 weeks ranged from 44.8% to 83.3%, increasing to 68.0% to 95.2% by 6 months after xanomeline/trospium initiation. Few participants worsened in any of these domains. Participants rated their satisfaction with xanomeline/trospium highly (mean = 8.1 out of 10 at both assessments) and 93.2% would recommend it to a friend. Xanomeline/trospium treatment was associated with meaningful improvements across QoL domains that participants had previously identified as challenging, and most participants reported high satisfaction with the medication. These findings should be interpreted cautiously given the open-label design, absence of a comparator group, and potential selection and attrition biases. Within these constraints, the results provide exploratory, participant-centered insights into treatment experience and suggest that muscarinic agonists may influence both symptomatic and functional aspects of schizophrenia, warranting further controlled investigation.
Heterogeneity in schizophrenia is significant but remains poorly understood. Treatment strategies have not evolved beyond one-size-fits-all approaches, often delaying the discovery of effective treatments and better outcomes. The deficit syndrome was proposed as a more homogenous subtype of the illness that is characterized by primary and enduring negative symptoms. We reviewed Magnetic Resonance Imaging (MRI) studies examining brain structure, function, and neurometabolism in deficit syndrome with the goal of identifying unique brain signatures for this subtype of schizophrenia. Systematic Review of MRI studies published between 1999 and 2024 on the deficit syndrome. Potentially unique features of the deficit syndrome include nucleus accumbens and cerebellar gray matter volume deficits, reduced uncinate fasciculus fractional anisotropy, fronto-parietal and default mode network dysconnectivity, altered global efficiency, and shortest path-length in brain network organization. Further, abnormalities in cerebellar culmen volume and cerebellar spontaneous activation may differ only in degree between patient groups. Many findings warrant replication and must be interpreted with caution. The deficit syndrome is hypothesized to be different from other forms of schizophrenia and more homogenous in its pathophysiology. Magnetic Resonance Imaging studies examining neurobiological group differences show conflicting results; some report that the deficit syndrome may be distinct, while others find that brain pathology is more severe or shared across subtypes. No MRI studies have directly tested if inter-individual heterogeneity in brain pathology is lower in the deficit syndrome, which would be necessary to determine if this clinically more homogenous subtype is also neurobiologically more homogenous.
Extrapyramidal symptoms (EPS) are common side effects of antipsychotic medications and can contribute to medication non-adherence and subsequent relapse in schizophrenia. Recent research suggests that inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), may serve as biomarkers for treatment response in schizophrenia. This exploratory study is a first look at the relationship between these inflammatory markers and EPS in patients with schizophrenia. Fifty patients with schizophrenia spectrum disorders were recruited, with 28 completing bloodwork. EPS was assessed using the Extrapyramidal Symptom Rating Scale (ESRS), and overall side effects were evaluated using the Glasgow Antipsychotic Side-Effect Scale (GASS). Blood samples were analyzed to calculate NLR, PLR, MLR, and SII. Monocyte count was negatively correlated with the ESRS akathisia subscale. Higher SII scores were significantly associated with self-reported parkinsonism and hyperkinesia. Patients on clozapine had significantly higher PLR and MLR compared to those on other antipsychotics. No significant association was found between total GASS scores and inflammatory markers. These findings suggest that certain inflammatory markers may be associated with specific EPS subscales. Further research with larger samples is needed to validate these results.
Affective disturbances are a core feature of schizophrenia, yet patients' capacity to experience momentary affective shifts in real-world settings remains underexplored. Although consummatory pleasure appears preserved, studies suggest low levels of positive affect and high levels of negative affect in daily life. Physical exercise provides an ecologically valid context for probing short-term affective reactivity. This study examined whether high-intensity interval training (HIIT) elicited greater affective change than an active control condition (ACC), whether baseline symptom levels were associated with affective state, and whether baseline symptoms moderated affective reactivity. In a randomized controlled trial, 69 outpatients with schizophrenia were randomized to a 12-week intervention involving either supervised HIIT or an ACC involving low-intensity, interactive video gaming. Affective state was assessed immediately before and after the 12th session using the Positive and Negative Affect Schedule (PANAS). Depressive (CDSS), negative symptoms (PANSS-N), and apathy (AES) were measured at baseline. Linear mixed-effects models tested Group × Time effects. HIIT did not produce significantly greater changes in positive or negative affect than the active control. Across interventions, participants showed increases in positive affect and decreases in negative affect. Higher baseline symptom levels were associated with lower pre-session positive affect. Exploratory analyses indicated that participants with more severe negative symptoms showed greater positive affective gains following HIIT. A single session of structured activity, regardless of intensity, was associated with small but measurable affective improvements. These findings highlight the value of accessible activity-based interventions for enhancing affective well-being in schizophrenia.
Schizophrenia spectrum disorders are known to affect the patient's functional performance. The functioning of those who are at familial risk for these disorders is less well understood. In this study, we compared the real-world functioning of adoptees with a genetic high-risk (HR) for schizophrenia spectrum disorders with adoptees without this risk (low-risk, LR). We hypothesized that the HR-group would have more difficulties in real-world functioning compared to the LR-group. The data were based on the Finnish Adoptive Family Study of Schizophrenia project. The study sample included 127 HR- and 130 LR-adoptees. An interview-based method, Strauss-Carpenter Level of Function (SCLF)-scale, was used to measure functional performance in a setup of adoptees living in comparable adoptive families. The SCLF-scale comprises domains for function, symptoms, social contacts, and work. The Structured Interview of Schizotypy was utilized in assessments of possible schizotypal traits of the HR- and LR-adoptees. No significant differences in the real-world functioning in total scores or scores of any SCLF domains were observed between HR- and LR-adoptees. Of single SCLF items, the HR-adoptees were characterized as being less likely to have achieved formal education and the LR-adoptees needed more help with their own basic needs. No differences were found in the real-world functioning between HR- and LR-populations. This indicates that the real-world functioning does not express one's genetic risk for schizophrenia spectrum disorders. Our findings highlight the importance of considering environmental factors when comparing genetically different groups.
Schizophrenia is a psychiatric condition often characterized by cognitive deficits which precede the onset of positive symptoms and contribute significantly to enduring functional impairments and poor quality of life. Those cognitive deficits can have a profoundly negative impact on daily activities such as social relationships and work functioning. Although pharmacological interventions remain central to the treatment of schizophrenia (SZ), they have a negligible impact on cognitive functioning. Yet multiple reviews and meta-analyses support the hypothesis that Aerobic Exercise (AE) could serve as an adjunctive, therapeutic intervention for these cognitive impairments. AE is recommended for individuals with Multi-episode Psychosis (MEP) and with First Episode Psychosis (FEP). This body of evidence indicates that for individuals with SZ, engagement in AE shows measurable enhancements in specific brain regions associated with key domains of neurocognitive functioning. AE has also been associated with improvements in neurobiological processes including increased BDNF, enhanced neurogenesis, and improved neural connectivity. These improvements were linked to key cognitive domains associated daily functioning such as attention, working memory, reasoning, speed of processing, and social cognition. Engagement in AE has also been associated with improvements in Activities of Daily Living, reductions in psychiatric symptoms, improvements in psychosocial functioning, and good quality of life. Endorsements and specific guidelines have been published worldwide from leading governmental health agencies and international professional psychiatric organizations. These recommendations have been summarized so that practitioners can implement AE programs for individuals with SZ using group and/or individually tailored interventions to boost motivation and enhance self-efficacy for engaging in AE.
First-person accounts (FPAs) provide multi-faceted insights into the lived social experiences of schizophrenia. We examined FPAs and third-person accounts (TPAs) using automated linguistic and network analyses to extract narrative patterns in relation to interpersonal difficulties. Narratives from 279 articles published in Schizophrenia Bulletin (1979-2025) were screened to identify 133 FPAs and 44 TPAs. Schizotypal Personality Questionnaire was used to assess syndromes of schizotypy expressed in the narratives. At least one cognitive-perceptual syndrome (ideas of reference, odd beliefs, magical thinking) was detected in every FPA (n = 133). Interpersonal difficulties (social anxiety, no close friends, constricted affect) were detected in 56 FPAs and designated as the "interpersonal difficulties" group. We used the Linguistic Inquiry and Word Count software to extract interpersonally relevant features: authenticity, emotional tone, pronoun use, social behavior, and confidence. Linguistic features of narratives in FPAs with and without interpersonal difficulties were compared using network analysis. Greater authenticity and lower confidence were detected in FPAs compared to TPAs. FPAs contained fewer social words and more "I" words than TPAs. FPAs with interpersonal difficulties were longer, more negative, and less linguistically formal than FPAs without interpersonal difficulties. Network analysis indicated a link between interpersonal difficulties and "voices." Narratives categorized by interpersonal difficulties exhibit distinct linguistic signatures revealed through automated linguistic tools and network analyses. Despite the vast range of topics in FPAs, these computational methods provide a robust quantitative framework for validating the lived experience of negative syndrome in schizotypy.
Long-acting injectable (LAI) antipsychotics improve adherence and reduce schizophrenia relapse rates vs oral antipsychotics (OAs) but remain underused. The ADVANCE study explored country-level differences in LAI use among healthcare professionals (HCPs), patients, and caregivers, to identify drivers of LAI use. ADVANCE included participants from Australia, Canada, China, Germany, Israel, South Korea, Spain, and the United States. Eligible HCPs spent ≥25% of their time in direct patient care, managed an adult population of whom ≥10% have schizophrenia, and treated patients prescribed LAIs. Patients aged ≥18 years and caregivers of adults living with schizophrenia who had tried/been offered an LAI were included. Participants completed a 30-minute survey. Systemic factors reported by HCPs (n = 791) associated with higher LAI use included being a physician vs nonphysician, having Hispanic/Latino/Spanish ethnicity, managing more adult patients with schizophrenia, and having more staff and nurse support. Nonadherence to OAs was the main HCP-reported reason for LAI recommendation. Patient characteristics, lack of available LAIs corresponding to OAs, and perceptions of patients' behavior were top reasons HCPs would not recommend an LAI. For patients (n = 470), symptom improvement and HCP recommendation, and for caregivers (n = 381), ease of injections, reduced hospitalizations, and fewer side effects were the main reasons for LAI acceptance. The top reason patients and caregivers declined LAIs was concern about side effects. Results from ADVANCE demonstrate that systemic and attitudinal factors influence LAI use by HCPs, and these factors vary by country. Enhancing HCP-patient communication may improve LAI acceptance.
Adolescent stress has been linked to an increased risk of developing psychiatric disorders, including schizophrenia. Previous findings from our group suggest that adolescent stress causes redox imbalance and functional impairments in parvalbumin (PV) interneurons and their associated perineuronal nets (PNNs) in the ventral hippocampus (vHip). These changes are associated with behavioral abnormalities, vHip hyperactivity, and dopamine system overdrive, mirroring observations in people with schizophrenia. Thus, we hypothesized that the antioxidant N-acetylcysteine (NAC) could mitigate schizophrenia-related alterations induced by adolescent stress in adult rats. Male Sprague-Dawley rats were subjected to a combination of daily footshock and restraint stress during adolescence [postnatal days (PD) 31-40]. NAC (900 mg/L) was administered through the drinking water either during (PD31-40) or after the adolescent stress (PD51-60). In adulthood (PD63), rats underwent behavioral tests to assess anxiety-like behaviors, social interaction, and cognition. From PD70, in vivo recordings of dopamine neurons in the ventral tegmental area (VTA) and immunostaining of PV, PNNs, and the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-Oxo-dG) in the vHip were performed. Adolescent stress causes, in adulthood, anxiety-like responses, deficits in sociability and cognitive function, increased VTA dopamine neuron population activity, reduced PV+ cells in the vHip, including those surrounded by PNNs, and enhanced expression of 8-Oxo-dG, particularly in PV+ cells. NAC treatment, whether administered during or after adolescent stress, significantly attenuated these alterations. NAC effectively mitigates schizophrenia-related changes induced by adolescent stress and may serve as a pharmacological intervention for prevention and treatment strategies.
This analysis of the multinational ADVANCE study evaluated how the healthcare professional's (HCP's) role and setting of care influence attitudes, perceptions, and utilization of long-acting injectable antipsychotics (LAIs) for schizophrenia treatment. A cross-sectional survey was conducted among HCPs from 8 countries, capturing data on practice characteristics, LAI prescribing behaviors, confidence, and challenges related to LAIs, and treatment objectives. A total of 791 HCPs were categorized by role (psychiatrist [n = 490] or psychiatric nonphysician [n = 301]) and by setting of care (inpatient [IP] psychiatric ward [n = 260], hospital-based outpatient [OP] clinic [n = 174], community/psychiatric OP clinic [n = 227], and independent practice [n = 107]). Psychiatrists were more likely to identify as early users of LAIs and demonstrated higher confidence with LAI use than psychiatric nonphysicians, who, despite lower confidence and lower likelihood of prescribing LAIs, reported higher patient acceptance rates at first recommendation. Among care settings, IP psychiatric ward HCPs had the highest likelihood of prescribing LAIs but the lowest confidence levels, whereas independent practice HCPs exhibited high confidence yet the lowest likelihood of prescribing LAIs. Independent practice HCPs reported having the least support staff and cited lack of time as a challenge to LAI use, suggesting that systemic barriers and HCP burden may influence LAI utilization. Together, these findings underscore the importance of tailored educational resources addressing both the HCP's role and practice environment to enhance confidence, facilitate effective patient discussions, and ultimately improve LAI utilization.
The distressing nature of delusional beliefs is considered key to their persistence. One potential mechanism underlying delusional distress is global emotion dysregulation. Global emotion dysregulation is associated with general psychotic symptom severity, but its specific relationship to delusional distress has yet to be closely examined. People with (n = 100) and without (n = 52) schizophrenia-spectrum disorders completed measures of delusional ideation (Peters Delusion Inventory; PDI-21) and global emotion dysregulation (Difficulties in Emotion Regulation Scale; DERS-16). Participants with schizophrenia also completed a measure of delusion severity (Psychotic Symptom Rating Scales; PSYRATS). Relationships between delusion severity and global emotion dysregulation were assessed with linear regression, controlling for age, sex, and group. Associations between delusional distress and aspects of emotion dysregulation were determined using stepwise linear regression. Global emotion dysregulation was significantly elevated in those with schizophrenia compared to non-clinical controls, across all subscales (P < .001). Emotion dysregulation was significantly associated with delusional distress on both the PDI-21 (P < .001) and PSYRATS (P < .001). Stepwise regressions revealed a specific association between limited access to emotion regulation strategies and delusional distress on both scales (P's < .001). Delusional distress remained associated with emotion dysregulation when controlling for delusional preoccupation, and emotion dysregulation was not significantly associated with delusional conviction on either scale. Emotion dysregulation, particularly the sense that there is little one can do to regulate themselves when upset, relates to delusional distress. Interventions that increase access to more emotion regulation strategies may help decrease distress associated with delusional thinking.
Cognitive impairment is a core feature of schizophrenia and a key determinant of functional outcome. Although conventional paper-and-pencil based cognitive assessments used in schizophrenia remained relatively static during most of the 20th century, this century has witnessed the emergence of innovative digital technologies that aim to enhance the ecological validity of performance-based assessments. This narrative review provides an overview of new technologies that show promise for enhancing the ecological validity of cognitive and functional assessments. We focus on 2 approaches that are particularly relevant for schizophrenia research: (1) digital functional capacity tasks, which use simulations to measure performance of important daily life activities (e.g., virtual shopping tasks), delivered both in-person and remotely, and (2) remote device-based assessments, which include self-administered cognitive tasks (e.g., processing speed test) or functionally-focused surveys regarding momentary activities and experiences (e.g., location, social context), as well as passive sensor-based metrics (e.g., actigraphy measures of activity), during daily life. For each approach, we describe the potential for enhancing ecological validity, provide examples of select measures that have been used in schizophrenia research, summarize available data on their feasibility and validity, and consider remaining challenges. Rapidly growing evidence indicates that digital technologies have the potential to enhance the ecological validity of cognitive and functional outcome assessments, and thereby advance research into the causes of, and treatments for, functional disability in schizophrenia.
Some but not other studies on oxytocin for schizophrenia, particularly those using a higher dose, indicate that oxytocin improves negative symptoms of schizophrenia. We performed an add-on randomized controlled trial to examine the effect of high-dose oxytocin, social skills training, and their combination in the treatment of negative symptoms and social dysfunction in schizophrenia. Fifty-one subjects with schizophrenia were randomized, employing a two-by-two design: intranasal oxytocin (24 IU X3/day) or placebo, and social skills training or supportive psychotherapy, for 3 weeks. The primary outcome was the difference in the total score from baseline to end-of-study of a semi-structured interview which assessed patients' social interactions in 3 scenarios: sharing a positive experience, sharing a conflict, and giving support when the experimenter shared a conflict. The interactions were scored using the Coding Interactive Behavior Manual (CIB), clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). No significant difference was found between groups in the total CIB or PANSS scores. The majority of comparisons in the different social interactions between oxytocin and placebo, and between social skills training vs supportive psychotherapy, were also nonsignificant. Social skills training reduced blunted affect and gaze. In post-hoc analyses of the support interaction, oxytocin improved synchrony and decreased tension, while in the positive interaction it improved positive affect and avoidance. None of these findings remained significant when controlling for multiple comparisons. In conclusion, oxytocin did not influence participants' social behavior, and was not effective in improving the symptoms of schizophrenia. Clinicaltrials.gov Identifier: NCT01598623.
Long-acting injectable antipsychotics (LAIs) improve adherence and reduce schizophrenia relapse rates. Data on which LAI attributes drive clinician preference are limited. In the DECIDE survey, 380 psychiatric clinicians (psychiatrists, psychiatric nurse practitioners, and physician assistants) were surveyed regarding preferences when selecting and initiating LAIs for patients with schizophrenia. Responses were analyzed by clinician use of LAIs (high [≥ 31% of their patients using LAIs] or low [≤ 14% of their patients using LAIs]) and mindset toward LAI use (early, severity reserved, adherence reserved, and LAI hesitant). Overall and across subgroups, side effects were the most important consideration when selecting a particular LAI, with 33% of clinicians ranking this as most important (26%-46% across subgroups). Clinician preference for the molecule was most often ranked least important (47% overall; 39%-59% across subgroups). A significantly higher proportion of clinicians with high vs low LAI use ranked product attributes as the most important consideration (26% vs 13%; P < .01). Across subgroups, multiple injection site options, small/on par needle, and price made at least two-thirds of clinicians somewhat/much more likely to use a particular LAI, and 63%-82% of clinicians reported being somewhat/much more likely to select an LAI dosed once monthly or less often vs 6%-11% being somewhat/much more likely to select an LAI dosed once every 2 weeks. Overall, results from DECIDE provide insight into the decision-making process of psychiatric clinicians when selecting an LAI and highlight opportunities to help clinicians deliver optimal care for patients with schizophrenia.
This post hoc analysis examined the efficacy of aripiprazole lauroxil (AL) by baseline severity of illness in the double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness study (NCT03345979) in patients with schizophrenia treated with AL every 2 months. Adults with acute schizophrenia were randomized to AL 1064 mg every 2 months or active control (paliperidone palmitate [PP] 156 mg monthly). Based on Clinical Global Impression-Severity scores, baseline severity of illness was categorized as moderate, marked, or severe. Changes from baseline in Positive and Negative Syndrome Scale (PANSS) Total score were assessed at week 25, along with PANSS items related to hostility/excitement. Numbers of patients with activation adverse events (AEs; anxiety, agitation, and insomnia) were also evaluated. Of 99 patients assigned to AL, 31 (31%) were moderately ill at baseline, 54 (55%) were markedly ill, and 14 (14%) were severely ill. With AL treatment, mean ± SE changes from baseline in PANSS Total score at week 25 were -21.1 ± 2.5 (moderately ill; baseline, 87.1), -24.1 ± 1.8 (markedly ill; baseline, 95.3), and -25.6 ± 6.4 (severely ill, baseline, 106.1). Improvements from baseline in PANSS scores related to hostility/excitement items were comparable among severity subgroups. No clear pattern of occurrence of the AEs anxiety, agitation, and insomnia was observed across baseline severity groups. In this post hoc analysis, safety related to activation and efficacy with AL treatment were comparable across baseline severity-of-illness subgroups of patients with schizophrenia.