Quantifying abnormal emotion processing: A novel computational assessment method and application in schizophrenia.

Abnormal emotion processing is a core feature of schizophrenia spectrum disorders (SSDs) that encompasses multiple operations. While deficits in some areas have been well-characterized, we understand less about abnormalities in the emotion processing that happens through language, which is highly relevant for social life. Here, we introduce a novel method using deep learning to estimate emotion processing rapidly from spoken language, testing this approach in male-identified patients with SSDs (n = 37) and healthy controls (n = 51). Using free responses to evocative stimuli, we derived a measure of appropriateness, or "emotional alignment" (EA). We examined psychometric characteristics of EA and its sensitivity to a single-dose challenge of oxytocin, a neuropeptide shown to enhance the salience of socioemotional information in SSDs. Patients showed impaired EA relative to controls, and impairment correlated with poorer social cognitive skill and more severe motivation and pleasure deficits. Adding EA to a logistic regression model with language-based measures of formal thought disorder (FTD) improved classification of patients versus controls. Lastly, oxytocin administration improved EA but not FTD among patients. While additional validation work is needed, these initial results suggest that an automated assay using spoken language may be a promising approach to assess emotion processing in SSDs.

Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

Preliminary evidence that oxytocin does not improve mentalizing in women with schizophrenia.

INTRODUCTION: Mentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. METHODS: We tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. RESULTS: In contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. CONCLUSION: These findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.

Victory is its own reward: oxytocin increases costly competitive behavior in schizophrenia.

BACKGROUND: Aberrant sensitivity to social reward may be an important contributor to abnormal social behavior that is a core feature of schizophrenia. The neuropeptide oxytocin impacts the salience of social information across species, but its effect on social reward in schizophrenia is unknown. METHODS: We used a competitive economic game and computational modeling to examine behavioral dynamics and oxytocin effects on sensitivity to social reward among 39 men with schizophrenia and 54 matched healthy controls. In a randomized, double-blind study, participants received one dose of oxytocin (40 IU) or placebo and completed a 35-trial Auction Game that quantifies preferences for monetary v. social reward. We analyzed bidding behavior using multilevel linear mixed models and reinforcement learning models. RESULTS: Bidding was motivated by preferences for both monetary and social reward in both groups, but bidding dynamics differed: patients initially overbid less compared to controls, and across trials, controls decreased their bids while patients did not. Oxytocin administration was associated with sustained overbidding across trials, particularly in patients. This drug effect was driven by a stronger preference for winning the auction, regardless of monetary consequences. Learning rate and response variability did not differ between groups or drug condition, suggesting that differences in bidding derive primarily from differences in the subjective value of social rewards. CONCLUSIONS: Our findings suggest that schizophrenia is associated with diminished motivation for social reward that may be increased by oxytocin administration.

Oxytocin increases eye gaze in schizophrenia.

Abnormal eye gaze is common in schizophrenia and linked to functional impairment. The hypothalamic neuropeptide oxytocin modulates visual attention to social stimuli, but its effects on eye gaze in schizophrenia are unknown. We examined visual scanning of faces in men with schizophrenia and neurotypical controls to quantify oxytocin effects on eye gaze. In a randomized, double-blind, crossover study, 33 men with schizophrenia and 39 matched controls received one dose of intranasal oxytocin (40 IU) and placebo on separate testing days. Participants viewed 20 color photographs of faces while their gaze patterns were recorded. We tested for differences in fixation time on the eyes between patients and controls as well as oxytocin effects using linear mixed-effects models. We also tested whether attachment style, symptom severity, and anti-dopaminergic medication dosage moderated oxytocin effects. In the placebo condition, patients showed reduced fixation time on the eyes compared to controls. Oxytocin was associated with an increase in fixation time among patients, but a decrease among controls. Higher attachment anxiety and greater symptom severity predicted increased fixation time on the eyes on oxytocin versus placebo. Anti-dopaminergic medication dosage and attachment avoidance did not impact response to oxytocin. Consistent with findings that oxytocin optimizes processing of social stimuli, intranasal oxytocin enhanced eye gaze in men with schizophrenia. Further work is needed to determine whether changes in eye gaze impact social cognition and functional outcomes. Both attachment anxiety and symptom severity predicted oxytocin response, highlighting the importance of examining potential moderators of oxytocin effects in future studies.

Oxytocin effects in schizophrenia: Reconciling mixed findings and moving forward.

Schizophrenia is a severe mental illness that causes major functional impairment. Current pharmacologic treatments are inadequate, particularly for addressing negative and cognitive symptoms of the disorder. Oxytocin, a neuropeptide known to moderate social behaviors, has been investigated as a potential therapeutic for schizophrenia in recent years. Results have been decidedly mixed, leading to controversy regarding oxytocin's utility. In this review, we outline several considerations for interpreting the extant literature and propose a focused agenda for future work that builds on the most compelling findings regarding oxytocin effects in schizophrenia to date. Specifically, we examine underlying causes of heterogeneity in randomized clinical trials (RCTs) conducted thus far and highlight the complexity of the human oxytocin system. We then review evidence of oxytocin's effects on specific deficits in schizophrenia, arguing for further study using objective, precise outcome measures in order to determine whether oxytocin has the potential to improve functional impairment in schizophrenia.

Postpartum depression screening in the pediatric emergency department.

PURPOSE: This study aimed to determine the prevalence of and risk factors for postpartum depression (PPD) in mothers of young infants presenting to the pediatric emergency department (PED). METHODS: This was a prospective, observational study to evaluate the prevalence of PPD in a sample of mothers of young infants presenting to the PED of an urban, tertiary care children's hospital. A convenience sample of mothers with infants younger than 4 months who presented to our urban, tertiary care PED was surveyed in English or Spanish using the Edinburgh Postpartum Depression Scale (EPDS). Demographic information was collected. Members of the study team evaluated and counseled those mothers who screened positive on the EPDS (score ≥ 10). During the PED visit, social work consultation and mental health resources were also offered. Resource use and additional mental health needs were assessed, with a follow-up telephone call 4 weeks after the initial ED presentation. Performance characteristics of a brief, 3-question anxiety subset were compared using a positive EPDS as the reference standard. All study participants were given information about community resources for new mothers. Data were analyzed using t test or Χ (with Yates correction as necessary). RESULTS: A convenience sample of 200 mothers was enrolled; 31 (16%) of these mothers had an EPDS score of 10 or greater. Mothers had a mean age of 27 years (range, 15-41); 45% were first-time mothers; 40% got pediatric care in a state-funded clinic; and 10% were Spanish speaking. There were no statistically significant differences in baseline demographic characteristics of mothers with and without PPD. Mothers who were depressed were more likely to report that they either strongly agreed or agreed with the statement "I feel that my child is always fussy" (P = 0.004). The anxiety subscale produced a sensitivity of 0.87 (95% confidence interval [CI], 0.69-0.96), a specificity of 0.70 (95% CI, 0.63-0.77), and a negative predictive value of 0.97 (95% CI, 0.91-0.99). The majority of participants (92%) reached at follow-up reported improvement in their mood. Fifty percent reported discussing their mood with someone else, although only 33% of these women did so with a medical provider. CONCLUSIONS: Postpartum depression affects a significant number of mothers of young infants who present to the PED for medical care. There are no clear demographic identifiers of these at-risk mothers, making universal screening an advisable approach. Capture of at-risk mothers during PED visits may accelerate connection with mental health resources. Anxiety seems to be a significant contributor. Mothers with PPD often characterize their infants to have a "fussy" temperament. The most appropriate referral for these women in this setting merits further investigation.

Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans.

BACKGROUND: A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. RESULTS: We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. CONCLUSIONS: In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.