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.

Social acceptance (vs. rejection) is assumed to have widespread positive effects on the recipient; however, ethnic/racial minorities often react negatively to social acceptance by White individuals. One possibility for such reactions might be their lack of trust in the genuineness of White individuals' positive evaluations. Here, we examined the role that oxytocin-a neuropeptide putatively linked to social processes-plays in modulating reactions to acceptance or rejection during interracial interactions. Black participants (N = 103) received intranasal oxytocin or placebo and interacted with a White, same-sex stranger who provided positive or negative social feedback. After positive feedback, participants given oxytocin (vs. placebo) tended to display approach-oriented cardiovascular responses of challenge (vs. threat), exhibited more cooperative behavior, and perceived the partner to have more favorable attitudes toward them after the interaction. Following negative feedback, oxytocin reduced anger suppression. Oxytocin did not modulate testosterone reactivity directly, but our exploratory analysis showed that the less participants suppressed anger during the interaction with their partner, the greater testosterone reactivity they displayed after the interaction. These results survived the correction for multiple testing with a false discovery rate (FDR) of 20%, but not with a rate of 10 or 5%. Discussion centers on the interplay between oxytocin and social context in shaping interracial interactions.

Experiential negative symptoms-including diminished motivation-have a profound impact on functional outcomes in schizophrenia. Animal research suggests that abnormalities in dopaminergic regulation can negatively impact effort exertion, a translational model that has been applied to individuals with schizophrenia. Paradigms that assess effort-based decision making, for example, suggest less likelihood of choosing high effort tasks that are high in probability of success, and this preference varies with negative symptoms and impaired functioning. Although asociality is another well-documented component of experiential negative symptoms, it is unclear whether diminished motivation for monetary reward extends to the social domain. To test this question, the authors designed the Social Vigor Task (SVT)-a measure of effort exertion in the context of live social encouragement. They further examined the effect of oxytocin, a neuropeptide implicated in social behavior, on vigor. Forty-two individuals with schizophrenia and 43 healthy controls completed the SVT twice: once after intranasal administration of saline placebo and again after oxytocin. Both groups showed similar increases in vigor in response to social encouragement, suggesting effort in the social context is spared in schizophrenia. Group differences in the effect of social encouragement on vigor varied by point-based reward rate and trial length. Oxytocin did not increase vigor during social encouragement in either group. Within the schizophrenia group, clinician-rated passive social withdrawal, but not active social avoidance, was negatively associated with vigor. Results suggest that people with schizophrenia show normative levels of effort in the context of social encouragement; low approach motivation, however, relates to lower effort. (PsycINFO Database Record

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.

Background

Photographic stimuli are commonly used to assess cue reactivity in the research and treatment of alcohol use disorder. The stimuli used are often non-standardized, not properly validated, and poorly controlled. There are no previously published, validated, American-relevant sets of alcohol images created in a standardized fashion.

Objectives

We aimed to: 1) make available a standardized, matched set of photographic alcohol and non-alcohol beverage stimuli, 2) establish face validity, the extent to which the stimuli are subjectively viewed as what they are purported to be, and 3) establish construct validity, the degree to which a test measures what it claims to be measuring.

Methods

We produced a standardized set of 36 images consisting of American alcohol and non-alcohol beverages matched for basic color, form, and complexity. A total of 178 participants (95 male, 82 female, 1 genderqueer) rated each image for appetitiveness. An arrow-probe task, in which matched pairs were categorized after being presented for 200 ms, assessed face validity. Criteria for construct validity were met if variation in AUDIT scores were associated with variation in performance on tasks during alcohol image presentation.

Results

Overall, images were categorized with >90% accuracy. Participants' AUDIT scores correlated significantly with alcohol "want" and "like" ratings [r(176) = 0.27, p = <0.001; r(176) = 0.36, p = <0.001] and arrow-probe latency [r(176) = -0.22, p = 0.004], but not with non-alcohol outcomes. Furthermore, appetitive ratings and arrow-probe latency for alcohol, but not non-alcohol, differed significantly for heavy versus light drinkers.

Conclusion

Our image set provides valid and reliable alcohol stimuli for both explicit and implicit tests of cue reactivity. The use of standardized, validated, reliable image sets may improve consistency across research and treatment paradigms.

Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Social cognitive impairments, including theory of mind (ToM), in schizophrenia more strongly predict functional outcomes than psychotic symptoms or nonsocial cognitive deficits. Despite their clinical importance, current medications do not improve these deficits. The current study investigated the hypothesis that oxytocin, a neuropeptide implicated in social behavior, would normalize neural abnormalities in schizophrenia during ToM, and that this normalization would correlate improvement in ToM behavior. In this cross-over, double-blind, and placebo-controlled functional magnetic resonance imaging study, a single dose of 40 IU of oxytocin was administered via nasal spray to male individuals with a schizophrenia spectrum disorder (schizophrenia and schizoaffective disorder, n = 23) and healthy controls (n = 25). Participants completed two ToM tasks in the scanner, the False Belief and Person Description tasks. During both tasks, on placebo day, schizophrenia was associated with reduced accuracy, hypo-activity in the right temporo-parietal junction (rTPJ; extended into the posterior superior temporal sulcus), and hypo-connectivity between the rTPJ and medial prefrontal cortex (mPFC) compared to healthy controls. Oxytocin, relative to placebo, significantly increased accuracy and rTPJ activation for ToM but not control stories in schizophrenia. Furthermore, a significant positive correlation was found between oxytocin induced increases in rTPJ activity and accuracy, indicating that oxytocin improved rTPJ activity in schizophrenia predicted behavioral improvement. Oxytocin also significantly improved connectivity between rTPJ and mPFC in schizophrenia. These findings suggest that rTPJ activity during ToM might be a potential neural target for the treatment of social cognitive deficits in schizophrenia.

Objective

Individuals with schizophrenia demonstrate cognitive, social cognitive, and motivational deficits that contribute to impairment in real-world functioning. In the current study, we investigated the effects of supplementing computerized neurocognitive training with social cognitive exercises, as compared with neurocognitive training alone.

Method

In this ongoing, double-blind, randomized controlled trial of 111 participants with psychosis, we compare the effects of supplementing intensive targeted cognitive training with social cognitive training exercises (TCT + SCT) with the effects of targeted cognitive training alone (TCT-only). Participants were assessed on cognition, symptoms, functional capacity, and functional outcomes, as well as social cognition and measures related to reward processing.

Results

Both treatment groups showed significant improvement in multiple cognitive domains and improvement in functional capacity. However, as predicted, TCT + SCT group participants showed significant improvement in prosody identification and reward processing relative to TCT-only participants.

Conclusions and implications for practice

Our findings indicate that supplementing intensive computerized cognitive training with social cognitive exercises in people with psychosis confers greater benefits in prosody identification and reward processing relative to cognitive training alone, even though both approaches drive significant improvements in cognition and functional capacity. Impairments in both prosody identification and reward processing have been associated with greater negative symptoms and poorer functional outcomes in schizophrenia, raising the possibility that this form of treatment may lead to better long-term outcomes than traditional cognitive training approaches. Follow-up assessments will determine whether results are durable and generalize over time to improvements in symptoms and functioning. (PsycINFO Database Record