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Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia.

Previous research suggests that the Pennebaker writing paradigm may improve physical and psychological health; however, inconsistent findings suggest that it may not be suitable for community dissemination in its current format. This study manipulated writing instructions across groups in order to emphasise putative emotional processes. Three processes were isolated consistent with Cognitive-Behavioral models of trauma: exposure, devaluation, and benefit-finding. Essay content reports, text analysis, distress, arousal, and physiological data demonstrated that participants assigned to different writing instructions responded during and after the writing session in a manner that was consistent with the putative emotion process. The results highlight the potential for the writing paradigm as a research tool for emotional processing.

This article examines the prevalence and prediction of internalising and externalising disorders from temperament and parenting in children aged 4 to 6 years (N = 491). Children were assessed via parent and teacher reports over 14 months and clinical interviews with parents were included at follow-up, along with parent and teacher reports of behavioural and emotional difficulties. Prevalence rates for internalising disorders (8.7%) were higher than for externalising disorders (5.8%), and internalising rates were similar to that found for older children in the same city. Accuracy of prediction of disorders, as well as overall behavioural and emotional difficulties, was low to moderate, and externalising problems were better predicted than internalising problems. The results highlight that while psychological disorders can be predicted from measures of temperament in infancy, the accuracy is too low to recommend these children receive selective prevention and treatment programs.

BackgroundBetween 30 and 60% of adults with unipolar or bipolar disorders exhibit impairments across multiple domains. However, little is known about impaired functioning in youth with mood disorders.AimsTo examine the prevalence of objective, subjective and observer-rated disability in a large, representative sample of young people with a primary mood disorder.MethodIndividuals aged 16–25 years presenting to youth mental health services for the first time with a primary mood disorder participated in a systematic diagnostic and clinical assessment. Impairment was assessed using objective (unemployment or disability payments), observer- (Social and Occupational Functioning Assessment Scale; SOFAS) and self-rated measures (role functioning according to the Brief Disability Questionnaire).ResultsOf 1241 participants (83% unipolar; 56% female), at least 30% were functionally impaired on the objective, self-rated and/or observer-rated measures, with 16% impaired according to all three criteria. Even when current distress levels were taken into account, daily use of cannabis and/or nicotine were significantly associated with impairment, with odds ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders were related to lower SOFAS scores (OR = 2–5).ConclusionsLevels of disability were significant, even in those presenting for mental healthcare for the first time. Functional impairment did not differ between unipolar and bipolar cases, but some evidence suggested that females with bipolar disorder were particularly disabled. The prevalence of comorbid disorders (50%) and polysubstance use (28%) and their association with disability indicate that more meaningful indicators of mood episode outcomes should focus on functional rather than symptom-specific measures. The association between functioning and nicotine use requires further exploration.

Accumulating evidence demonstrates the important role of oxytocin (OT) in the modulation of social cognition and behavior. This has led many to suggest that the intranasal administration of OT may benefit psychiatric disorders characterized by social dysfunction, such as autism spectrum disorders and schizophrenia. Here, we review nasal anatomy and OT pathways to central and peripheral destinations, along with the impact of OT delivery to these destinations on social behavior and cognition. The primary goal of this review is to describe how these identified pathways may contribute to mechanisms of OT action on social cognition and behavior (that is, modulation of social information processing, anxiolytic effects, increases in approach-behaviors). We propose a two-level model involving three pathways to account for responses observed in both social cognition and behavior after intranasal OT administration and suggest avenues for future research to advance this research field.

Research suggests that anxiety is maintained by an attentional bias to threat, and a growing base of evidence suggests that anxiety may additionally be associated with the deficient attentional processing of positive stimuli. The present study sought to examine whether such anxiety-linked attentional biases were associated with either stimulus driven or attentional control mechanisms of attentional selectivity. High and low trait anxious participants completed an emotional variant of an antisaccade task, in which they were required to prosaccade towards, or antisaccade away from a positive, neutral or threat stimulus, while eye movements were recorded. While low anxious participants were found to be slower to saccade in response to positive stimuli, irrespectively of whether a pro- or antisaccade was required, such a bias was absent in high anxious individuals. Analysis of erroneous antisaccades further revealed at trend level, that anxiety was associated with reduced peak velocity in response to threat. The findings suggest that anxiety is associated with the aberrant processing of positive stimuli, and greater compensatory efforts in the inhibition of threat. The findings further highlight the relevance of considering saccade peak velocity in the assessment of anxiety-linked attentional processing.

Background Arginine vasopressin (AVP) has a complex but crucial role in social behavior. In nonhuman mammals it facilitates social recognition and bonding while also promoting defensive, aggressive, and territorial behaviors. There has been little research in humans exploring its effect on social cognition, including the encoding of social memories. Methods In a double-blind, randomized, placebo-controlled, between-subject design, we administered AVP (20 IU) or a placebo intranasally to 48 healthy human male volunteers and then presented 54 happy, angry, or neutral human faces. Participants returned the following day to make "remember", "know", or "new" judgments for a mix of 108 new and previously seen faces. Results Participants who were administered AVP were more likely to make know judgments for previously seen happy and angry faces in comparison with neutral human faces. Arginine vasopressin did not influence judgments for faces that had not been presented previously. Conclusions Administration of AVP to male humans enhances the encoding of both happy and angry social information to make this more memorable. Results suggest that AVP could facilitate both bonding and aggressive related behaviors in humans by enhancing the encoding of positive and negative social cues within everyday interactions.

Background A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. Methods In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger's Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. Results In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. Conclusions This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders.

In the field of clinical research, there is growing interest in the use of eye tracking to provide insights into aberrant styles of information processing associated with a variety of mental illnesses. In particular, research into cognitive factors which maintain and exacerbate social anxiety disorder (SAD) has seen an increase in eye-tracking-based studies. A strong base of literature suggests that biased processing during early attentional stages of information processing is a critical factor in understanding SAD. Given that eye tracking may provide a relatively direct and continuous measure of visual attention, a growing number of studies have incorporated eye movement-based measures in order to assess biased attentional processing. A further capability of eye tracking is its capacity to assess visual attention online during realistic simulations. However, such a capability has been under-utilized in clinical research. The present manuscript outlines a novel experimental design which uses eye tracking during a public speaking simulation. This task seeks to elucidate the mechanisms of attentional bias that characterize social anxiety disorder, as assessment of such biases may potentially provide clinical utility as a marker for SAD and treatment response. Details of the eye movement (EM) measures of attentional bias are described.

The Transitions Study was designed to establish a cohort of young people (12-25 years) seeking help for mental health problems, in order to longitudinally explore and refine a clinical staging model of the development and progression of mental disorders. This paper presents the baseline demographic and clinical characteristics of the cohort, particularly the nature and severity of psychopathology.All eligible young people attending one of four headspace clinical services were invited to participate, and completed a battery of self-report and interviewer-administered measures of psychopathology and functional impairment at baseline, which will be repeated at the annual follow up.Of 1615 eligible clients, 802 young people (66% women; mean age = 18.3 years) consented to participate and completed baseline assessments (participation rate = 50%). The severity of mental health problems varied, with 51% meeting the criteria for probable caseness related to generalized anxiety, 45% presenting with moderate to severe depressive symptoms and over a third experiencing subthreshold psychotic symptomatology. Disordered eating (32%) and problematic tobacco (56%), cannabis (30%) and alcohol (38%) use also affected a significant proportion. Overall, 39% of the cohort were classed as being functionally impaired at baseline.The Transitions Study recruited a heterogeneous cohort at baseline in relation to the nature and severity of mental health problems and levels of functional impairment. The variation in clinical presentations within the cohort, from mild, through moderate to severe levels of psychopathology and impairment, increases the likelihood of the Transitions Study ultimately being able to achieve its aims of empirically testing a clinical staging model for mental disorders.

The role of non-diagnostic features in the pathophysiology of autism spectrum disorders (ASDs) is unclear. Increasing evidence suggests immune system alterations in ASD may be implicated in the severity of behavioral impairment and other developmental outcomes. The primary objective of this meta-analysis was to investigate if there is a characteristic abnormal cytokine profile in ASD compared with healthy controls (HCs). We identified relevant studies following a search of MEDLINE, EMBASE, PsycINFO, Web of Knowledge and Scopus. A meta-analysis was performed on studies comparing plasma and serum concentrations of cytokines in unmedicated participants with ASD and HCs. Results were reported according to PRISMA statement. Seventeen studies with a total sample size of 743 participants with ASD and 592 HC were included in the analysis. Nineteen cytokines were assessed. Concentrations of interleukin (IL)-1beta (P

Background In nonhuman mammals, oxytocin has a critical role in peer recognition and social approach behavior. In humans, oxytocin has been found to enhance trust and the ability to interpret the emotions of others. It has been suggested that oxytocin may enhance facial processing by increasing focus on the eye region of human faces. Methods In a double-blind, randomized, placebo-controlled, between-subject design, we tracked the eye movements of 52 healthy male volunteers who were presented with 24 neutral human faces after intranasal administration of 24 IU oxytocin or placebo. Results Participants given oxytocin showed an increased number of fixations and total gaze time toward the eye region compared with placebo participants. Conclusions Oxytocin increases gaze specifically toward the eye region of human faces. This may be one mechanism by which oxytocin enhances emotion recognition, interpersonal communication, and social approach behavior in humans. Findings suggest a possible role for oxytocin in the treatment of disorders characterized by eye-gaze avoidance and facial processing deficits.

Background Distress and/or dysfunction are well established as key reasons for help-seeking. We explore the characteristics of groups defined by high or low distress or disability in young people with unipolar depression (UP) or bipolar disorder (BD). Methods Individuals aged 12 to 25 years presenting to youth mental health services for the first time with a primary diagnosis of UP or BD were assessed using the Kessler Psychological Distress Scale (Kessler-10) and the Work and Social Adjustment Scale (WSAS). Four groups with high or low distress or impairment were defined (according to scores above or below the group medians for the Kessler-10 and WSAS). Multinomial logistic regression (MNLR) was used to examine how cases with high levels of distress and disability (reference group) differed from the other three groups. Results and discussion The sample comprised 1,746 cases (90% UP, 56% female) with a median age of 17.5 years. Median scores on the Kessler-10 and WSAS were both high (30 and 20, respectively) and were significantly inter-correlated (r = 0.62); the high impairment/distress group was the largest sub-group (39% of cases). The MNLR analysis demonstrated that younger age was associated with lower impairment groups (irrespective of distress level), whilst male gender was associated with lower distress (irrespective of impairment). Compared to the low impairment/distress cases, the high impairment/distress group was significantly more likely to use cannabis and/or alcohol. Age, substance use and possibly gender are probably better predictors of distress/impairment sub-group than mood disorder sub-type in youth.

Background: Impaired emotion recognition in dementia is associated with increased patient agitation, behavior management difficulties, and caregiver burden. Emerging evidence supports the presence of very early emotion recognition difficulties in mild cognitive impairment (MCI); however, the relationship between these impairments and psychosocial measures is not yet explored. Methods: Emotion recognition abilities of 27 patients with nonamnestic MCI (naMCI), 29 patients with amnestic MCI (aMCI), and 22 control participants were assessed. Self-report measures assessed patient functional disability, while informants rated the degree of burden they experienced. Results: Difficulties in recognizing anger was evident in the amnestic subtype. Although both the patient groups reported greater social functioning disability, compared with the controls, a relationship between social dysfunction and anger recognition was evident only for patients with naMCI. A significant association was found between burden and anger recognition in patients with aMCI. Conclusions: Impaired emotion recognition abilities impact MCI subtypes differentially. Interventions targeted at patients with MCI, and caregivers are warranted.

Many studies have highlighted the potential of oxytocin (OT) to enhance facial affect recognition in healthy humans. However, inconsistencies have emerged with regard to the influence of OT on the recognition of specific emotional expressions (happy, angry, fear, surprise, disgust, and sadness). In this study, we conducted a meta-analysis of seven studies comprising 381 research participants (71 females) examining responses to the basic emotion types to assess whether OT enhances the recognition of emotion from human faces and whether this was influenced by the emotion expression and exposure time of the face. Results showed that intranasal OT administration enhances emotion recognition of faces overall, with a Hedges g effect size of 0.29. When analysis was restricted to facial expression types, significant effects of OT on recognition accuracy were specifically found for the recognition of happy and fear faces. We also found that effect sizes increased to moderate when exposure time of the photograph was restricted to early phase recognition (300 ms). The results of the meta-analysis further suggest that OT has potential as a treatment to improve the recognition of emotion in faces, allowing individuals to improve their insight into the intentions, desires, and mental states of others.

Background Clinical staging of mental disorders proposes that individuals can be assessed at various sub-syndromal and later developed phases of illness. As an adjunctive rating, it may complement traditional diagnostic silo-based approaches. In this study, we sought to determine the relationships between clinical stage and neuropsychological profile in young persons presenting to youth-focused mental health services. Methods Neuropsychological testing of 194 help-seeking young people (mean age 22.6 years, 52% female) and 50 healthy controls. Clinical staging rated 94 persons as having an ‘attenuated syndrome’ (stage 1b) and 100 with a discrete or persistent disorder (stage 2/3). Results The discrete disorder group (stage 2/3) showed the most impaired neuropsychological profile, with the earlier stage (1b) group showing an intermediate profile, compared to controls. Greatest impairments were seen in verbal memory and executive functioning. To address potential confounds created by ‘diagnosis’, profiles for those with a mood syndrome or disorder but not psychosis were also examined and the neuropsychological impairments for the stage 2/3 group remained. Conclusions The degree of neuropsychological impairment in young persons with mental disorders appears to discriminate those with attenuated syndromes from those with a discrete disorder, independent of diagnostic status and current symptoms. Our findings suggest that neuropsychological assessment is a critical aspect of clinical evaluation of young patients at the early stages of a major psychiatric illness.

Cumulative evidence over the last decade indicates that intranasally administered oxytocin (OT) has a major impact on social behavior and cognition. In parallel, researchers have also highlighted the effects of OT on cardiovascular (CV) and autonomic nervous system (ANS) regulation. Taken at face value, these two streams of research appear largely unrelated. However, another line of evidence highlights a key role for autonomic cardiac control in social behavior and cognition. In this review, we suggest that autonomic cardiac control may moderate the relationship between OT and social behavior. We also highlight the importance of autonomic cardiac control in psychiatric disorders of social dysfunction and suggest that heart rate variability (HRV)—an index of autonomic cardiac control—may play a key role in patient response in treatment trials of OT.

BackgroundPolyvagal theory emphasizes that autonomic nervous system functioning plays a key role in social behavior and emotion. The theory predicts that psychiatric disorders of social dysfunction are associated with reduced heart rate variability, an index of autonomic control, as well as social inhibition and avoidance. The purpose of this study was to examine whether heart rate variability was reduced in treatment-seeking patients diagnosed with social anxiety disorder, a disorder characterized by social fear and avoidance.MethodsSocial anxiety patients (n = 53) were recruited prior to receiving psychological therapy. Healthy volunteers were recruited through the University of Sydney and the general community and were matched by gender and age (n = 53). Heart rate variability was assessed during a five-minute recording at rest, with participants completing a range of self-report clinical symptom measures.ResultsCompared to controls, participants with social anxiety exhibited significant reductions across a number of heart rate variability measures. Reductions in heart rate variability were observed in females with social anxiety, compared to female controls, and in patients taking psychotropic medication compared to non-medicated patients. Finally, within the clinical group, we observed significant associations between reduced heart rate variability and increased social interaction anxiety, psychological distress, and harmful alcohol use.ConclusionsThe results of this study confirm that social anxiety disorder is associated with reduced heart rate variability. Resting state heart rate variability may therefore be considered a marker for social approach-related motivation and capacity for social engagement. Additionally, heart rate variability may provide a useful biomarker to explain underlying difficulties with social approach, impaired stress regulation, and behavioral inhibition, especially in disorders associated with significant impairments in these domains.

International audience; BACKGROUND: After 30 years of consensus-derived diagnostic categories in mental health, it is time to head in new directions. Those categories placed great emphasis on enhanced reliability and the capacity to identify them via standardized checklists. Although this enhanced epidemiology and health services planning, it failed to link broad diagnostic groupings to underlying pathophysiology or specific treatment response. DISCUSSION: It is time to adopt new goals that prioritize the validation of clinical entities and foster alternative strategies to support those goals. The value of new dimensions (notably clinical staging), that are both clinically relevant and directly related to emerging developmental and neurobiological research, is proposed. A strong emphasis on 'reverse translation' (that is, working back from the clinic to the laboratory) underpins these novel approaches. However, it relies on using diagnostic groupings that already have strong evidence of links to specific risk factors or patterns of treatment response. SUMMARY: The strategies described abandon the historical divides between clinical neurology, psychiatry and psychology and adopt the promotion of pathways to illness models.

Background Past research has highlighted an important role of the autonomic nervous system in alcohol dependence and capacity for self-regulation. While previous studies have examined alcohol dependent inpatients, it remains unclear whether resting-state HRV, a potential psychophysiological marker of ones capacity for self-regulation, is related to craving in patients who currently consume alcohol. Thus, the aim of the present study was to determine whether HRV predicts alcohol craving in dependent individuals in the community. Methods Resting-state HRV and alcohol craving, as indexed by the obsessive compulsive drinking scale, were assessed in 26 alcohol dependent outpatients. Results Results supported hypotheses indicating that HRV accounts for an additional 12.1% of the variance in craving after controlling for age, anxiety and levels of alcohol consumption. Here we show for the first time that resting-state HRV predicts craving in alcohol dependent outpatients. Conclusion Results provide important new evidence for a role of the autonomic nervous system in the maintenance of dependence disorders.

Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = −.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies.

Background Reducing suicidal behaviour is a major public health goal. Expanding access to care has been identified as a key strategy. In Australia, a national network of primary-care based services (headspace) has been established for young people with mental ill-health. This study determines the socio-demographic, psychopathological and illness-stage correlates of suicidal ideation in young persons attending headspace services. Methods Suicidal ideation was recorded using the specific suicide item of the Hamilton Depression Rating Scale (HDRS) in a cohort of subjects aged 12-30 years (N = 494) attending headspace services. Results Of the 494 young persons assessed, 32% (158/494) had a positive response to any level of the HDRS suicide item, consisting of 16% (77/494) reporting that life was not worth living and a further 16% (81/494) reported thoughts of death or suicidal ideation. Young women (19%; 94/494) were more likely to report any positive response as compared with young men (13%; 64/494) [χ2(2,494) = 13.6, p 2(1,347) = 0.0, p = 0.87). However, more serious levels of suicidal ideation were more common in those with depressive disorders or later stages of illness. In multivariate analyses, the major predictors of the degree of suicidal ideation were increasing levels of clinician-rated depressive symptoms (beta = 0.595, p Conclusions Feelings that life is not worth living, thoughts of death or suicidal ideation are common in young people seeking mental health care. These at-risk cognitions are evident before many of these individuals develop severe or persistent mental disorders. Thoughts of death or suicidal ideation may well need to be a primary intervention target in these young people.

Epidemiological literature indicates that the relationship between alcohol consumption and health outcomes reflects a J-shaped curve such that moderate alcohol consumption confers a protective effect in comparison to abstinence, while heavy consumption is associated with poorer health. While heart rate variability (HRV) may underpin the relationship between drinking and poor health in heavy drinkers, it is unclear whether HRV is increased in moderate, habitual drinkers relative to nonhabitual drinkers. HRV and drinking habits were assessed in 47 volunteers. Results supported hypotheses suggesting that moderate, habitual drinking increases HRV. Although not supported by a significant interaction between drinking group and sex, planned follow-up analysis also revealed that these findings may be specific to males. Regardless, results highlight HRV as a candidate mechanism for the findings reported in the epidemiological literature.

article i nfo Emotion Recognition Depression Anxiety Previous research has suggested that psychotic symptoms are associated with impairments in social cogni- tion. However, there is limited research evaluating this association in the context of younger patients with a broad range of mental health problems. In the present study, we evaluated social cognitive performance in 115 treatment-seeking participants who presented to a youth mental health service with affective or psy- chotic disturbances. Participants completed symptom severity measures, a social cognition task (the Reading the Mind in the Eyes Test (RMET)), and a standardised battery of neuropsychological tests. Analyses based on diagnostic groups showed that patients with psychotic illnesses (n = 23) showed impaired performance on the RMET compared to patients with primarily bipolar (n = 40) and depressive illnesses (n = 52). Perfor- mance on the RMET was negatively correlated with positive and negative psychotic symptoms, but not affec- tive and anxiety symptoms. Performance on the RMET also was the strongest concurrent predictor of positive psychotic symptoms in a regression model that also included predicted intelligence, demographic variables, and neurocognition. RMET performance did not, however, predict negative symptoms above tests of sustained attention and verbal learning, nor was performance associated with any other symptoms of mental illness. Social cognitive impairments may provide a valuable marker for the presence of positive psychotic symptoms in young people with mental illness. Additionally, these impairments may have a role in the aetiology and maintenance of psychotic symptoms. Research is now needed to establish the nature of the re- lationship between social cognition and psychotic symptoms across different facets of social cognition. Re- search is also needed to investigate whether targeted social cognition treatments reduce risk for the development of positive psychotic symptoms.

A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans.

Although the use of illness-staging models in clinical medicine has proved particularly useful, the concept has not been widely applied in mental health. Here, we apply a clinical staging framework to a population of help-seeking young people presenting with social anxiety. The goal was to provide a detailed description of common clinical stage of those presenting for treatment of social anxiety, and to delineate the associations between symptom type, severity and clinical stage.The results of a structured clinical interview along with background clinical information formed the basis for consensus-derived decisions regarding clinical stage. Subjects also completed self-report measures to assess anxiety and depressive symptoms. Comparisons were conducted largely between those subjects who were considered to have reached a critical clinical threshold for discrete or progressive disorders (i.e., those staged at two and beyond) and those with 'attenuated syndromes' (stage 1b - 69% of subjects).One hundred forty-three subjects (63% male, mean age = 22.1 years) were clinically assessed prior to entry into active treatment programmes. Subjects assigned to stage two or above reported more psychological distress, higher depression scores and more alcohol use. However, these subjects did not report more severe anxiety symptoms. A higher incidence of substance misuse was a significant feature of those in later clinical stages.The study suggests that those who present with social anxiety are characterized by a broad range of symptom severity, with a small, though significant proportion representing individuals whose mental health problems have already progressed to a stage characterized by greater co-morbidity and risk of chronicity. Our data specifically suggest that depressive symptoms and substance abuse/dependence may differentiate those in earlier and later clinical stages.

The study aims to apply clinical staging to young people who present for mental health care; to describe the demographic features, patterns of psychological symptoms, disability correlates and clinical stages of those young people; and to report longitudinal estimates of progression from less to more severe stages.The study uses cross-sectional and longitudinal assessments of young people managed in specialized youth clinics. On the basis of clinical records, subjects were assigned to a specific clinical 'stage' (i.e. 'help-seeking', 'attenuated syndrome', 'discrete disorder' or 'persistent or recurrent illness').Young people (n = 209, mean age = 19.9 years (range = 12-30 years), 48% female) were selected from a broader cohort of n = 1483 subjects. Ten percent were assigned to the earliest 'help-seeking' stage, 54% to the 'attenuated syndrome' stage, 25% to the 'discrete disorder' stage and 11% to the later 'persistent or recurrent illness' stage. The interrater reliability of independent ratings at baseline was acceptable (κ = 0.71). Subjects assigned to the 'attenuated syndrome' stage reported symptom and disability scores that were similar to those assigned to later stages. Longitudinally (median = 48 weeks), transition to later clinical stages were 11% of the 'help-seeking', 19% of the 'attenuated syndrome' and 33% of the 'discrete disorder' groups.Among young people presenting for mental health care, most are clinically staged as having 'attenuated syndromes'. Despite access to specialized treatment, a significant number progress to more severe or persistent disorders.

Research in animals and humans suggests a role of oxytocin in social approach to strangers. We tested this by introducing undergraduate students to opposite-gendered strangers, with each member of the pair having taken either oxytocin or placebo. One hundred and four undergraduate students were paired up and engaged in a face-to-face conversation structured with a series of intimate topics for discussion. We found that oxytocin increased conversational intimacy in female but not male participants, but that this was matched with compensatory decreases in eye-contact (relative to placebo). Argyle and Dean (1965) conceptualise intimacy as a function of physical distance, eye-contact, and conversational intimacy, such that equilibrium is maintained when increases in one domain are matched by compensatory decreases in another domain. Based on this notion, our results suggest that oxytocin does not facilitate social approach by increasing the intimacy equilibrium between two strangers.

To facilitate early intervention, there is a need to distinguish unipolar versus bipolar illness trajectories in adolescents and young adults with adult-type mood disorders.Detailed clinical and neuropsychological evaluation of 308 young persons (aged 12 to 30 years) with moderately severe unipolar and bipolar affective disorders.Almost 30% (90/308) of young people (mean age=19.4±4.4yr) presenting for care with affective disorders met criteria for a bipolar-type syndrome (26% with bipolar I). Subjects with bipolar- and unipolar-type syndromes were of similar age (19.8 vs. 19.2yr) and reported comparable ages of onset (14.5 vs. 14.3yr). Clinically, those subjects with unipolar and bipolar-type disorders reported similar levels of psychological distress, depressive symptoms, current role impairment, neuropsychological dysfunction and alcohol or other substance misuse. Subjects with unipolar disorders reported more social anxiety (p0.01). Subjects with bipolar disorders were more likely to report a family history of bipolar (21% vs. 11%; [χ(2)=4.0, p.05]) or psychotic (19% vs. 9%; [χ(2)=5.5, p.05]), or substance misuse (35% vs. 23%; [χ(2)=3.9, p.05]), but not depressive (48% vs. 53%; χ(2)=0.3, p=.582]) disorders.Young subjects with bipolar disorders were best discriminated by a family history of bipolar, psychotic or substance use disorders. Early in the course of illness, clinical features of depression, or neuropsychological function, do not readily differentiate the two illness trajectories.

Context Oxytocin (OT) plays a key regulatory role in human social behaviour. While prior studies have examined the effects of OT on observable social behaviours, studies have seldom examined the effects of OT on psychophysiological markers such as heart rate variability (HRV), which provides an index of individual’s motivation for social behaviour. Furthermore, no studies have examined the impact of OT on HRV under resting conditions, which provides an index of maximal capacity for social engagement. Objective To examine the effects of OT on HRV measures in healthy male participants while at rest. OT was hypothesised to increase HRV, compared to placebo, and that the effects would be greatest for a non-linear measure of HRV (the detrended fluctuation scaling exponent). Methods Twenty-one male participants were recruited for this study. Participants were non-smokers, not on any medications and reported no history of psychiatric illness, neurological disorder, or any other serious medical condition (e.g. diabetes, cardiovascular disease). The study employed a randomised, placebo-controlled, within-subject, crossover, experimental design. Main Outcome Measures HRV was calculated from electrocardiography under a standardized, 10-minute, resting state condition. Results As hypothesised, OT increased HRV and these effects were largest using the detrended fluctuation scaling exponent, a non-linear measure. These changes were observed in the absence of any change in state mood, as measured by the profile of mood states. Importantly, participants were unable to correctly guess which treatment they had been assigned at either of the two assessments. Conclusions Together with the broader literature on OT and HRV, findings suggest that acute administration of OT may facilitate a fundamental psychophysiological feature of social behaviour, increasing capacity for social engagement. Findings also suggest that HRV changes may provide a novel biomarker of response to OT nasal spray that can be incorporated into research on response to treatment.

Purpose Adults who stutter are at significant risk of developing social phobia. Cognitive theorists argue that a critical factor maintaining social anxiety is avoidance of social information. This avoidance may impair access to positive feedback from social encounters that could disconfirm fears and negative beliefs. Adults who stutter are known to engage in avoidance behaviours, and may neglect positive social information. This study investigated the gaze behaviour of adults who stutter whilst giving a speech. Method 16 adults who stutter and 16 matched controls delivered a 3-min speech to a television display of a pre-recorded lecture theatre audience. Participants were told the audience was watching them live from another room. Audience members were trained to display positive, negative and neutral expressions. Participant eye movement was recorded with an eye-tracker. Results There was a significant difference between the stuttering and control participants for fixation duration and fixation count towards an audience display. In particular, the stuttering participants, compared to controls, looked for shorter time at positive audience members than at negative and neutral audience members and the background. Conclusions Adults who stutter may neglect positive social cues within social situations that could serve to disconfirm negative beliefs and fears. Educational objectives: The reader will be able to: (a) describe the nature of anxiety experienced by adults who stutter; (b) identify the most common anxiety condition among adults who stutter; (c) understand how information processing biases and the use of safety behaviours contribute to the maintenance of social anxiety; (d) describe how avoiding social information may contribute to the maintenance of social anxiety in people who stutter; and (e) describe the clinical implications of avoidance of social information in people who stutter.

The past eight years of research has demonstrated that oxytocin nasal spray has a significant impact on human social cognition. The aim of this review is to provide critical comment on the literature using an information-processing framework. We provide a summary of fundamental assumptions of information-processing models and highlight an impressive range of consistent findings that demonstrate the impact of oxytocin nasal spray on social information processing. These findings include that oxytocin nasal spray improves the early conceptual detection of affect from social cues and improves the accurate appraisal of affect from social cues at elaborate and strategic levels of processing. There is some evidence that these effects may be particularly powerful for positive social cues. This review comments on inconsistent results that have been reported. We argue that such inconsistencies can, in part, be explained by variability across experiments in the degree to which potential extraneous confounds have been controlled, the different methods upon which studies assessed cognition, and the extent to which the focus of investigation has been on group-based outcomes. Finally, we argue that sound cognitive experimental methods can provide powerful tools to identify markers of response to oxytocin nasal spray that can be integrated into more complex circuitry models. The identification of robust markers has particular value in predicting behavioral and therapeutic response to intervention. This should now be a major focus for future research. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Individuals differ in the extent to which their vulnerability to anxiety is reduced by psychological therapy. However, the cognitive basis for such individual differences is still poorly understood. To test a cognitive account of differences in anxiety reduction in response to treatment, the present study examined individuals undergoing group therapy for social anxiety disorder. We assessed whether differences in their readiness to adopt selective attentional processing in response to an experimental contingency predicted positive changes in a range of anxiety measures in response to treatment. Findings were consistent with the position that readiness to alter attentional processing bias may underpin individual differences in the tendency to respond to positive experiential conditions, such as group therapy, by reducing anxiety vulnerability.

The mammalian neuropeptide oxytocin has well-characterized effects in facilitating prosocial and affiliative behavior. Additionally, oxytocin decreases physiological and behavioral responses to social stress. In the present study we investigated the effects of oxytocin on cognitive appraisals after a naturalistic social stress task in healthy male students. In a randomized, double-blind, placebo-controlled trial, 48 participants self-administered either an oxytocin or placebo nasal spray and, following a wait period, completed an impromptu speech task. Eye gaze to a pre-recorded video of an audience displayed during the task was simultaneously collected. After the speech, participants completed questionnaires assessing negative cognitive beliefs about speech performance. Whilst there was no overall effect of oxytocin compared to placebo on either eye gaze or questionnaire measures, there were significant positive correlations between trait levels of anxiety and negative self-appraisals following the speech. Exploratory analyses revealed that whilst higher trait anxiety was associated with increasingly poorer perceptions of speech performance in the placebo group, this relationship was not found in participants administered oxytocin. These results provide preliminary evidence to suggest that oxytocin may reduce negative cognitive self-appraisals in high trait anxious males. It adds to a growing body of evidence that oxytocin seems to attenuate negative cognitive responses to stress in anxious individuals.

Since hypnosis was popularly recognized in the nineteenth century, the phenomenon of hypnotizability has remained poorly understood. The capacity to increase hypnotizability has important implications because it may increase the number of people who can benefit from hypnotic interventions for psychological and medical conditions. Current theories emphasize that rapport between hypnotist and subject is pivotal to motivate the respondent to engage in strategies that allows them to suspend reality and respond to suggestions. The neuropeptide oxytocin is implicated in social bonding, and enhances a range of social behaviors in animals and humans. This study tested the proposal that oxytocin administration, which enhances social bonding in humans, may enhance hypnotic responding by administering intranasal spray of oxytocin or placebo prior to hypnosis in 40 low hypnotizable male subjects. When low hypnotizable individuals were administered oxytocin via nasal spray, their level of hypnotic responding increased significantly compared to hypnotic responding levels prior to oxytocin administration. This is the first demonstration of a neurochemical basis for hypnotic responding, and points to a potential neural mechanism to explain hypnotizability.

Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.

The hormone and neuropeptide oxytocin is believed to buffer against social stress and reduce social-threat perception. We employed a widely used ostracism paradigm, Cyberball, to investigate whether oxytocin ameliorated the acute behavioral and affective consequences of social rejection. In a double-blind, randomized, between-subjects design, 74 healthy male and female participants were administered intranasal oxytocin or placebo and subsequently ostracized or included during this virtual ball-tossing game. Ostracized participants reported negative affective and attachment-related reactions, as well as a significant motivational change in increased desire to be involved in the game; these effects were not influenced by oxytocin. Intranasal oxytocin did, however, increase included participants' desire to play again with the same participants, suggesting oxytocin enhanced desire for future social engagement following inclusion. These findings are argued to provide evidence that the effects of oxytocin in promoting social approach behavior may be context specific and sensitive to positive social cues. The results suggest that in an explicitly aversive context, oxytocin does not buffer against the immediate impact of blunt social rejection.

Background Generalised anxiety disorder (GAD) is a high prevalence, chronic psychiatric disorder which commonly presents early in the lifespan. Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder (PTSD), panic disorder, social phobia and depression. However, to date, there is little evidence for the effectiveness of e-health applications in adult GAD. There are no studies which have directly compared e-health applications with recognised evidence-based medication. This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo. Methods/Design 120 community-dwelling participants, aged 18-30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll. They will be randomly allocated to one of three conditions: (i) an online treatment program for GAD, E-couch (ii) pharmacological treatment with a selective serotonin re-uptake inhibitor (SSRI), sertraline (a fixed-flexible dose of 25-100 mg/day) or (iii) an attention control placebo, HealthWatch. The treatment program will be completed over a 10 week period with a 12 month follow-up. Discussion As of February 2010, there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults. Similarly to date, this will be the first trial to compare an e-health intervention with a pharmacological treatment. Trial Registration Current Controlled Trials ISRCTN76298775

To the Editor:We read with much interest the article by Shamay-Tsooryandcolleagues,whichreportedthatoxytocinincreasesenvy and gloating (1), and recent correspondencedebating whether oxytocin is engaged in positive prosocialbehavior (2) or increases the salience of social behaviors moregenerally (3). Shamay-Tsoory

The neuropeptide oxytocin (OT) has a crucial role in social behavior (Bartz & Hollander, 2006). Oxytocin improves trust (Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005), emotion perception (Domes, Henrichs, Michel, Berger, & Herpertz, 2007), eye-gaze (Guastella, Mitchell, & Dadds, 2008), and the encoding of happy faces (Guastella, Mitchell, & Mathews, 2008). However, the mechanisms underlying these observations are not fully understood. One explanation, from evolutionarybiological perspectives (Heinrichs, Meinlschmidt, Wippich, Ehlert, & Hellhammer, 2004), is that OT selectively facilitates the processing of positive social cues that are important for bonding and reproductive behavior. This study is the first to investigate whether OT produces a selective recognition advantage for identifying such positive social stimuli. We used a constructive recognition task in which a gradually disappearing mask slowly reveals the target stimulus. This methodology is ideally suited to assess top-down influences on cognition and was successfully used to demonstrate mood congruency effects (Fiedler, Nickel, Muehlfriedel, & Unkelbach, 2001; Forgas, 1995). We predicted that OT selectively enhances the recognition and categorization speed of positive sexually-themed and relationship words, but OT should not alter the processing of positive stimuli in general.

Damage to the amygdala produces deficits in the ability to recognize fear due to attentional neglect of other people's eyes. Interestingly, children with high psychopathic traits also show problems recognizing fear; however, the reasons for this are not known. This study tested whether psychopathic traits are associated with reduced attention to the eye region of other people's faces.Adolescent males (N = 100; age mean 12.4 years, SD 2.2) were stratified by psychopathic traits and assessed using a Tobii eye tracker to measure primacy, number, and duration of fixations to the eye and mouth regions of emotional faces presented via the UNSW Facial Emotion Task.High psychopathic traits predicted poor fear recognition (1.21 versus 1.35; p.05) and lower number (1.85 versus 2.51; p.001) and duration (375 versus 620 ms; p.001) of eye fixations, and fewer first foci to the eye region (1.01 versus 2.01; p.001). There were no differences in gaze indices to the mouth region. All indices of gaze to the eye region correlated positively with accurate recognition of fear for the high psychopathy group, especially the number of times that subjects looked at the eyes first (r = .50; p.01).Attention to other people's eyes is reduced in young people with high psychopathic traits, thus accounting for their problems with fear recognition, and is consistent with amygdala dysfunction failing to promote attention to emotional salience in the environment.

Background In nonhuman mammals, oxytocin has a critical role in social recognition and the development of long-term bonds. There has been limited research evaluating effects of oxytocin on the encoding and recognition of faces in humans. Methods In a double-blind, randomized, placebo-controlled, between-subject design, we administered oxytocin (24 IU) or a placebo to 69 healthy human male volunteers and then presented 36 happy, angry, or neutral human faces. Participants returned the following day to make “remember,” “know,” or “new” judgments for a mix of 72 new and previously seen faces. Results Oxytocin-administered participants were more likely to make remember and know judgments for previously seen happy faces compared with angry and neutral human faces. In contrast, oxytocin did not influence judgments for faces that had not been presented previously. Conclusions This study shows that the administration of oxytocin to male humans enhances the encoding of positive social information to make it more memorable. Results suggest that oxytocin could enhance social approach, intimacy, and bonding in male humans by strengthening encoding to make the recall of positive social information more likely.

We report on a controlled trial of three structured writing paradigms that engage the writer with cognitive-behavioural emotion-processes: exposure, devaluation, and benefit-finding. University students (N = 198) wrote once a week for three weeks about their most upsetting experience. The long-term effects of these structured writing procedures were compared to an unstructured emotion writing condition and control. Outcomes indicated that exposure writing sped the reduction of intrusive and avoidant symptoms, while benefit-finding writing increased reports of positive growth. Results suggest the use of these paradigms to study emotion-processing mechanisms and, potentially, in practice to enhance coping in process-specific ways.

Background Pilot research has suggested that D-cycloserine (DCS) enhances treatment outcomes for anxiety disorders when employed as an adjunct to exposure therapy (ET). The aim of this study was to determine whether 50 mg of DCS enhances ET for social anxiety disorder (SAD) according to a comprehensive set of symptom and life impairment measures. Methods In a randomized double-blind placebo-controlled trial, we administered 50 mg of DCS or placebo in combination with ET to 56 participants who met primary diagnosis for SAD. Results Participants administered DCS reported greater improvement on measures of symptom severity, dysfunctional cognitions, and life-impairment from SAD in comparison with placebo-treated participants. Effect sizes were mostly in the medium range. Results also indicated that the amount of adaptive learning about one's ability to give speeches in front of an audience interacted with DCS to enhance treatment outcome. Conclusions This study shows that the administration of DCS before ET enhances treatment outcomes for SAD. Results also provide the first preliminary evidence to suggest that DCS moderates the relationship between a reduction in negative appraisals about one's speech performance and improvement in overall SAD symptoms.

Large placebo responses in many clinical trials limit our capacity to identify effective therapeutics. Although it is often assumed that core behaviors in children with autism spectrum disorders (ASDs) rarely remit spontaneously, there has been limited investigation of the size of the placebo response in relevant clinical trials. These trials also rely on caregiver and clinical observer reports as outcome measures. The objectives of this meta-analysis are to identify the pooled placebo response and the predictors of placebo response in pharmacological and dietary supplement treatment trials for participants with a diagnosis of ASD. Randomized controlled trials (RCTs) in pediatric ASD, conducted between 1980 and August 2014, were identified through a search of Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and clinicaltrials.gov. RCTs of at least 14 days duration, comparing the treatment response for an oral active agent and placebo using at least one of the common outcome measures, were included. Analysis of 25 data sets (1315 participants) revealed a moderate effect size for overall placebo response (Hedges’ g=0.45, 95% confidence interval (0.34–0.56), P

Previous research [Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, et al. Augmentation of exposure therapy for social anxiety disorder with d -cycloserine. Archives of General Psychiatry 2006;63:298–304; Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, et al. Cognitive enhancers as adjuncts to psychotherapy: use of d -cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry 2004;61:1136–44] suggests that d -cycloserine (DCS) facilitates the reduction of clinical fear in humans. We used a well established intervention to evaluate the effectiveness of administering DCS as an adjunct to exposure therapy in a heightened, but sub-clinical, fear population. Over two studies, 100 spider-fearful participants were allocated to DCS or placebo before treatment and were assessed at pre-, immediate post-, and 3.5 weeks post-treatment. Significant treatment effects and return of fear was observed at follow-up, particularly in non-treatment contexts; however, both studies failed to demonstrate any enhancing effects of DCS (50 or 500 mg). DCS did not enhance the reduction of spider fears or the generalisation of treatment of a single session of exposure-based therapy. These results suggest that DCS may not enhance loss of non-clinical levels of fear in human populations.

Objective Youth with mental health problems often have difficulties engaging in education and employment. In Australia, youth mental health services have been widely established with a key aim of improving role functioning; however, there is little knowledge of those who are not engaged in employment, education or training (NEET) and the factors which may influence this. This study aimed to examine NEET status and its correlates in a sample of such youth. Design Cross-sectional data from a longitudinal cohort study. Setting Between January 2011 and August 2012, young people presenting to one of the four primary mental health centres in Sydney or Melbourne were invited to participate. Participants Young adults (N=696) aged between 15 and 25 years (M=19.0, SD=2.8), 68% female, 58% (n=404) attended headspace in Sydney. Measures Individuals ‘Not in any type of Education, Employment or Training’ in the past month were categorised as NEET. Demographic, psychological and clinical factors alongside disability and functioning were assessed using clinical interview and self-report. Results A total of 19% (n=130/696) were NEET. NEETs were more likely to be male, older, have a history of criminal charges, risky cannabis use, higher level of depression, poorer social functioning, greater disability and economic hardship, and a more advanced stage of mental illness than those engaged in education, training or work. Demographics such as postsecondary education, immigrant background and indigenous background, were not significantly associated with NEET status in this sample. Conclusions One in five young people seeking help for mental health problems were not in any form of education, employment and training. The commonly observed risk factors did not appear to influence this association, instead, behavioural factors such as criminal offending and cannabis use appeared to require targeted intervention.