Trajectories of suicidal risk among individuals with first-episode psychosis: Relationship to recovery and symptoms.

This study examined trajectories of suicide-risk and their relationship to symptoms, recovery, and quality of life over time. Data was obtained from the Recovery after an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study. 404 individuals with first-episode psychosis (FEP) completed measures of suicide-risk, depression, positive symptoms, recovery, and quality of life at baseline, 6mo, 12mo, 18mo, and 24mo. Latent class analysis was used to identify temporal trajectories of suicide-risk. General linear mixed models for repeated measures were used to examine the relationship between the latent trajectories of suicide-risk and clinical variables. Results identified three latent trajectories of suicide-risk (low-risk, worsening, and improving). The low-risk and improving classes experienced improvements in depression, positive symptoms, quality of life, and recovery over time. The worsening class experienced improvements in positive symptoms and quality of life, but no change in depression or recovery. These results suggest that some individuals with FEP are at risk for persistent depression and worsening suicide-risk during treatment despite experiencing improvements in positive symptoms and quality of life. These findings have important clinical implications, as persistent depression and worsening suicide-risk might be masked by the primary focus on positive symptoms and quality of life in most FEP clinics.

Hierarchical gradients of encoded spatial and sensory information in the neocortex are attenuated by dorsal hippocampal lesions.

During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of spatial and sensorimotor information among cortical cells, and whether hippocampal feedback continues to modify these properties in familiar environments, remains poorly understood. Thus, two-photon microscopy of male and female Thy1-GCaMP6s mice was used to longitudinally image neurons spanning superficial retrosplenial cortex and layers II-Va of primary and secondary motor cortices before and after bilateral dorsal hippocampal lesions. During behaviour on a familiar cued treadmill, the locations of two added obstacles were interchanged to decouple place-tuning from cue-tuning among the position correlated cells with fields at those locations. The subpopulations of place- and cue-tuned cells each formed interareal gradients such that higher-level cortical regions exhibited higher fractions of place cells, whereas lower-level regions exhibited higher fractions of cue cells. Position correlated cells in motor cortex also formed translaminar gradients; cells closer to the cortical surface were more likely to exhibit fields and were more sparsely and precisely tuned than deeper cells. After dorsal hippocampal lesions, a neural representation of the learned environment persisted but retrosplenial cortex exhibited significantly increased cue-tuning and, in motor cortices, both position correlated cell recruitment and population activity at the unstable obstacle locations became more homogeneously elevated across laminae. Altogether, these results support that the hippocampus continues to modulate cortical responses in familiar environments, and the relative impact of top-down feedback obeys hierarchical interareal and interlaminar gradients opposite to the flow of bottom-up sensory inputs.Significance statement During learning, the hippocampus imparts spatial context to memory representations throughout the superficial neocortex. However, the post-learning role of the hippocampus has not been well defined. The results of this study suggest that, during navigation of a familiar environment, the hippocampus continues to link unreliable sensory attributes to a stable contextual framework, effectively updating the learned model of the environment. The results are also consistent with top-down suppression of sensory-evoked activity during behaviour, which varied in strength according to hierarchical proximity to the hippocampus. This effect was abolished by bilateral lesions of the dorsal hippocampus, supporting that the hippocampus plays an ongoing role in propagating context-dependent predictions throughout the cortical hierarchy, a core hypothesis of the predictive coding theoretical framework.

Narrative-Derived Indices of Metacognition among People with Schizophrenia: Associations with Self-Reported and Performance-Based Social Functioning.

Metacognitive functioning-which broadly encompasses the mental processes involved in thinking about the thinking of one's self and the thinking of others-is often impaired among individuals living with schizophrenia and may contribute to difficulties in social and interpersonal functioning. Although the majority of studies assessing metacognition among individuals with schizophrenia use standardized, laboratory-based measurements, an increasing number of studies have measured metacognitive capacity using natural language produced by individuals living with mental illness. At the same time, less is known about how language-derived indices of metacognitive function relate to key social outcomes among people with schizophrenia. The primary objective of this study was to employ a validated language coding system (the Metacognition Assessment Scale, Abbreviated; MAS-A) to assess metacognitive functioning from the spoken life narratives of individuals with schizophrenia (n = 32) and community controls (n = 15). Among individuals with schizophrenia, we also examined the associations between language-derived metacognition and measures of self-reported and performance-based social functioning. Our results suggest that most aspects of metacognition in our sample were not significantly diminished in people with schizophrenia compared to community controls. Unexpectedly, the MAS-A subscale related to one's ability to master psychological difficulties was rated higher among individuals with schizophrenia. Further, our results suggest that among people with schizophrenia, higher metacognitive functioning in the domain of self-reflectivity was associated with poorer self-reported social functioning, while a greater metacognitive awareness of other individuals' minds was associated with better scores on aspects of performance-based social functioning. Collectively, these results underscore the utility of assessing metacognitive functioning via life-story narratives to understand social outcomes and highlight possible aspects of resiliency among individuals who have experienced a serious mental illness.

Identification of Psychosis Risk and Diagnosis of First-Episode Psychosis: Advice for Clinicians.

Early detection of psychotic-spectrum disorders among adolescents and young adults is crucial, as the initial years after psychotic symptom onset encompass a critical period in which psychosocial and pharmacological interventions are most effective. Moreover, clinicians and researchers in recent decades have thoroughly characterized psychosis-risk syndromes, in which youth are experiencing early warning signs indicative of heightened risk for developing a psychotic disorder. These insights have created opportunities for intervention even earlier in the illness course, ideally culminating in the prevention or mitigation of psychosis onset. However, identification and diagnosis of early signs of psychosis can be complex, as clinical presentations are heterogeneous, and psychotic symptoms exist on a continuum. When a young person presents to a clinic, it may be unclear whether they are experiencing common, mild psychotic-like symptoms, early warning signs of psychosis, overt psychotic symptoms, or symptoms better accounted for by a non-psychotic disorder. Therefore, the purpose of this review is to provide a framework for clinicians, including those who treat non-psychotic disorders and those in primary care settings, for guiding identification and diagnosis of early psychosis within the presenting clinic or via referral to a specialty clinic. We first provide descriptions and examples of first-episode psychosis (FEP) and psychosis-risk syndromes, as well as assessment tools used to diagnose these conditions. Next, we provide guidance as to the differential diagnosis of conditions which have phenotypic overlap with psychotic disorders, while considering the possibility of co-occurring symptoms in which case transdiagnostic treatments are encouraged. Finally, we conclude with an overview of early detection screening and outreach campaigns, which should be further optimized to reduce the duration of untreated psychosis among youth.

From grouping and cooperation to menstruation: Spiny mice (Acomys cahirinus) are an emerging mammalian model for sociality and beyond.

While spiny mice are primarily used as a model for Type II diabetes and for studying complex tissue regeneration, they are also an emerging model for a variety of studies examining hormones, behavior, and the brain. We began studying the spiny mouse to take advantage of their highly gregarious phenotype to examine how the brain facilitates large group-living. However, this unique rodent can be readily bred and maintained in the lab and can be used to ask a wide variety of scientific questions. In this brief communication we provide an overview of studies that have used spiny mice for exploring physiology and behavior. Additionally, we describe how the spiny mouse can serve as a useful model for researchers interested in studying precocial development, menstruation, cooperation, and various grouping behaviors. With increasingly available technological advancements for non-traditional organisms, spiny mice are well-positioned to become a valuable organism in the behavioral neuroscience community.

Symptomatic and Functional Outcomes Among Individuals at High Risk for Psychosis Participating in Step-Based Care.

Validated, multicomponent treatments designed to address symptoms and functioning of individuals at clinical high risk for psychosis are currently lacking. The authors report findings of a study with such individuals participating in step-based care-a program designed to provide low-intensity, non-psychosis-specific interventions and advancement to higher-intensity, psychosis-specific interventions only if an individual is not meeting criteria for a clinical response. Among individuals with symptomatic or functional concerns at enrollment, 67% met criteria for a symptomatic response (median time to response=11.1 weeks), and 64% met criteria for a functional response (median time to response=8.9 weeks).

Early life social complexity shapes adult neural processing in the communal spiny mouse Acomys cahirinus.

RATIONALE: Early life social rearing has profound consequences on offspring behavior and resilience. Yet, most studies examining early life development in rodents use species whose young are born immobile and do not produce complex social behavior until later in development. Furthermore, models of rearing under increased social complexity, rather than deprivation, are needed to provide alternative insight into the development of social neural circuitry. OBJECTIVES: To understand precocial offspring social development, we manipulated early life social complexity in the communal spiny mouse Acomys cahirinus and assessed long-term consequences on offspring social behavior, exploration, and neural responses to novel social stimuli. METHODS: Spiny mouse pups were raised in the presence or absence of a non-kin breeding group. Upon adulthood, subjects underwent social interaction tests, an open field test, and a novel object test. Subjects were then exposed to a novel conspecific and novel group and neural responses were quantified via immunohistochemical staining in brain regions associated with social behavior. RESULTS: Early life social experience did not influence behavior in the test battery, but it did influence social processing. In animals exposed to non-kin during development, adult lateral septal neural responses toward a novel conspecific were weaker and hypothalamic neural responses toward a mixed-sex group were stronger. CONCLUSIONS: Communal species may exhibit robust behavioral resilience to the early life social environment. But the early life environment can affect how novel social information is processed in the brain during adulthood, with long-term consequences that are likely to shape their behavioral trajectory.

Metacognitive Skills Training and Computerized Cognitive Remediation among Individuals with First-Episode Psychosis: Influence on Social Cognition.

Background: Metacognitive skills training (MST) is often integrated into cognitive remediation programs for psychosis. Social cognition - the mental processes underlying social perception and behavior - is robustly related to outcomes in psychosis and is increasingly addressed with targeted treatments. Though metacognition and social cognition are related constructs, little is known about how MST may influence social cognition among individuals with psychosis participating in broad-based, non-social cognitive remediation. Methods: Individuals with first-episode psychosis who completed six months of metacognitive remediation (MCR; n=12) were compared to a historical control group who received six months of computerized cognition remediation (CCR; n=10) alone (ClinicalTrials.gov Identifier NCT01570972). Results: Though individuals receiving MCR experienced gains in emotion processing and theory of mind, these changes were not significantly different when compared to individuals receiving CCR. MST did not contribute to social cognitive change in the context of CCR. Discussion: Though MST may be relevant to facilitating social cognitive gains within broader cognitive remediation programs for first-episode psychosis, these benefits are limited and may not exceed those conferred by standard cognitive remediation. Opportunities for investigation of other potential mechanisms of social cognitive response to interventions remain.

Digital literacy as a new determinant of health: A scoping review.

INTRODUCTION: Harnessing new digital technologies can improve access to health care but can also widen the health divide for those with poor digital literacy. This scoping review aims to assess the current situation of low digital health literacy in terms of its definition, reach, impact on health and interventions for its mitigation. METHODS: A comprehensive literature search strategy was composed by a qualified medical librarian. Literature databases [Medline (Ovid), Embase (Ovid), Scopus, and Google Scholar] were queried using appropriate natural language and controlled vocabulary terms along with hand-searching and citation chaining. We focused on recent and highly cited references published in English. Reviews were excluded. This scoping review was conducted following the methodological framework of Arksey and O'Malley. RESULTS: A total of 268 articles were identified (263 from the initial search and 5 more added from the references of the original papers), 53 of which were finally selected for full text analysis. Digital health literacy is the most frequently used descriptor to refer to the ability to find and use health information with the goal of addressing or solving a health problem using technology. The most utilized tool to assess digital health literacy is the eHealth literacy scale (eHEALS), a self-reported measurement tool that evaluates six core dimensions and is available in various languages. Individuals with higher digital health literacy scores have better self-management and participation in their own medical decisions, mental and psychological state and quality of life. Effective interventions addressing poor digital health literacy included education/training and social support. CONCLUSIONS: Although there is interest in the study and impact of poor digital health literacy, there is still a long way to go to improve measurement tools and find effective interventions to reduce the digital health divide.

Biased brain and behavioral responses towards kin in males of a communally breeding species.

In complex social environments, individuals may interact with not only novel and familiar conspecifics but also kin and non-kin. The ability to distinguish between conspecific identities is crucial for most animals, yet how the brain processes conspecific type and how animals may alter behavior accordingly is not well known. We examined whether the communally breeding spiny mouse (Acomys cahirinus) responds differently to conspecifics that vary in novelty and kinship. In a group interaction test, we found that males can distinguish novel kin from novel non-kin, and preferentially spend time with novel kin over familiar kin and novel non-kin. To determine whether kinship and novelty status are differentially represented in the brain, we conducted immediate early gene tests, which revealed the dorsal, but not ventral, lateral septum differentially processes kinship. Neither region differentially processes social novelty. Further, males did not exhibit differences in prosocial behavior toward novel and familiar conspecifics but exhibited more prosocial behavior with novel kin than novel non-kin. These results suggest that communally breeding species may have evolved specialized neural circuitry to facilitate a bias to be more affiliative with kin, regardless of whether they are novel or familiar, potentially to promote prosocial behaviors, thereby facilitating group cohesion.

Prevalence of pre-diabetes in adults aged 25 - 45 years in a Durban-based clinical setting, South Africa: A retrospective study.

AIM: Due to pre-diabetes being underexplored, its prevalence was investigated in study participants aged 25-45 years in a Durban-based tertiary-level clinical setting in South Africa. METHODS: The study was done using a retrospective study design. Fasting blood samples from consented patients with no previous diagnosis of diabetes and within the specified age range were collected from King Edward Hospital in Durban. The pre-diabetes diagnosis was confirmed in participants with fasting glucose concentrations between 5.6 and 6.9 mmol/L and glycated haemoglobin (HbA1c) levels between 5.7 % and 6.4 % using the American Diabetes Association (ADA) and World Health Organisation (WHO) diagnosis criteria. The study participants' characterisation was stratified according to the diagnosis criterion, age, gender and ethnicity. RESULTS: An alarming 68 % average pre-diabetes prevalence across ADA and WHO criteria in the Durban, eThekwini district sample population. The highest prevalence was recorded using the IFG criterion (83%) and the lowest when using the HbA1c criterion (54 %). Between the White, Black and Indian ethnic groups, the Indian group were more predisposed to pre-diabetes onset, with a prevalence of 62.7 %. CONCLUSION: If pre-diabetes management is unattended, an unprecedented increase in metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and all-cause mortality incidence can be expected. Therefore, the study reveals a window of opportunity to intensify preventative measures and mitigate the incidence of T2DM.

Within-Person Relationship between Attenuated Positive Symptoms and Suicidal Ideation among Individuals at Clinical High Risk for Psychosis.

Individuals at clinical high-risk for psychosis (CHR-P) are at increased risk for suicide. However, the relationship between attenuated positive symptoms and suicidal ideation are not well understood, particularly as they interact over time. The current study addressed this gap in the literature. We hypothesized that greater attenuated symptoms would be concurrently and prospectively associated with suicidal ideation. Further, we hypothesized that suspiciousness and perceptual abnormalities would have the strongest relationship with suicidal ideation. Within-person variation in symptoms and suicidal ideation were examined across 24 treatment sessions for individuals at CHR-P. Attenuated positive symptoms (unusual thought content, suspiciousness, grandiose ideas, perceptual abnormalities, and disorganized communication) and suicidal ideation were assessed at each session. Logistic mixed effect models examined concurrent and time-lagged relationships between symptoms and suicidal ideation among 36 individuals at CHR-P. Results indicated that suicidal ideation was more likely during weeks when participants reported more severe total attenuated positive symptoms. Further, suspiciousness was uniquely associated with suicidal ideation, both concurrently and at the following session. Post hoc models examined the reverse direction of this relationship, demonstrating that suicidal ideation also prospectively predicted suspiciousness at the following session. These results suggest that within-person attenuated symptoms, particularly suspiciousness, are associated with suicidal ideation among individuals at CHR-P. However, the bidirectional relationship between suspiciousness and suicidal ideation raises questions about causal nature of this relationship. Further research is needed to examine the dynamic interplay of suspiciousness and suicidal ideation.

Testosterone facilitates nonreproductive, context-appropriate pro- and anti-social behavior in female and male Mongolian gerbils.

A growing body of literature suggests that testosterone (T) rapidly modulates behavior in a context-specific manner. However, the timescales in which T can rapidly mediate distinct types of behavior, such as pro- vs. anti- social responses, has not been studied. Thus, here we examined acute T influences on social behavior in male and female Mongolian gerbils in nonreproductive contexts. Females and males received an injection of either saline or T and were first tested in a social interaction test with a same-sex, familiar peer. 5 min after the peer interaction, subjects then underwent a resident-intruder test with a novel, same-sex conspecific. After another 5 min, gerbils were tested in a novel object task to test context-specificity (i.e., social vs. nonsocial) of T effects on behavior. Within 1 h, males and females injected with T exhibited more huddling with a peer but more active avoidance of and less time spent in proximity of an intruder than did animals injected with saline. T effects on behavior were specific to social contexts, such that T did not influence investigation of the novel object. Together these findings show that T rapidly promotes pro-social responses to a familiar peer and anti-social responses to an intruder in the same individuals within 5 min of experiencing these disparate social contexts. This demonstrates that T rapidly facilitates behavior in a context-appropriate manner outside the context of reproduction and reveals that rapid effects of T on behavior are not restricted to males.

Executively-mediated language skills are related to performance-based social functioning in the early psychosis spectrum.

Social impairment is a core deficit in psychotic spectrum disorders (PSDs). Prior work shows that language abnormalities can predict psychosis onset and are related to social outcomes in PSDs. Few studies have investigated nuanced relationships between language/verbal abilities and social functioning in the early psychosis spectrum, including at-risk (schizotypy) and first episode of psychosis (FEP) individuals. This study aimed to examine the relationship to between language/verbal performance and performance-based and examiner-rated social functioning. We also aimed to replicate prior models that demonstrate neurocognition is related to social functioning through negative symptoms and social cognition. Low schizotypy (n = 42), high schizotypy (n = 44), and FEP (n = 15) participants completed a battery of language/verbal, social cognition, and social functioning measures. Regression analyses revealed that Proverb Test performance was uniquely and significantly associated with performance-based but not examiner-rated social functioning. Other language/verbal measures were not significantly related to social functioning. In mediational analyses, language/verbal performance was indirectly related to social functioning through negative traits, and also through social cognition. Findings extend support for negative symptom and social cognitive intervention in the early psychosis spectrum, and uniquely suggest that executively-mediated language skills may be an additional target to improve social functioning.

Lower cohesion and altered first-person pronoun usage in the spoken life narratives of individuals with schizophrenia.

Usage of computational tools to quantify language disturbances among individuals with psychosis is increasing, improving measurement efficiency and access to fine-grained constructs. However, few studies apply automated linguistic analysis to life narratives in this population. Such research could facilitate the measurement of psychosis-relevant constructs such as sense of agency, capacity to organize one's personal history, narrative richness, and perceptions of the roles that others play in one's life. Furthermore, research is needed to understand how narrative linguistic features relate to cognitive and social functioning. In the present study, individuals with schizophrenia (n = 32) and individuals without a psychotic disorder (n = 15) produced personal life narratives within the Indiana Psychiatric Illness Interview. Narratives were analyzed using the Coh-Metrix computational tool. Linguistic variables analyzed were indices of connections within causal and goal-driven speech (deep cohesion), unique word usage (lexical diversity), and pronoun usage. Individuals with schizophrenia compared to control participants produced narratives that were lower in deep cohesion, contained more first-person singular pronouns, and contained fewer first-person plural pronouns. Narratives did not significantly differ between groups in lexical diversity, third-person pronoun usage, or total word count. Cognitive-linguistic relationships emerged in the full sample, including significant correlations between greater working memory capacity and greater deep cohesion and lexical diversity. In the schizophrenia group, social problem-solving abilities did not correlate with linguistic variables but were associated with cognition. Findings highlight the relevance of psychotherapies which aim to promote recovery among individuals with psychosis through the construction of coherent life narratives and increasing agency and social connectedness.

Distribution of Vasopressin 1a and Oxytocin Receptor Binding in the Basal Forebrain and Midbrain of Male and Female Mongolian Gerbils.

The nonapeptide system modulates a diversity of social behaviors, including aggression, parental care, affiliation, sexual behavior, and pair bonding. Such social behaviors are regulated through oxytocin and vasopressin activation of the oxytocin receptor (OXTR) and vasopressin V1a receptor (AVPR1A) in the brain. Nonapeptide receptor distributions have been mapped for several species, however, studies have demonstrated that there is substantial variation across species. Mongolian gerbils (Meriones unguiculatus) are an excellent organism for studying family dynamics, social development, pair bonding, and territorial aggression. Although an increasing number of studies are examining the neural mechanisms of social behavior in Mongolian gerbils, nonapeptide receptor distributions have yet to be characterized for this species. Here we conducted receptor autoradiography to map distributions of OXTR and AVPR1A binding throughout the basal forebrain and midbrain of female and male Mongolian gerbils. Further, we assessed whether gonadal sex influenced binding densities in brain regions important for social behavior and reward, however, we observed no effects of sex on OXTR or AVPR1A binding densities. These findings provide mapping distributions of nonapeptide receptors in male and female Mongolian gerbils, laying a foundation for future studies that seek to manipulate the nonapeptide system to examine nonapeptide-mediated social behavior.

Discrepancies between self and caregiver perceptions of agency in first-episode psychosis.

Personal agency-a key element of recovery from psychotic disorders-is formed and maintained in large part through interactions with others. Interactions with caregivers are particularly important in first-episode psychosis (FEP), as these interactions form the foundations for lifelong caregiving relationships. The present study examined shared understandings of agency (operationalized as efficacy to manage symptoms and social behaviors) within families affected by FEP. Individuals with FEP (n = 46) completed the Self-Efficacy Scale for Schizophrenia (SESS) and measures of symptom severity, social functioning, social quality of life, stigma, and discrimination. Caregivers (n = 42) completed a caregiver version of the SESS assessing perceptions of their affected relative's self-efficacy. Self-rated efficacy was higher than caregiver-rated efficacy in all domains (positive symptoms, negative symptoms, and social behavior). Self- and caregiver-rated efficacy correlated only in the social behavior domain. Self-rated efficacy was most associated with lower depression and stigmatization, whereas caregiver-rated efficacy was most associated with better social functioning. Psychotic symptoms did not relate to self- or caregiver-rated efficacy. Individuals with FEP and caregivers have discrepant perceptions of personal agency, perhaps because they base perceptions of agency on different sources of information. These findings highlight specific targets for psychoeducation, social skills training, and assertiveness training to develop shared understandings of agency and facilitate functional recovery.

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor (Oxtr) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species (n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.