Childhood trauma and amygdala nuclei volumes in youth at risk for mental illness.

BACKGROUND: Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth. METHODS: Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure. RESULTS: Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment. CONCLUSION: The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.

Trauma in Youth At-Risk for Serious Mental Illness.

Childhood trauma has been shown to have detrimental consequences on mental health. It is unknown what impact childhood trauma may have on the early trajectory of serious mental illness (SMI). The purpose of this article is to estimate the baseline prevalence, perceived impact, and duration of trauma that occurred before the age of 18 years in youth at risk for SMI using a transdiagnostic approach. This study included 243 youths, ages 12 to 25 years (42 healthy controls, 43 non-help-seeking individuals [stage 0], 52 help-seeking youth experiencing distress and possibly mild symptoms of anxiety or depression [stage1a], and 108 youth demonstrating attenuated symptoms of an SMI such as bipolar disorder or psychosis [stage 1b]). Participants completed an adapted version of the Childhood Trauma and Abuse scale. There were high frequencies of reported trauma across all stages. Symptomatic individuals experienced more trauma and bullying. Stage 1b individuals reported more physical abuse. Stage 1b also indicated psychological bullying to have a longer duration and impact on their lives. Future work should aim to clarify the complex interrelations between trauma and risk of SMI.

Sleep disturbances in youth at-risk for serious mental illness.

AIM: To investigate sleep behaviours of youth at-risk for serious mental illness (SMI). METHODS: This study included 243 youth, ages 12 to 25:42 healthy controls, 41 asymptomatic youth at-risk for mental illness (stage 0); 53 help-seeking youth experiencing distress (stage 1a) and 107 youth with attenuated syndromes (stage 1b). The Pittsburgh Sleep Quality Index was used to assess sleep dysfunction. RESULTS: Stage 1b individuals indicated the greatest deficit in global sleep dysfunction (F = 26.18, P < .0001). Stages 1a and 1b reported significantly worse subjective sleep quality, a longer sleep latency, increased use of sleep medications as well as greater daytime dysfunction compared to the asymptomatic groups. CONCLUSION: Research investigating sleep behaviours of youth considered to be at-risk for SMI is limited. This study provides early evidence that sleep disturbances are worse for individuals considered to be at higher risk of illness development.

Predictors of Transition to Psychosis in Individuals at Clinical High Risk.

PURPOSE OF REVIEW: Current research is examining predictors of the transition to psychosis in youth who are at clinical high risk based on attenuated psychotic symptoms (APS). Determining predictors of the development of psychosis is important for an improved understanding of mechanisms as well as the development of preventative strategies. The purpose is to review the most recent literature identifying predictors of the transition to psychosis in those who are already assessed as being at risk. RECENT FINDINGS: Multidomain models, in particular, integrated models of symptoms, social functioning, and cognition variables, achieve better predictive performance than individual factors. There are many methodological issues; however, several solutions have now been described in the literature. For youth who already have APS, predicting who may go on to later develop psychosis is possible. Several studies are underway in large consortiums that may overcome some of the methodological concerns and develop improved means of prediction.

Clinical staging for youth at-risk for serious mental illness.

AIM: The first aim of this project was to identify a sample of youth who met different stages of risk for the development of a serious mental illness (SMI) based on a published clinical staging model. The second aim was to determine whether participants allocated to the different stages were a good fit to the model by comparing these groups on a range of clinical measures. METHODS: This two-site longitudinal study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 43 non-help seeking individuals with no mental illness but with some risk of SMI, such as having a first-degree relative with a SMI (stage 0), (c) 52 help-seeking youth experiencing distress and possibly mild symptoms of anxiety or depression (stage 1a) and (d) 108 youth with attenuated symptoms of SMI, such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself. RESULTS: There were no clinical differences between HCs and participants in stage 0. For most of the clinical measures, participants in stage 1b had more severe ratings than participants in stages 1a and 0 and HCs; those in stage 1a had more severe ratings than HCs and stage 0 participants. CONCLUSIONS: These results suggest that the staging process used to allocate participants to various stages is a good fit. That is, the clinical ratings followed an ordering effect consistent with that hypothesized in the staging model.

The role of a family history of psychosis for youth at clinical high risk of psychosis.

AIM: On average, there is a 10% to 12% likelihood of developing a psychotic disorder solely based on being at familial high risk. However, the introduction of the criteria for clinical high risk (CHR) of psychosis suggested for CHR individuals, 20% to 30% will go on to develop a full-blown psychotic illness within 3 years. Several studies suggest a role for family history in conversion to psychosis among those at CHR. However, we know very little about those who meet the CHR criteria and have a positive family history for psychosis compared to those at CHR with no known family history. The aim of this study was to compare these 2 groups on demographics, clinical symptoms, social and role functioning, IQ, environmental factors and conversion to psychosis. METHOD: A total of 762 participants met criteria for being at CHR, 119 of whom had a family history (CHR + FH) and 643 without (CHR-FH). Groups were compared on attenuated symptoms, role and social functioning, IQ, past trauma, perceived discrimination and cannabis use. Survival analysis was used to compare groups on conversion rates. RESULTS: There were no major differences between the groups in symptoms, functioning, IQ, cannabis use or in the rate of conversion between the groups. The CHR + FH group reported increased amounts of early trauma. CONCLUSION: There is a possibility that CHR + FH individuals believe that it is more difficult for them to cope with circumstances such as abuse or potential abuse. Future research on this subject should investigate family environment and its role in conversion to psychosis among CHR + FH individuals.

Clinical and functional characteristics of youth at clinical high-risk for psychosis who do not transition to psychosis.

BACKGROUND: Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis. METHODS: In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups - those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe. RESULTS: There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls. CONCLUSIONS: A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.

Early traumatic experiences, perceived discrimination and conversion to psychosis in those at clinical high risk for psychosis.

PURPOSE: There is evidence to suggest that both early traumatic experiences and perceived discrimination are associated with later onset of psychosis. Less is known about the impact these two factors may have on conversion to psychosis in those who are at clinical high risk (CHR) of developing psychosis. The purpose of this study was to determine if trauma and perceived discrimination were predictors of conversion to psychosis. METHODS: The sample consisted of 764 individuals who were at CHR of developing psychosis and 280 healthy controls. All participants were assessed on past trauma, bullying and perceived discrimination. RESULTS: Individuals at CHR reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis. CONCLUSIONS: Given that CHR individuals are reporting increased rates of trauma and perceived discrimination, these should be routinely assessed, with the possibility of offering interventions aimed at ameliorating the impact of past traumas as well as improving self-esteem and coping strategies in an attempt to reduce perceived discrimination.

Core Schemas in Youth at Clinical High Risk for Psychosis.

BACKGROUND: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. AIMS: To investigate schemas over time in a large sample of CHR individuals and healthy controls. METHOD: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. RESULTS: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. CONCLUSIONS: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.

Screening tools for clinical high risk for psychosis.

AIM: The purpose of this article was to review existing screening instruments that could be used to identify individuals who may be at increased risk for psychosis and to determine the suitability of these instruments. METHODS: Medline (Ovid) and PubMed were searched for peer-reviewed articles published in English, which reported performance evaluation of screening instruments for symptoms of high risk for psychosis. The articles' titles, abstracts and, when necessary, full texts were read to filter them against the selection criteria. Citations within relevant articles were hand searched for other potentially eligible studies. RESULTS: This selection strategy resulted in identifying 56 articles (including three articles available only in an abstract format) that reported performance evaluation of 17 screening instruments. CONCLUSIONS: The sensitivity of these scales ranged from 67% to 100% and the specificity ranged from 39% to 100%. The positive predictive value was less precise with scores ranging from 24% to 100%, and the negative predictive value ranging from 58% to 100%. There were several scales that might be useful for screening for individuals who are at increased risk for developing psychosis; however, the majority of measures are underexplored with poor validation.

Personal Beliefs about Experiences in those at Clinical High Risk for Psychosis.

BACKGROUND: Negative beliefs about illness in early psychosis have been shown to have an unfavourable impact on one's quality of life. A shift of focus in psychosis research has been on the detection of individuals considered to be at clinical high risk (CHR) of developing psychosis. Little is known about the impact that beliefs about psychotic like experiences or attenuated psychotic symptoms may have on CHR individuals. AIM: To explore these beliefs in a large sample of young people at CHR of developing psychosis using the Personal Beliefs about Experiences Questionnaire (PBEQ). METHOD: Beliefs about unusual experiences were assessed in 153 CHR individuals with the PBEQ. Prodromal symptoms (measured by the SIPS) and depression (measured by the CDSS) were also assessed. RESULTS: In CHR individuals, holding more negative beliefs was associated with increased severity in depression and negative symptoms. Higher scores on suspiciousness were associated with increased negative beliefs, and higher levels of grandiosity were associated with decreased negative beliefs. Those who later transitioned to psychosis agreed significantly more with statements concerning control over experiences (i.e. "my experiences frighten me", "I find it difficult to cope). CONCLUSIONS: The results suggest that targeting negative beliefs and other illness related appraisals is an important objective for intervention strategies.

Perceived discrimination in those at clinical high risk for psychosis.

AIM: There is evidence to suggest that perceived discrimination may be associated with psychosis. Less is known about its potential impact on those at clinical high risk (CHR) for psychosis. The aim of this study was to determine the prevalence of perceived discrimination in a CHR sample and its possible relationship to attenuated positive symptoms and negative self-beliefs. METHODS: Participants were 360 CHR individuals and 180 healthy controls. Assessments included a self-report measure of perceived discrimination, the Scale of Prodromal Symptoms and the Brief Core Schema Scale. RESULTS: CHR participants reported significantly more perceived discrimination. Perceived discrimination was significantly associated with negative schemas, but not with attenuated positive symptoms. CONCLUSIONS: These results suggest that individuals at CHR for psychosis endorse a higher level of perceived discrimination, which is associated with increased negative schemas, but not attenuated positive symptoms.

Predictors of a clinical high risk status among individuals with a family history of psychosis.

BACKGROUND: Risk for psychosis can be assessed on the basis of genetic risk, referred to in the literature as family high risk (FHR) or through the presence of clinical high risk symptoms (CHR). Recent studies have also shown that certain risk factors (i.e. trauma, cannabis, migration) may play a role in the development of psychosis, possibly in combination with one another and in particular in combination with a family history of psychosis. It is unknown which risk factors may play a role in the prediction of CHR status among individuals whom are already genetically vulnerable. This study compared FHR individuals who also met CHR criteria to FHR individuals who did not on various risk factors, psychopathology and functioning. METHOD: Participants were 25 who met FHR and CHR criteria (FHR + CHR) as determined by Structured Interview for Prodromal Syndromes, 25 who met only FHR criteria (FHR-non-CHR), and 25 healthy controls. A binary logistic regression was performed to determine the best predictors of belonging to the FHR + CHR group. RESULTS: FHR + CHR and FHR-non CHR were significantly different on measures of age first tried cannabis (F = 3.65, p < 0.05) and IQ (F = 3.32, p < 0.05). FHR groups also differed on self-reported anxiety (F=11.79, p < 0.001) and current scores of social (F = 19.74, p < 0.0001) and role (F = 17.71, p < 0.0001) functioning. The most significant predictor of belonging to the FHR + CHR group was an earlier age of cannabis use (OR = 0.44, p = 0.05). CONCLUSION: These preliminary results are promising in determining potential risk factors for the development of psychosis in those who are at risk for psychosis on the basis of a family history.

Early traumatic experiences in those at clinical high risk for psychosis.

AIM: Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic-like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis. METHODS: The sample consisted of 360 individuals who were at CHR of developing psychosis and 180 age- and gender-matched healthy controls. All participants were assessed on past trauma and bullying. The CHR participants were also assessed on a range of psychopathology and functioning. RESULTS: Individuals at CHR reported significantly more trauma and bullying than healthy controls. Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self. CONCLUSIONS: These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms.

Pathways to care for those at clinical high risk of developing psychosis.

AIM: Understanding the pathways to care is a prerequisite for early detection in first-episode patients with psychosis. Less in known about the pathways to care for individuals at clinical high risk for psychosis. METHODS: A sample of 35 clinical high risks for psychosis individuals were administered a semistructured questionnaire inquiring about pathways to care. RESULTS: The majority of contacts were made to general practitioners (32.8%). Various symptoms of concern were reported among the sample, the most common being depression (15.9%) followed by anxiety (11.0%). Delusions/paranoia were the most frequent symptoms associated with successful referral to contacts (14.3%). CONCLUSION: Education on the pathway to successful access to care and treatment in a putatively prodromal for psychosis group of individuals is valuable information that can potentially aid in a faster discovery of these individuals and their access to treatment and care.

Predictors of disengagement from treatment in an early psychosis program.

BACKGROUND: Disengagement from treatment is a major concern in psychiatry. This is of particular concern for those presenting for care at their first episode of psychosis (FEP). The purpose of this study is to determine the rate of disengagement from a three year FE treatment program and the predictors of disengagement. METHOD: We used a longitudinal cohort design. The cohort consisted of 286 FEP individuals. Measures included assessments of positive and negative symptoms, depression, substance use, premorbid and current functioning, cognition and duration of untreated psychosis. Disengagement from treatment was defined as leaving the program before the 30 months. RESULTS: At 30 months after treatment, the estimated rate of disengagement from treatment was 31%. Predictors of disengagement were examined via Cox proportional hazards models which revealed that lower ratings on negative symptom scores at baseline (HR=0.946; CI=0.909-0.985), a shorter duration of untreated psychosis (HR=0.997; CI=0.994-0.999), and not having a family member involved in the program (HR=0.310; CI=0.196-0.490) contributed significantly to predicting disengagement from treatment. An examination of those who dropped out at different times revealed that those who dropped out prior to 6 months had significantly greater cannabis (p<0.05) and other drug use (p<0.01). CONCLUSIONS: Engagement in early services may be helped by attending carefully to substance use to prevent early dropout, to those who may have had a short duration of untreated psychosis and to working with families to engage families in the program.

Maladaptive schemas as a mediator between social defeat and positive symptoms in young people at clinical high risk for psychosis.

AIM: Social defeat may be the mechanism that links past social adversities with the development of psychosis. In depression research, it is accepted that adverse early social experiences can lead to enduring cognitive vulnerabilities, characterized by negative schemas about the self and others. The aim of this study was to examine whether negative beliefs about the self and others link social defeat to early signs of psychosis. METHODS: Data from a sample of individuals at high risk for developing psychosis (n = 38) were assessed using measures of social defeat and schemas. RESULTS: High levels of social defeat and negative evaluations of the self and others were displayed. Negative beliefs mediated the relationship between social defeat and early symptoms, offering some support for the notion that maladaptive self-beliefs play a role in the onset of psychosis. CONCLUSIONS: These results have implications for prevention because these maladaptive schemas are malleable factors for which we have effective psychological interventions.

Processing of ironic language in children with high-functioning autism spectrum disorder.

We examined processing of verbal irony in three groups of children: (1) 18 children with high-functioning Autism Spectrum Disorder (HFASD), (2) 18 typically- developing children, matched to the first group for verbal ability, and (3) 18 typically-developing children matched to the first group for chronological age. We utilized an irony comprehension task that minimized verbal and pragmatic demands for participants. Results showed that children with HFASD were as accurate as typicallydeveloping children in judging speaker intent for ironic criticisms, but group differences in judgment latencies, eye gaze, and humor evaluations suggested that children with HFASD applied a different processing strategy for irony comprehension; one that resulted in less accurate appreciation of the social functions of irony.