High Risk For Psychotic Disorders Research Articles

Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders

IntroductionClinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a ‘gatekeeper’ for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population. MethodThe sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis. ResultsReplication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c=0.51). Retraining resulted in moderate discrimination (Harrel's c=0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0–23.1%) over two years. ConclusionFailure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention.

Developmental profiles of schizotypy in the general population: A record linkage study of Australian children aged 11-12 years.

ObjectivesThe detection of young people at high risk for psychotic disorders has been somewhat narrowly focused on overt symptom‐based markers that reflect mild reality distortion (e.g., psychotic‐like experiences), or prodromal syndromes that are proximal to psychosis onset. The concept of schizotypy represents a broader framework for investigating risk for schizophrenia (and other disorders) in childhood, before the onset of prodromal or overt symptoms. We sought to detect profiles of risk for psychosis (schizotypy) in a general population sample of 22,137 Australian children aged 11–12 years, and to determine early life risk factors associated with these profiles from data available in linked records (registers).MethodsFifty‐nine self‐reported items were used as indicators of schizotypy across six broad domains; z‐scores for each domain were subjected to latent profile analyses (LPA). A series of multinomial logistic regressions was used to examine the association between resulting profile (class) membership and several childhood and parental risk factors, and the proportion of children with mental disorders among each schizotypy profile was examined.ResultsThe LPA revealed three person‐centred profiles referred to as True Schizotypy (n = 1,323; 6.0%), Introverted Schizotypy (n = 4,473; 20.2%), and Affective Schizotypy (n = 4,261; 19.2%), as well as a group of children showing no risk (n = 12,080; 54.6%). Prior exposure to perinatal and familial adversities including childhood maltreatment, as well as poor early childhood development and academic functioning, was variously associated with all risk groups. There was a higher proportion of childhood mental disorder diagnoses among children in the True Schizotypy group, relative to other profiles.ConclusionSubtle differences in the pattern of exposures and antecedents among schizophrenia liability profiles in childhood may reflect distinct pathogenic pathways to psychotic or other mental illness.Practitioner points Children aged 11–12 years report characteristics of schizotypy which can be classified into three distinct profiles that may represent different pathological processes towards later mental ill‐health.Early life exposure to perinatal and familial adversities including childhood maltreatment, early childhood developmental vulnerability, and poor academic functioning predict membership in all three childhood schizotypy profiles.Latent liability for schizophrenia (and potentially other mental disorders) may be represented by different profiles of functioning observable in childhood.

Transdiagnostic Dimensions of Psychiatric Comorbidity in Individuals at Clinical High Risk for Psychosis: A Preliminary Study Informed by HiTOP.

Background: Although psychiatric comorbidity is the norm among individuals at clinical high risk for psychotic disorders (CHR), research has yet to examine transdiagnostic dimensional models of comorbidity in this critical population.Methods: This study analyzed quantitative measures of eleven psychiatric syndromes in a group at CHR (n = 71) and a matched healthy comparison group (n = 73) to determine these syndromes' dimensional structure and relationships to cognition, functioning, and risk of conversion to psychotic disorders.Results: Relative to the comparison group, the CHR group was elevated on all eleven psychiatric syndromes. Exploratory factor analysis found three psychopathology dimensions: internalizing, negative symptoms, and positive symptoms. Depression cross-loaded onto the internalizing and negative symptom dimensions. Hypomania loaded positively on positive symptoms but negatively on negative symptoms. The negative symptom factor was associated with poorer cognition and functioning and a higher risk of conversion to psychosis.Conclusions: These dimensions align with internalizing, detachment, and thought disorder, three of the five spectra in higher-order models such as the Hierarchical Taxonomy of Psychopathology (HiTOP). In the CHR state, detachment appears to be particularly insidious and predictive of psychosis. Further research is required to distinguish depression and hypomania from attenuated psychotic symptoms in this population.

Three types of psychotic-like experiences in youth at clinical high risk for psychosis.

A fully dimensional model of psychosis implies that psychotic-like experiences (PLEs) connect the entire psychosis spectrum. Three types of self-reported PLEs-persecutory ideation, bizarre experiences, and perceptual abnormalities-are commonly found in the general population. This study assessed the construct, predictive, and incremental validity of self-reported PLEs in youth at clinical high risk for psychotic disorders (CHR). Self-report data on PLEs (community assessment of psychic experiences; CAPE) were collected from 105 CHR youth (mage = 19.3). Interview measures of attenuated psychotic symptoms and self-report measures of psychosis proneness, depression, and anxiety were collected at baseline and 12-month follow-up (n = 70 at follow-up). Factor, cross-sectional, and longitudinal analyses examined relationships between study variables. Self-reported PLEs were best represented by the same three factors found in the general population: persecutory ideation, bizarre experiences, and perceptual abnormalities. Cross-sectionally, PLEs-particularly persecutory ideation-correlated with interview-rated attenuated psychotic symptoms and self-reported psychosis proneness, depression, and anxiety. Longitudinally, baseline PLEs trended toward predicting 12-month change in positiveattenuated psychotic symptoms (r = .29, pFDR = .058). Incrementally, baseline PLEs predicted 12-month change in positive and disorganized symptoms, when accounting for the effect of baseline positive symptoms and demographics. Three types of PLEs were valid in this CHR sample. Self-reported PLEs may be used not only to screen individuals for inclusion in the CHR classification, but also to characterize individuals within this population. Self-reported PLEs may help to forecast which CHR individuals will progress toward psychotic illness.

Subcortical Brain Volume Abnormalities in Individuals With an At-risk Mental State.

Previous structural magnetic resonance imaging studies of psychotic disorders have demonstrated volumetric alterations in subcortical (ie, the basal ganglia, thalamus) and temporolimbic structures, which are involved in high-order cognition and emotional regulation. However, it remains unclear whether individuals at high risk for psychotic disorders with minimal confounding effects of medication exhibit volumetric changes in these regions. This multicenter magnetic resonance imaging study assessed regional volumes of the thalamus, caudate, putamen, nucleus accumbens, globus pallidus, hippocampus, and amygdala, as well as lateral ventricular volume using FreeSurfer software in 107 individuals with an at-risk mental state (ARMS) (of whom 21 [19.6%] later developed psychosis during clinical follow-up [mean = 4.9 years, SD = 2.6 years]) and 104 age- and gender-matched healthy controls recruited at 4 different sites. ARMS individuals as a whole demonstrated significantly larger volumes for the left caudate and bilateral lateral ventricles as well as a smaller volume for the right accumbens compared with controls. In male subjects only, the left globus pallidus was significantly larger in ARMS individuals. The ARMS group was also characterized by left-greater-than-right asymmetries of the lateral ventricle and caudate nucleus. There was no significant difference in the regional volumes between ARMS groups with and without later psychosis onset. The present study suggested that significant volume expansion of the lateral ventricle, caudate, and globus pallidus, as well as volume reduction of the accumbens, in ARMS subjects, which could not be explained only by medication effects, might be related to general vulnerability to psychopathology.

Violence and Suicide Risk Assessment in Youth with Psychotic Disorders: Practical Considerations for Community Clinicians.

Psychosis is a unique and significant risk factor associated with violent and suicidal behavior and warrants special consideration. This article presents a careful review of the literature on violence risk and psychosis and suicide risk and psychosis as it pertains to youth or those who have been newly diagnosed with or are at high risk for psychotic disorders. Each topic is covered in reference to general considerations and specific psychotic symptoms (eg, hallucinations, delusions, paranoia). The reader can refer to practical boxes to assist in identifying relevant risk factors and examples of questions to ask the patient and family.

61.3 NEUROBIOLOGICAL TRAJECTORIES IN EARLY PSYCHOSIS: FINDINGS FROM NEUROIMAGING STUDIES

Our understanding of the neurobiology underlying illness trajectories in early psychosis remains largely unknown. Recent efforts via neuroimaging measures have shed light on neural systems that play roles in illness phases ranging from patients at clinical high risk for psychotic disorders to patients beyond their first episode of a schizophrenia spectrum disorder.

Assessment and treatment of individuals at high risk for psychosis

SUMMARYEarly detection and specialised early intervention for people at high risk for psychotic disorders have received growing attention in the past few decades, with the aim of delaying or preventing the outbreak of explicit psychotic symptoms and improving functional outcomes. This article summarises criteria for a diagnosis of high psychosis risk, the implications for such a diagnosis and recommendations for treatment.LEARNING OBJECTIVESAfter reading this article you will be able to: •recognise signs and symptoms indicating increased psychosis risk•understand uses and limitations of screening for high psychosis risk, and interpretation of results•recognise evidence-based treatment options for patients at clinical high risk for psychosis.DECLARATION OF INTERESTC.A. has received non-financial support from Sunovion and Lundbeck in the past 36 months.

Dissociable Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions.

The 22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional connectivity MRI studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of human youth with 22q11DS (n = 42; 59.5% female) and demographically matched healthy controls (n = 39; 53.8% female). Neuroimaging data were acquired via single-band protocols and analyzed in line with methods provided by the Human Connectome Project. We computed functional relationships between individual-specific anatomically defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain Type I error protection was achieved through nonparametric permutation-based methods. The 22q11DS patients displayed dissociable disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamocortical coupling was increased in somatomotor regions and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to somatomotor and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggests that high genetic risk for psychiatric illness is linked with disruptions in large-scale corticosubcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect copy number variants for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENT Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. The 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a dissociable fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.

Poster #M155 MEDIATION MODELS OF THE RELATIONSHIP BETWEEN CHILDHOOD TRAUMA AND DEPRESSIVENESS IN PATIENTS AT-RISK FOR PSYCHOSIS AND IN HELP-SEEKING CONTROLS

Cognitive deficits have been well documented in individuals with bipolar disorder (BD) after the first episode of mania. However, little is known about the presence of such deficits prior to the initial manic episode.Participants were recruited from a cohort of 416 young people who were at ultra-high risk (UHR) for psychosis and were followed up between 4 and 13 years later. The current report is of 16 participants who developed BD over a mean follow-up period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive assessment scores were compared with those of 46 age and gender matched UHR subjects who did not transition to psychosis or BD over the follow-up period (UHR-NT) and 66 healthy comparison subjects.UHR-BD subjects had lower global functioning at baseline compared with UHR-NT subjects. There were no significant differences between UHR-BD and UHR-NT subjects on baseline demographic and neurocognitive characteristics. UHR-BD subjects had lower test performance than HC on picture completion, Trail-Making Tests and measures of global intelligence.Small sample size, limited and variable neurocognitive tests utilised and the confounding effects of psychotic symptoms might have impacted on the ability to detect meaningful clinical and neurocognitive differences.In this exploratory study, neurocognition in young people who later develop BD is similar to those of subjects who are at a high risk for psychotic disorders, but there may be certain neurocognitive markers that distinguish this group from unaffected and healthy young people.

Pathways to care in subjects at high risk for psychotic disorders — A European perspective

Evidence-based decisions on indicated prevention in early psychosis require large-scale studies on the pathways to care in high-risk subjects. EPOS (The European Prediction of Psychosis Study), a prospective multi-center, naturalistic field study in four European countries (Finland, Germany, The Netherlands and England), was designed to acquire accurate knowledge about pathways to care and delay in obtaining specialized high risk care. Our high risk sample (n=233) reported on average 2.9 help-seeking contacts, with an average delay between onset of relevant problems to initial help-seeking contact of 72.6weeks, and between initial help-seeking contact and reaching specialized high risk care of 110.9weeks. This resulted in a total estimated duration of an unrecognized risk for psychosis of 3 ½years. Across EPOS EU regions, about 90% of care pathway contacts were within professional health care sectors. Between EPOS regions, differences in the pathways parameters including early detection and health-care systems were often very pronounced. High-risk participants who later made transition to a full psychotic disorder had significantly longer delays between initial help-seeking and receiving appropriate interventions. Our study underlines the need for regionally adapted implementation of early detection and intervention programs within respective mental health and health care networks, including enhancing public awareness of early psychosis.

Neurocognitive functioning in the prodrome of mania—an exploratory study

BackgroundCognitive deficits have been well documented in individuals with bipolar disorder (BD) after the first episode of mania. However, little is known about the presence of such deficits prior to the initial manic episode. MethodsParticipants were recruited from a cohort of 416 young people who were at ultra-high risk (UHR) for psychosis and were followed up between 4 and 13 years later. The current report is of 16 participants who developed BD over a mean follow-up period of 8.2 years (UHR-BD). Baseline demographic, clinical and neurocognitive assessment scores were compared with those of 46 age and gender matched UHR subjects who did not transition to psychosis or BD over the follow-up period (UHR-NT) and 66 healthy comparison subjects. ResultsUHR-BD subjects had lower global functioning at baseline compared with UHR-NT subjects. There were no significant differences between UHR-BD and UHR-NT subjects on baseline demographic and neurocognitive characteristics. UHR-BD subjects had lower test performance than HC on picture completion, Trail-Making Tests and measures of global intelligence. LimitationsSmall sample size, limited and variable neurocognitive tests utilised and the confounding effects of psychotic symptoms might have impacted on the ability to detect meaningful clinical and neurocognitive differences. ConclusionsIn this exploratory study, neurocognition in young people who later develop BD is similar to those of subjects who are at a high risk for psychotic disorders, but there may be certain neurocognitive markers that distinguish this group from unaffected and healthy young people.

Longitudinal Study of Stressful Life Events and Daily Stressors Among Adolescents at High Risk for Psychotic Disorders

Psychosocial stress preceding the onset or recurrence of psychotic symptoms has been identified in patients with schizophrenia; yet there is limited understanding of the effects of stress in typically developing adolescents or those who show behavioral signs of risk for schizophrenia spectrum disorders. This study examined the developmental course of symptom progression as a function of stressful life events and daily hassles in adolescents with schizotypal personality disorder (SPD), other personality disorders, or no Axis II disorder. In this prospective longitudinal study, life events and daily stressors were assessed in adolescents aged 12 to 18 years. Results revealed that adolescents with SPD and other personality disorders reported significantly greater total, independent, and undesirable life events than individuals with no Axis II disorders. Youth with SPD report daily hassles to cause more distress compared to peers. Correlational analyses and hierarchal linear regression was used to evaluate the relationship of life events and daily stressors with psychiatric symptoms measured concurrently and 1 year later. Across diagnostic groups, the incidence of independent and undesirable life events were associated with current prodromal symptoms, while the frequency of daily stressors predicted a significant increment in positive, but not negative, prodromal symptoms over time. Therefore, adolescents who report greater daily stressors exhibit an increase in prodromal symptoms over a 1 year period. Psychosocial stress has been implicated in the etiology of schizophrenia, and these findings suggest the importance of life events and daily hassles as potential risk factors in the onset of psychotic symptoms during adolescence.

Treatment of Adolescents and Young Adults Experiencing Attenuated Psychotic Symptoms

Individuals, prior to the first psychotic episode, are symptomatic. Psychotic disorders in many cases develop gradually with a prolonged period of attenuated psychotic symptoms during which conventional criteria of DSM–IV disorders are not met. Young people are often not coping well with their symptom load. Because most of the disability which occurs in psychotic illness is entrenched during this phase, it is vital to explore the need of intervention prior to a first episode of psychosis. This article describes the development of the Personal Assessment and Crisis Evaluation (PACE) clinic in Melbourne, Australia. PACE is in unique service devoted to the systematic treatment and research of adolescents and young adults at high risk of psychosis who suffer perceptual distortions, unusual thoughts, or disorganized speech. The article reviews studies on treatment interventions in the prepsychotic phase and provides principles for the clinical management of young people considered at high risk for psychotic disorders.