Elevated Risk For Psychosis Research Articles

Psychosis and urbanicity: a review of the recent literature from epidemiology to neurourbanism.

Purpose of reviewEpidemiological studies associate city living with an elevated psychosis risk. Urban (social/economic) stress and exposure to environmental toxins, pollution or disease agents have been proposed to underlie this association. This review provides an update on the recent evidence (May 2017 – November 2018).Recent findingsOf 647 screened studies, 17 on: urbanicity–psychosis associations in worldwide high, middle and low-income countries; explanatory mechanisms, including nature exposure, social and economic stressors and genetic risk; urbanicity effects on the brain and coping; and urbanicity and resources, were included. The reviewed evidence revealed complex patterns of urbanicity–psychosis associations with considerable international variation within Europe and between low, middle and high-income countries worldwide. Social and economic stressors (e.g. migration, ethnic density and economic deprivation), nature exposure and access to resources could only explain part of the urbanicity effects. Risk factors differed between countries and between affective and non-affective psychosis.SummaryUrbanicity–psychosis associations are heterogeneous and driven by multiple risk and protective factors that seem to act differently in different ethnic groups and countries. Interdisciplinary research combining approaches, for example from experimental neuroscience and epidemiology, are needed to unravel specific urban mechanisms that increase or decrease psychosis risk.

Pituitary volume in individuals at elevated risk for psychosis: A systematic review and meta-analysis

BackgroundPituitary volume (PV) abnormalities, representing one of several markers of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been observed in psychosis, with variable patterns across illness stages. Typically, enlargements characterise first-episode patients, with reductions observed in those with chronic illness relative to healthy controls. Findings in high-risk populations have been inconsistent, highlighting the need for an updated review of the evidence. MethodsWe searched PubMed, PsycINFO, and EMBASE for studies examining PV in high-risk [clinical high-risk (CHR), family history of psychosis (FHx), schizotypal personality disorder (SPD), and psychotic-experiences (PEs)] and healthy individuals. Random effects models were used to examine group differences in PV (Hedges g) with stratified analyses and meta-regression employed to investigate the effect of high-risk category, transition status, age, sex, and antipsychotic medication. ResultsTen studies, yielding 11 effect sizes, were eligible for inclusion. Overall, high-risk individuals had significantly larger PV relative to healthy controls (g = 0.16 [95% CI: 0.01 to 0.32] p = 0.04), despite showing a reduction in whole brain volume (g = −0.17, [95% CI. −0.30 to −0.03] p = 0.020). Individual sub-group analyses for CHR and FHx groups showed no significant differences relative to controls; however, larger PV increases characterised those who later transitioned to psychosis (g = 0.55, [95% CI. 0.06 to 1.04] p = 0.028). Larger effect sizes were positively associated with the proportion of high-risk individuals receiving antipsychotic medication. ConclusionsPV enlargements characterise high-risk individuals and are more pronounced among those who later develop psychosis. We provide recommendations for future studies.

Affective and physiological reactivity to emotional comments in individuals at elevated risk for psychosis

BackgroundIndividuals with schizophrenia are at increased risk of relapse when they live in highly critical (i.e., high expressed emotion; EE) family environments. It remains less clear, however, how individuals at elevated risk for a psychotic disorder react to the social stress of EE. Here we examined whether individuals at elevated risk for developing schizophrenia report greater subjective changes in affect and have increased physiological reactivity after hearing critical, praising and neutral comments. MethodMeasures of heart rate, heart rate variability, skin conductance, and self-reported affective ratings were used to assess differential responses to EE-type stimuli in 38 individuals at elevated-risk for psychosis and 38 low-risk controls. ResultsThe elevated-risk group and low-risk controls, did not differ in their initial affective and physiological reactivity to criticism. However, during the recovery period following the criticism, the elevated-risk group demonstrated greater heart rate activation. They also showed more sensitivity to praise. Although elevated-risk participants initially had higher baseline levels of negative affect and heart rate, following praise, these levels reduced and became indistinguishable from the levels of low-risk controls. ConclusionsThese findings suggest that at-risk individuals may have more difficulty recovering from criticism than their self-report data might suggest. They may also derive physiological and affective benefits from praise. Important clinical implications of these findings are discussed.

122. Convergent Brain Mechanisms in 22q11.2 Deletion Syndrome and Schizophrenia

22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant associated with greatly elevated risk for psychosis. The ENIGMA 22q11.2 Deletion Syndrome Working Group (22qWG) represents the largest neuroimaging consortium effort to study 22q11DS and its relationship to psychosis. Here, in conjunction with the ENIGMA Schizophrenia Working Group (SZWG), we investigated overlap between cortical, subcortical, and diffusion-tensor imaging (DTI) markers of 22q11DS and schizophrenia.

33.3 LEVELS OF AND IMPLICATIONS FOR PERSONAL STIGMA AND MENTAL HEALTH LITERACY IN RELATION TO PSYCHOSIS AMONG YOUNG PEOPLE WITH AND WITHOUT RISK OF DEVELOPING PSYCHOTIC DISORDER

BackgroundMuch anti-stigma work suggests that reducing stigma and improving mental health literacy could also improve access to care and support for people with psychotic disorders. This is important given that increasing help-seeking, especially during the early stages of psychosis could reduce the substantial delays to care experienced by people with psychotic disorders. Little is known about levels of personal stigma and mental health literacy among young people at-risk of psychotic disorders, whether there are differences between young people with and without elevated risk for psychosis and how this is associated with actual help-seeking for individuals at-risk of developing psychotic disorders.MethodsWe interviewed participants from two existing, ongoing prospective cohorts in the UK and in Brazil. Participants were initially recruited from primary schools. Both samples represent enriched community cohorts (including a greater than average proportion of young people at risk of developing psychotic disorders) in Greater London (n=407) and a similar cohort of young people in Brazil (n=1,500). Participants were presented a vignette depicting a young person with early psychosis symptoms and asked about: recognition of the disorder; intended help-seeking; beliefs about interventions and prevention, stigmatising attitudes and whether they knew someone with a similar problem. We also collected detailed clinical data on psychiatric symptoms (via SDQ [Strengths and Difficulties Questionnaire] in the UK and DAWBA [Development and Well-Being Assessment] in Brazil), presence of psychotic-like experiences, and use of mental health services and personal experiences of seeking support for a mental disorder.ResultsFindings on the relationship between personal stigma and mental health literacy in relation to psychotic disorders, intended help-seeking and actual mental health service use, will be presented among young people with and without risk of developing psychotic disorders in the UK and Brazil.DiscussionReducing personal stigma and improving mental health literacy among young people at risk of psychosis who do not yet use clinical services could be important for future help-seeking. Future research should investigate the impact of anti-stigma interventions among young people with and without risk of developing psychotic disorders and how this facilitates help-seeking and support for this vulnerable group.

33. STIGMA AND RECOVERY AMONG YOUNG PEOPLE AT RISK FOR PSYCHOSIS: NOVEL INSIGHTS FROM GLOBAL RESEARCH

Overall : The recognition that attenuated clinical symptoms and impaired functioning often precede the onset of psychotic disorders has led to potentially transformative early intervention strategies which could benefit individuals during the prodromal phase through clinical intervention. However, these efforts could present a double-edged sword whereby on one hand earlier treatment could improve symptoms and facilitate recovery, but on the other hand, it could also increase labeling and associated stigma. This set of presentations draws from a diverse set of countries and researcher backgrounds, including peer perspectives to enhance recovery. Our panelists present novel data to address the potential challenges of early intervention strategies and how a better understanding of the stigmatising beliefs and experiences among individuals during the earliest signs of psychotic disorder could improve early intervention efforts.Two presentations use new perspectives to evaluate the perceptions and impact of stigma among prospective cohorts of young people at elevated risk for psychosis. Lawrence Yang uses one of the largest known cohorts of clinical high-risk young people from a multi-site study in the USA to assess the impact of two types of stigma: stigma associated with symptoms and and stigma associated with labelling of the ‘high-risk for psychosis’ identification. Sara Evans-Lacko uses two unique prospective community cohorts of young people enriched for risk of psychotic disorder from Brazil and the UK and investigates the levels of personal stigma and mental health literacy in relation to psychosis among young people with and without high risk of developing psychotic disorder. She will then present new data on how this relates to intended help-seeking and actual mental health service use among those at-risk for psychotic disorder. Utilizing a different perspective based on changing medical terminology for at-risk states, Danny Koren explores the attributions made by individuals in the general population and mental health professionals when applying ‘attenuated pathology’ versus ‘compromised health’ labels to refer to at-risk psychosis states.

The cerebellum and learning of non-motor associations in individuals at clinical-high risk for psychosis.

The cerebello-thalamo-cortical circuit (CTCC) has been implicated in schizophrenia. However, this work has been limited to structural and functional networks, or behavior, and to date, has not been evaluated in clinical high-risk (CHR) youth, a group at elevated risk for psychosis. Here, we used an innovative learning paradigm known to activate the CTCC (while limiting potential motor confounds) to evaluate CHR and healthy control individuals during functional magnetic resonance imaging (fMRI). 20 CHR and 21 healthy control individuals performed a second-order rule learning task while undergoing fMRI. This was preceded and followed by the paradigm under dual-task conditions. In addition, all participants underwent structured clinical interviews to confirm a prodromal syndrome and assess symptom severity. The rate of learning did not differ between groups. However, the CHR group consistently performed more poorly under dual-task conditions, and exhibited a higher dual-task cost after learning. Further, learning rate in the CHR group was significantly associated with symptom severity. Both groups showed activation in regions of the CTCC. During early learning, the CHR group exhibited greater engagement of regions of the default mode network, suggesting that they were less able to engage the appropriate task positive networks. During late learning, there were qualitative differences wherein controls showed more prefrontal cortical activation. Higher order cognitive rule learning is related to symptom severity in CHR individuals. fMRI revealed that CHR individuals may not reliably disengage the default mode network, and during late learning high-risk youth may not engage the prefrontal cortex as extensively as controls.

Clinical psychopathology in youth at familial high risk for psychosis.

While the course of psychopathology has been explored from an index mental health diagnosis onwards, there are few detailed, prospective studies of the occurrence of clinical psychopathology in youth with familial risk for severe mental illnesses such as psychosis. We sought to describe the appearance of Axis I psychopathology in a unique sample of adolescents with a family history of schizophrenia (FHR). One hundred and sixty two first- and second-degree relatives (mean age 15.7 ± 3.6; range 8-25) of probands with schizophrenia or schizoaffective disorder were assessed at baseline and annual intervals for up to 3 years, focusing on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis I psychopathology. Fourteen individuals (8.6%) developed a psychotic disorder. One hundred and five subjects (65%) met criteria for an Axis I disorder over the course of the study, the most common of which was a depressive episode (40 subjects; 25%). Of the 148 individuals who did not develop psychosis, 91 (61%) had one or more Axis I disorders compared with 10/14 converters who had a comorbid Axis I disorder (71%). Ordered by increasing age of onset, diagnoses included cognitive and externalizing disorders, anxiety disorders, affective disorders, substance use disorders and psychotic disorders. In addition to an elevated risk of psychosis, young FHR relatives manifest a broad range of non-psychotic Axis I psychopathology in childhood and adolescence. This breadth of diagnoses has implications for the structure and function of mental health services for young people.

Ethnic Minority Status, Age-at-Immigration and Psychosis Risk in Rural Environments: Evidence From the SEPEA Study.

ObjectiveSeveral ethnic minority groups experience elevated rates of first-episode psychosis (FEP), but most studies have been conducted in urban settings. We investigated whether incidence varied by ethnicity, generation status, and age-at-immigration in a diverse, mixed rural, and urban setting.MethodWe identified 687 people, 16–35 years, with an ICD-10 diagnosis of FEP, presenting to Early Intervention Psychosis services in the East of England over 2 million person-years. We used multilevel Poisson regression to examine incidence variation by ethnicity, rural–urban setting, generation status, and age-at-immigration, adjusting for several confounders including age, sex, socioeconomic status, population density, and deprivation.ResultsPeople of black African (incidence rate ratio: 4.06; 95% confidence interval [CI]: 2.63–6.25), black Caribbean (4.63; 95% CI: 2.38–8.98) and Pakistani (2.31; 95% CI: 1.35–3.94) origins were at greatest FEP risk relative to the white British population, after multivariable adjustment. Non-British white migrants were not at increased FEP risk (1.00; 95% CI: 0.77–1.32). These patterns were independently present in rural and urban settings. For first-generation migrants, migration during childhood conferred greatest risk of psychotic disorders (2.20; 95% CI: 1.33–3.62).ConclusionsElevated psychosis risk in several visible minority groups could not be explained by differences in postmigratory socioeconomic disadvantage. These patterns were observed across rural and urban areas of our catchment, suggesting that elevated psychosis risk for some ethnic minority groups is not a result of selection processes influencing rural–urban living. Timing of exposure to migration during childhood, an important social and neurodevelopmental window, may also elevate risk.

Does social disadvantage explain the higher risk of psychosis in immigrants? results from the eugei study in london

Evidence indicates that migrant and ethnic minority groups have an elevated risk of psychosis in a number of countries. Social disadvantage is one of the hypotheses put forward to explain these findings. The aim of this study is to investigate main effects, association and synergism between social disadvantage and migration on odds of psychotic experiences. We collected information on social disadvantage and migration from 332 patients and from 301 controls recruited from the local population in South London. Two indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analyzed. We found evidence that the odds of reporting psychotic experience were higher in those who experienced social disadvantage in childhood (OR= 2.88, 95% CI 2.03-4.06), social disadvantage in adulthood (OR= 9.06, 95% CI 5.21–15.74) and migration (OR = 1.46, 95% CI 1.05–2.02). When both social disadvantage and migration were considered together, the association with psychosis was slightly higher for social disadvantage in childhood and migration (OR 3.46, 95% CI 2.12–5.62) and social disadvantage in adulthood and migration (OR 9.10, 95% CI 4.63-17.86). Migrant cases were not more likely than non-migrant cases to report social disadvantage (p = 0.71) and no evidence of an additive interaction between migration and social disadvantage was found (ICR 0.32 95% CI -4.04–4.69). Preliminary results support the hypothesis that the association between social disadvantage and psychosis is independent of migration status.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Erythrocyte glutathione levels as long-term predictor of transition to psychosis

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion ‘low erythrocyte GSH’ to the set of criteria used to identify individuals at risk of psychosis may be indicated.

Associations between Electrophysiological Evidence of Reward and Punishment-Based Learning and Psychotic Experiences and Social Anhedonia in At-Risk Groups

Both positive psychotic symptoms and anhedonia are associated with striatal functioning, but few studies have linked risk for psychotic disorders to a neural measure evoked during a striatal dopamine-related reward and punishment-based learning task, such as a reversal learning task (RLT; Cools et al, 2009). The feedback-related negativity (FRN) is a neural response that in part reflects striatal dopamine functioning. We recorded EEG during the RLT in three groups: (a) people with psychotic experiences (PE; n=20) at increased risk for psychotic disorders; (b) people with extremely elevated social anhedonia (SocAnh; n=22); and (c) controls (n=20). Behaviorally, consistent with increased striatal dopamine, the PE group exhibited better behavioral learning (ie, faster responses) after unexpected reward than after unexpected punishment. Moreover, although the control and SocAnh groups showed a larger FRN to punishment than reward, the PE group showed similar FRNs to punishment and reward, with a numerically larger FRN to reward than punishment (with similar results on these trials also found for a P3a component). These results are among the first to link a neural response evoked by a reward and punishment-based learning task specifically with elevated psychosis risk.

Vitamin D deficiency, behavioral atypicality, anxiety and depression in children with chromosome 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex developmental disorder with serious medical, cognitive and emotional symptoms across the lifespan. This genetic deletion also imparts a lifetime risk for developing schizophrenia that is 25-30 times that of the general population. The origin of this risk is multifactorial and may include dysregulation of the stress response and immunological systems in relation to brain development. Vitamin D is involved in brain development and neuroprotection, gene transcription, immunological regulation and influences neuronal signal transduction. Low levels of vitamin D are associated with schizophrenia, depression and anxiety in the general population. Yet, little is known about how vitamin D levels in children with 22q11.2DS could mediate risk of psychosis in adulthood. Blood plasma levels of vitamin D were measured in children aged 7-16 years with (n=11) and without (n=16) 22q11.2DS in relation to parent reports of children's anxiety and atypicality. Anxiety and atypicality in childhood are risk indicators for the development of schizophrenia in those with 22q11.2DS and the general population. Children with 22q11.2DS had lower vitamin D levels, as well as elevated anxiety and atypicality compared with typical peers. Higher levels of anxiety, depression and internalizing problems but not atypicality were associated with lower levels of vitamin D. Vitamin D insufficiency may relate to higher levels of anxiety and depression, in turn contributing to the elevated risk of psychosis in this population. Further study is required to determine casual linkages between anxiety, stress, mood and vitamin D in children with 22q11.2DS.

Ethnic enclaves and risk of psychiatric disorders among first- and second-generation immigrants in Sweden

Some non-Western immigrant groups in Europe have elevated risk of psychosis relative to native-born. It is hypothesized that neighborhood ethnic density moderates this risk. Immigration to Sweden has increased substantially recently, particularly from the Middle East. This study examined the relationship between neighborhood ethnic density (i.e., living in an immigrant enclave) and risk of psychotic and affective disorders among three groups: Iraqi immigrants, immigrants from other nations, and native-born Swedes. Individuals aged 15-60, without prevalent psychopathology, were drawn from Swedish population-based registries and followed from 2005 to 2010 (N = 950,979). Multi-level logistic regression was used to examine the association between neighborhood ethnic composition and incident psychopathology. Cumulative incidence of psychopathology was greater in Iraqi enclaves relative to predominantly Swedish neighborhoods (6.3 vs. 4.5%). Iraqis living in enclaves did not have significantly greater risk of psychosis (Odds Ratio (OR): 1.66, 95% Confidence Interval (CI) 0.92-2.97) or affective disorders (OR: 1.04, 95%CI 0.85-1.27) relative to those in predominantly Swedish neighborhoods. There was no increased risk of psychosis (OR: 0.93, p > 0.05) or affective disorders (OR: 0.93, p > 0.05) for other immigrants living in an enclave. Swedes living in an enclave had elevated risk of both psychosis (OR: 1.37, p < 0.05) and affective disorders (OR: 1.14, p < 0.05) relative to those in predominantly Swedish neighborhoods. Second-generation Iraqis had higher risk of psychotic but not affective disorders relative to first-generation. Neighborhood ethnic density does not moderate risk of psychopathology for immigrants in Sweden. Findings regarding Swedes are consistent with social drift.

Hemispheric language asymmetry in first episode psychosis and schizotypy: the role of cannabis consumption and cognitive disorganization.

Cannabis use has been related to an elevated psychosis risk and attenuated cognitive functioning. Cannabis-related cognitive impairments are also observed in populations along the psychosis dimension. We here investigated whether a potential behavioral marker of the psychosis dimension (attenuated functional hemispheric asymmetry) is even further attenuated in individuals using cannabis (CU) vs those not using cannabis (nCU). We tested 29 patients with first-episode psychosis (FEP; 11 CU) and 90 healthy controls (38 CU) on lateralized lexical decisions assessing left-hemisphere language dominance. In patients, psychotic symptoms were assessed by Positive & Negative Symptom Scale (PANSS). In controls, self-reported schizotypy was assessed (The Oxford-Liverpool Inventory of Feelings and Experiences: O-LIFE). Results indicated that nCU FEP patients had a relative reduced hemispheric asymmetry, as did controls with increasing cognitive disorganization (CogDis) scores, in particular when belonging to the group of nCU controls. Positive, disorganized and negative PANSS scores in patients and negative and positive schizotypy in controls were unrelated to hemispheric asymmetry. These findings suggest that cannabis use potentially balances rather than exacerbates uncommon hemispheric laterality patterns. Moreover, in healthy populations, the potential stabilization of typical hemispheric asymmetry in CU might be most relevant to individuals with elevated CogDis. We discuss the potential beneficial and harmful effects of cannabis use along the psychosis dimension together with propositions for future studies that should account for the mediating role of additional substances (eg nicotine), cannabis composition (eg cannabidiol content), and individual differences (eg physical health, or absence of significant polysubstance use).

Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project.

Introduction: A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions. Methods: The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A “greedy algorithm” selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40). Results: The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis. Conclusion: If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.

Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: relationship to psychosocial stress and cognition.

SummaryAbnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9–12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11–14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size = −0.73, p = 0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset.

Informed consent in the psychosis prodrome: ethical, procedural and cultural considerations.

Research focused on the prodromal period prior to the onset of psychosis is essential for the further development of strategies for early detection, early intervention, and disease pre-emption. Such efforts necessarily require the enrollment of individuals who are at risk of psychosis but have not yet developed a psychotic illness into research and treatment protocols. This work is becoming increasingly internationalized, which warrants special consideration of cultural differences in conceptualization of mental illness and international differences in health care practices and rights regarding research participation. The process of identifying and requesting informed consent from individuals at elevated risk for psychosis requires thoughtful communication about illness risk and often involves the participation of family members. Empirical studies of risk reasoning and decisional capacity in young people and individuals with psychosis suggest that most individuals who are at-risk for psychosis can adequately provide informed consent; however ongoing improvements to tools and procedures are important to ensure that this work proceeds with maximal consideration of relevant ethical issues. This review provides a discussion of these issues in the context of international research efforts.

Blood Biomarkers Could Aid Prediction of Psychosis Risk

Blood Biomarkers Could Aid Prediction of Psychosis Risk

Hippocampal volume reduction in chromosome 22q11.2 deletion syndrome (22q11.2DS): A longitudinal study of morphometry and symptomatology

Recent studies observed an association between the structural integrity of the hippocampal structure and the manifestations of clinically significant psychotic symptoms in participants at high risk for psychosis. The present study sought to investigate the longitudinal trajectory of the hippocampal volume and its subregions among a sample of participants affected by 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic disorder associated with elevated risk for psychosis. We specifically investigated possible correlations between hippocampal volumes, as measured by magnetic resonance imaging (MRI), and the manifestation of positive psychotic symptoms (hallucinations and delusions). Regional hippocampal volumes were measured twice with cerebral MRI obtained at 3-year intervals in 30 healthy participants and 31 gender-matched 22q11.2 microdeletion carriers aged 6 to 22. We examined potential associations between psychotic symptom manifestations and volumetric parameters at both time points. We found a hippocampal body-driven significant reduction in hippocampal volume among patients with 22q11DS compared to controls. No significant group by time interaction for the total or the subregional volumes were observed. In patients, larger hippocampal head at baseline was associated with the presence of hallucinations at follow-up. We first discuss the reduced hippocampal body finding in light of potentially abnormal mesiocortical circuits. We further discuss the association between baseline hippocampal head volume in participants with 22q11DS as a possible marker related to the later unfolding of psychotic symptoms.