At risk or not at risk? A meta‐analysis of the prognostic accuracy of psychometric interviews for psychosis prediction

An accurate detection of individuals at clinical high risk (CHR) for psychosis is a prerequisite for effective preventive interventions. Several psychometric interviews are available, but their prognostic accuracy is unknown. We conducted a prognostic accuracy meta‐analysis of psychometric interviews used to examine referrals to high risk services. The index test was an established CHR psychometric instrument used to identify subjects with and without CHR (CHR+ and CHR?). The reference index was psychosis onset over time in both CHR+ and CHR? subjects. Data were analyzed with MIDAS (STATA13). Area under the curve (AUC), summary receiver operating characteristic curves, quality assessment, likelihood ratios, Fagan's nomogram and probability modified plots were computed. Eleven independent studies were included, with a total of 2,519 help‐seeking, predominately adult subjects (CHR+: N=1,359; CHR?: N=1,160) referred to high risk services. The mean follow‐up duration was 38 months. The AUC was excellent (0.90; 95% CI: 0.87‐0.93), and comparable to other tests in preventive medicine, suggesting clinical utility in subjects referred to high risk services. Meta‐regression analyses revealed an effect for exposure to antipsychotics and no effects for type of instrument, age, gender, follow‐up time, sample size, quality assessment, proportion of CHR+ subjects in the total sample. Fagan's nomogram indicated a low positive predictive value (5.74%) in the general non‐help‐seeking population. Albeit the clear need to further improve prediction of psychosis, these findings support the use of psychometric prognostic interviews for CHR as clinical tools for an indicated prevention in subjects seeking help at high risk services worldwide.     

Neuropsychological Impairment in Prodromal,First-Episode,and Chronic Psychosis: Assessing RBANS Performance

BackgroundCognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis.MethodWe administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis.ResultsPerformance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis.ConclusionsCognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease.     

Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio‐economic development of the country or the specific health care system.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and es­timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.     

Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China

Background and Aims

Given the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents.

Methods

A sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up.

Results

CHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome.

Conclusions

This study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals.     

From Epidemiology to Daily Life: Linking Daily Life Stress Reactivity to Persistence of Psychotic Experiences in a Longitudinal General Population Study

Subclinical psychotic experiences at the level of the general population are common, forming an extended psychosis phenotype with clinical psychosis. Persistence of subclinical experiences is associated with transition to later mental disorder. Increased daily life stress reactivity is considered an endophenotype for psychotic disorders. We examined, in a longitudinal framework, whether baseline momentary assessment markers of stress reactivity would predict persistence of subclinical psychotic experiences over time. In a general population sample of female twins (N = 566), the Experience Sampling Method (ESM; repetitive random sampling of momentary emotions, psychotic experiences and context) was used to assess (emotional and psychotic) daily life stress reactivity. Persistence of subclinical psychotic experiences was based on the Community Assessment of Psychic Experiences (CAPE), assessed three times over 14 months post-baseline. It was investigated whether baseline daily life emotional and psychotic stress reactivity predicted persistence of psychotic experiences over time. Higher levels of emotional stress reactivity (a decrease in positive and an increase in negative affect in response to stress), and increased psychotic reactivity to daily stress was found in individuals with persistent psychotic experiences over time compared to individuals with transient psychotic experiences. The results suggest that markers of daily life stress reactivity may predict “macro-level” persistence of normally transient expression of psychotic liability over time. Linking daily life markers of altered reactivity in terms of emotions and psychotic experiences to longitudinal persistence of psychotic experiences, associated with increased risk of transition to overt mental disorder, may contribute to earlier and more accurate diagnosis of risk.     

Psychosis as a transdiagnostic and extended phenotype in the general population

A large body of research indicates that weak expressions of positive psychotic symptoms (“psychotic experiences”) can be measured in the general population, and likely represent the behavioural manifestation of distributed multifactorial (genetic and non‐genetic) risk for psychosis. Psychotic experiences are a transdiagnostic phenomenon: the majority of individuals with these experiences have a diagnosis of non‐psychotic disorder, particularly common mental disorder, in which psychotic experiences predict greater illness severity and poorer treatment response. Some of the people with common mental disorder and psychotic experiences will present to mental health services meeting criteria for “clinical high risk”. Treatment of the transdiagnostic dimension of psychosis in individuals with common mental disorder who meet “clinical high risk” criteria thus may improve outcome (which cannot be interpreted as prevention of “schizophrenia”). Subthreshold psychotic experiences are transitory in about 80% of individuals, while around 20% go on to develop persistent psychotic experiences and 7% a psychotic disorder, with an annual transition rate of 0.5‐1%. Persistence is associated, on the one hand, with environmental exposures, particularly childhood trauma, and, on the other, with network‐type dynamic interactions between psychotic experiences themselves (e.g., interactions between hallucinatory experiences and delusional ideation) and between symptom dimensions (e.g., interactions between affective symptoms and psychotic experiences, or interactions between subthreshold negative symptoms and psychotic experiences). The study of psychotic experiences is helping to elucidate the mechanisms by which environmental and genetic influences shape the transdiagnostic expression of psychosis proneness, that is mostly transitory but may first become persistent over time and eventually give rise to transition to a psychotic disorder.     

Early Intervention in Psychosis: A Case Study on Normal and Pathological

Accumulating evidence suggests that delays in receiving treatment are associated with poorer prognosis and longer periods of unneeded suffering. The duration of untreated psychosis (DUP) is considered to be one of the most important determinants of outcome in the first episode of psychosis. However, the focus on decreasing the length of untreated illness tends to overlook the difficult task of making sense of psychotic experiences during a first episode. Using a qualitative analysis of narratives obtained from interviews with an individual and her husband, we examine what delayed her seeking help, how she became convinced that she needed treatment and what this meant for her and her husband. Additionally, we look at the five-year development of both a literal and a figurative space within which both the subject and her husband came to utilize, whether consciously or unconsciously, the ‘stories’ of her psychotic experiences to construct a shared and even ‘safe’ and familiar means of spousal connection. The exploration of this shared space reveals the normative and moral values embedded in the concept of DUP and suggests alternative ways of understanding the help-seeking behaviors in early psychosis.     

Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: a prospective two‐year follow‐up

Prospective evaluation of youths with early psychotic‐like experiences can enrich our knowledge of clinical, biobehavioral and environmental risk and protective factors associated with the development of psychotic disorders. We aimed to investigate the predictors of persistence or worsening of psychosis spectrum features among US youth through the first large systematic study to evaluate subclinical symptoms in the community. Based on Time 1 screen of 9,498 youth (age 8‐21) from the Philadelphia Neurodevelopmental Cohort, a subsample of participants was enrolled based on the presence (N=249) or absence (N=254) of baseline psychosis spectrum symptoms, prior participation in neuroimaging, and current neuroimaging eligibility. They were invited to participate in a Time 2 assessment two years on average following Time 1. Participants were administered the Structured Interview for Prodromal Syndromes, conducted blind to initial screen status, along with the Schizotypal Personality Questionnaire and other clinical measures, computerized neurocognitive testing, and neuroimaging. Clinical and demographic predictors of symptom persistence were examined using logistic regression. At Time 2, psychosis spectrum features persisted or worsened in 51.4% of youths. Symptom persistence was predicted by higher severity of subclinical psychosis, lower global functioning, and prior psychiatric medication at baseline. Youths classified as having psychosis spectrum symptoms at baseline but not at follow‐up nonetheless exhibited comparatively higher symptom levels and lower functioning at both baseline and follow‐up than typically developing youths. In addition, psychosis spectrum features emerged in a small number of young people who previously had not reported significant symptoms but who had exhibited early clinical warning signs. Together, our findings indicate that varying courses of psychosis spectrum symptoms are evident early in US youth, supporting the importance of investigating psychosis risk as a dynamic developmental process. Neurocognition, brain structure and function, and genomics may be integrated with clinical data to provide early indices of symptom persistence and worsening in youths at risk for psychosis.     

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample

Background

There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.

Methods

We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.

Results

Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Conclusion

The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.     

Childhood Psychosis or Mental Retardation: A Diagnostic Dilemma: I. Psychiatric and Psychological Aspects

A relatively large percentage of children seen at a mental retardation clinic demonstrated psychotic symptoms. The entire group with psychotic manifestations, 62 in all, were reviewed in order to clarify the diagnosis of childhood psychosis or mental retardation. The 1961 British criteria for childhood psychosis were used and are advocated by the authors. Childhood psychosis was the primary diagnosis in 38 cases, and psychosis secondary to brain damage in 24 cases. Onset of the condition under the age of three years and a poor prognosis for social recovery were characteristic of the entire group.Obvious emotional disorder was present in 21 mothers and 14 fathers. There was a continuum in terms of number of psychotic symptoms, level of intelligence and presence of organic signs. It is concluded that there is an overlap between the entities of childhood psychosis and mental retardation.     

Pathways to Care: Duration of Untreated Psychosis from Karachi,Pakistan

Background

Substantial amount of time is lost before initiation of treatment in Schizophrenia. The delay in treatment is labelled as Duration of Untreated Psychosis (DUP). Most of these estimates come from western countries, where health systems are relatively better developed. There is dearth of information on pathway to care from developing countries.

Methods and Results

Patients with ICD-10 based diagnosis of Schizophrenia were enrolled by convenient method of sampling. The pathway to care was explored through a semi-structured questionnaire. Onset, course and symptoms of psychosis were assessed using Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS). Ethical approval of the project was taken from The Aga Khan University, Ethics Review Committee. Of the enrolled 93 subjects, 55 (59%) were males and 38 (41%) were females. In our sample, 1.56 mean (median, 2) attempts were made prior to successful help seeking. The duration of untreated psychosis was 14.8 months (St. Deviation; 29.4). DUP was 16.8 months (St. Deviation; 34.9) for males and 11.8 months (St. Deviation; 18.9) for females. In the pathway to care, psychiatrists featured prominently as initial care providers. In the first attempt at help-seeking, 43% patients were initially taken to psychiatrists. After the initial consultation, 45% were prescribed psychotropic medication while 7% were hospitalized. Only 9% subjects were given the diagnosis of schizophrenia initially. When participants were inquired about the reasons for delay, 29% reported financial difficulties as the barrier to care. Positive symptoms of psychosis were present in 57% subjects while negative symptoms were present in 30% subjects. There was a statistically significant difference (Chi-square; 7.928, df: 1, Sig 0.005) between DUP and the positive and negative symptoms category.

Conclusion

In the absence of well developed primary care health system in Pakistan, majority of patients present to psychiatrists as a first contact. DUP, as a measurement of help seeking behaviour, tends to be shorter with positive symptoms of Schizophrenia. Substantial amount of time is lost due to non recognition of disease and subsequently, inadequate treatment. Secondary prevention strategies should focus on families, which play an important role in the treatment-seeking process of psychotic patients.     

Cortical Morphology Differences in Subjects at Increased Vulnerability for Developing a Psychotic Disorder: A Comparison between Subjects with Ultra-High Risk and 22q11.2 Deletion Syndrome

IntroductionSubjects with 22q11.2 deletion syndrome (22q11DS) and subjects with ultra-high risk for psychosis (UHR) share a risk of approximately 30% to develop a psychotic disorder. Studying these groups helps identify biological markers of pathophysiological processes involved in the development of psychosis. Total cortical surface area (cSA), total cortical grey matter volume (cGMV), cortical thickness (CT), and local gyrification index (LGI) of the cortical structure have a distinct neurodevelopmental origin making them important target markers to study in relation to the development of psychosis.Results22q11DS subjects had lower total cSA and total cGMV compared to UHR and HC subjects. The 22q11DS subjects showed bilateral lower LGI in the i) prefrontal cortex, ii) precuneus, iii) precentral gyrus and iv) cuneus compared to UHR subjects. Additionally, lower LGI was found in the left i) fusiform gyrus and right i) pars opercularis, ii) superior, and iii) inferior temporal gyrus in 22q11DS subjects compared to HC. In comparison to 22q11DS subjects, the UHR subjects had lower CT of the insula. For both risk groups, positive symptom severity was negatively correlated to rostral middle frontal gyrus CT.ConclusionA shared negative correlation between positive symptom severity and rostral middle frontal gyrus CT in UHR and 22q11DS may be related to their increased vulnerability to develop a psychotic disorder. 22q11DS subjects were characterised by widespread lower degree of cortical gyrification linked to early and postnatal neurodevelopmental pathology. No implications for early neurodevelopmental pathology were found for the UHR subjects, although they did have distinctively lower insula CT which may have arisen from defective pruning processes during adolescence. Implications of these findings in relation to development of psychotic disorders are in need of further investigation in longitudinal studies.     

Neuroanatomical correlates of suicide in psychosis: the possible role of von Economo neurons

Suicide is the most important incident in psychiatric disorders. Psychological pain and empathy to pain involves a neural network that involves the anterior cingulate cortex (ACC) and the anterior insula (AI). At the neuronal level, little is known about how complex emotions such as shame, guilt, self-derogation and social isolation, all of which feature suicidal behavior, are represented in the brain. Based on the observation that the ACC and the AI contain a large spindle-shaped cell type, referred to as von Economo neuron (VEN), which has dramatically increased in density during human evolution, and on growing evidence that VENs play a role in the pathophysiology of various neuropsychiatric disorders, including autism, psychosis and dementia, we examined the density of VENs in the ACC of suicide victims. The density of VENs was determined using cresyl violet-stained sections of the ACC of 39 individuals with psychosis (20 cases with schizophrenia, 19 with bipolar disorder). Nine subjects had died from suicide. Twenty specimen were available from the right, 19 from the left ACC. The density of VENs was significantly greater in the ACC of suicide victims with psychotic disorders compared with psychotic individuals who died from other causes. This effect was restricted to the right ACC. VEN density in the ACC seems to be increased in suicide victims with psychosis. This finding may support the assumption that VEN have a special role in emotion processing and self-evaluation, including negative self-appraisal.     

Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.     

Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: 18F-Fallypride Positron Emission Tomography Study

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and ¹⁸F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ⁹-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ⁹-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in ¹⁸F-fallypride displacement. Voxel-based statistical maps, representing specific D_2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ⁹-THC administration, reflecting dopamine release. While Δ⁹-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ⁹-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ⁹-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.     

Short Association Fibres of the Insula-Temporoparietal Junction in Early Psychosis: A Diffusion Tensor Imaging Study

Evidence shows that there are reductions in gray matter volume (GMV) and changes in long association white matter fibres within the left insula-temporoparietal junction (TPJ) during the early stages of psychotic disorders but less is known about short association fibres (sAFs). In this study we sought to characterise the changes in sAFs and associated volumetric changes of the left insula-TPJ during the early stages of psychosis. Magnetic resonance imaging was obtained from a sample of young people with psychosis (n = 42) and healthy controls (n = 45), and cortical parcellations of the left insula-TPJ were used as seeding masks to reconstruct 13 sAFs. Compared to healthy counterparts, the psychosis group showed significant reductions in fractional anisotropy (FA) in the sAFs connecting the superior (STG) and middle temporal gyri (MTG) and as well as reduced GMV within the inferior temporal gyrus and increased white matter volume (WMV) within Heschl''s gyrus (HG). Furthermore, adolescent-onset psychosis subjects (onset 18 year or earlier) showed FA reductions in the STG-HG sAF when compared to adult-onset subjects, but this was not associated with changes in GMV nor WMV of the STG or HG. These findings suggest that during the early stages of psychosis, changes in sAFs and associated cortical GMV and WMV appear to occur independently, however age of onset of a psychotic syndrome/disorder influences the pattern of neuroanatomical abnormalities.