Neurocognition in the Extended Psychosis Phenotype: Performance of a Community Sample of Adolescents With Psychotic Symptoms on the MATRICS Neurocognitive Battery

Neurocognitive dysfunction is well established in psychosis, but recent work suggests that processing speed deficits might represent a particularly important cognitive deficit. A number of significant confounds, however, such as disease chronicity and antipsychotic medication use, have been shown to affect processing speed, causing debate as to the core cognitive features of psychosis. We adopted a novel strategy of testing neurocognitive performance in the “extended psychosis phenotype,” involving community-based adolescents who are not clinically psychotic but who report psychotic symptoms and who are at increased risk of psychosis in adulthood. This allows investigation of the earliest cognitive factors associated with psychosis risk, while excluding potential confounds such as disease chronicity and antipsychotic use. A population sample of 212 school-going adolescents aged 11–13 years took part in this study. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Neurocognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus neurocognitive battery. Adolescents with psychotic symptoms performed significantly more poorly on 3 processing speed tasks: Trail Making Test-A (F = 3.3, P < .05), Trail Making Test-B (F = 3.1, P < .05), and digit symbol coding task (F = 7.0, P < .001)—as well as on a nonverbal working memory (spatial span) task (F = 3.2, P < .05). Our findings support the idea that neurocognitive impairment, and processing speed impairment in particular, is a core feature of psychosis risk. This group likely demonstrates some of the earliest cognitive impairments associated with psychosis vulnerability.Key words: epidemiology/adolescents/cognitionKey words: epidemiology, adolescents, cognition     

Personality Compensates for Impaired Quality of Life and Social Functioning in Patients With Psychotic Disorders Who Experienced Traumatic Events

Background: Patients with psychotic disorders who experienced childhood trauma show more social dysfunction than patients without traumatic experiences. However, this may not hold for all patients with traumatic experiences. Little is known about the potential compensating role of Five-Factor Model personality traits within this group, despite their strong predictive value for social functioning and well-being in the general population. Methods: Our sample consisted of 195 patients with psychotic disorders (74% diagnosed with schizophrenia) and 132 controls. Cluster analyses were conducted to identify and validate distinct personality profiles. General linear model analyses were conducted to examine whether patients with different profiles differed in social functioning and quality of life (QoL), while controlling for possible confounders. Mediation models were tested to assess potential causal links. Results: In general, patients with higher levels of self-reported traumatic experiences (PT+) showed lower QoL and more social withdrawal compared with patients with lower traumatic experiences (PT−). Two clusters reflecting personality profiles were identified. PT+ with the first profile (lower neuroticism and higher extraversion, openness, agreeableness, and conscientiousness) presented higher levels of QoL and better social functioning in several areas, including less withdrawal, compared with both PT+ and PT− with the second profile. PT+ and PT− with the first personality profile did not differ in QoL and social functioning. Mediation analyses suggested that personality traits mediate the relation between traumatic experiences and QoL and social withdrawal. Conclusions: Our findings indicate that personality may “buffer” the impact of childhood traumatic experiences on functional outcome in patients with psychotic disorders.Key words: Five-Factor Model, psychosis, trauma, well-being, resilience     

Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age

Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRS_SCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = −0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRS_SCZ. Taken together, our findings indicate that cognitive biomarkers—“top-down inhibition” impairments in particular—may be of critical importance as indicators of psychosis vulnerability.     

Cognitive Biases Questionnaire for Psychosis

Objective:

The Cognitive Biases Questionnaire for psychosis (CBQp) was developed to capture 5 cognitive distortions (jumping to conclusions, intentionalising, catastrophising, emotional reasoning, and dichotomous thinking), which are considered important for the pathogenesis of psychosis. Vignettes were adapted from the Cognitive Style Test (CST),¹ relating to “Anomalous Perceptions” and “Threatening Events” themes.

Method:

Scale structure, reliability, and validity were investigated in a psychosis group, and CBQp scores were compared with those of depressed and healthy control samples.

Results:

The CBQp showed good internal consistency and test-retest reliability. The 5 biases were not independent, with a 2-related factor scale providing the best fit. This structure suggests that the CBQp assesses a general thinking bias rather than distinct cognitive errors, while Anomalous Perception and Threatening Events theme scores can be used separately. Total CBQp scores showed good convergent validity with the CST, but individual biases were not related to existing tasks purporting to assess similar reasoning biases. Psychotic and depressed populations scored higher than healthy controls, and symptomatic psychosis patients scored higher than their nonsymptomatic counterparts, with modest relationships between CBQp scores and symptom severity once emotional disorders were partialled out. Anomalous Perception theme and Intentionalising bias scores showed some specificity to psychosis.

Conclusions:

Overall, the CBQp has good psychometric properties, although it is likely that it measures a different construct to existing tasks, tentatively suggested to represent a bias of interpretation rather than reasoning, judgment or decision-making processes. It is a potentially useful tool in both research and clinical arenas.Key words: schizophrenia, thinking errors, delusions, hallucinations, cognitive behavior therapy for psychosis     

Neuroanatomical Maps of Psychosis Onset: Voxel-wise Meta-Analysis of Antipsychotic-Naive VBM Studies

Background: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Methods: Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and “signed differential mapping” voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Results: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Conclusions: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.     

Prevalence and Clinical Significance of DSM-5–Attenuated Psychosis Syndrome in Adolescents and Young Adults in the General Population: The Bern Epidemiological At-Risk (BEAR) Study

Objective: Section III of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists attenuated psychosis syndrome as a condition for further study. One important question is its prevalence and clinical significance in the general population. Method: Analyses involved 1229 participants (age 16–40 years) from the general population of Canton Bern, Switzerland, enrolled from June 2011 to July 2012. “Symptom,” “onset/worsening,” “frequency,” and “distress/disability” criteria of attenuated psychosis syndrome were assessed using the structured interview for psychosis-risk syndromes. Furthermore, help-seeking, psychosocial functioning, and current nonpsychotic axis I disorders were surveyed. Well-trained psychologists performed assessments using the computer-assisted telephone interviewing technique. Results: The symptom criterion was met by 12.9% of participants, onset/worsening by 1.1%, frequency by 3.8%, and distress/disability by 7.0%. Symptom, frequency, and distress/disability were met by 3.2%. Excluding trait-like attenuated psychotic symptoms (APS) decreased the prevalence to 2.6%, while adding onset/worsening reduced it to 0.3%. APS were associated with functional impairments, current mental disorders, and help-seeking although they were not a reason for help-seeking. These associations were weaker for attenuated psychosis syndrome. Conclusions: At the population level, only 0.3% met current attenuated psychosis syndrome criteria. Particularly, the onset/worsening criterion, originally included to increase the likelihood of progression to psychosis, lowered its prevalence. Because progression is not required for a self-contained syndrome, a revision of the restrictive onset criterion is proposed to avoid the exclusion of 2.3% of persons who experience and are distressed by APS from mental health care. Secondary analyses suggest that a revised syndrome would also possess higher clinical significance than the current syndrome.Key words: attenuated psychosis syndrome, general population, prevalence, distress, disability, functional impairment     

Neural and Behavioral Correlates of Aberrant Salience in Individuals at Risk for Psychosis

The “aberrant salience” model proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to the attribution of significance to stimuli that would normally be considered irrelevant. This is thought to occur during the prodromal phase of psychotic disorders, but this prediction has not been tested previously. In the present study, we tested this model in 18 healthy volunteers and 18 unmedicated individuals at ultra-high risk of psychosis. Subjects performed the Salience Attribution Test, which provides behavioral measures of adaptive and aberrant motivational salience, during functional magnetic resonance imaging to assess neural responses to relevant and irrelevant stimulus features. On a separate occasion, the same subjects were also studied with [¹⁸F]fluorodopa positron emission tomography to measure dopamine synthesis capacity. Individuals at ultra-high risk of psychosis were more likely to attribute motivational salience to irrelevant stimulus features (t(26.7) = 2.8, P = .008), and this bias was related to the severity of their delusion-like symptoms (r = .62, P = .008). Ventral striatal responses to irrelevant stimulus features were also correlated with delusion-like symptoms in the ultra-high risk group (r = .59, P = .017). Striatal dopamine synthesis capacity correlated negatively with hippocampal responses to irrelevant stimulus features in ultra-high risk individuals, but this relationship was positive in controls. These data are consistent with the hypothesis that aberrant salience processing underlies psychotic symptoms and involves functional alterations in the striatum, hippocampus, and the subcortical dopamine system.Key words: psychosis, aberrant salience, salience attribution test, functional magnetic resonance imaging, positron emission tomography, dopamine     

Self-reported psychosis-like symptoms and the continuum of psychosis

Background: It has been suggested that psychotic symptoms may be distributed along a continuum that extends from normality through depressive states to schizophrenia with increasing level of severity. This study examined the hypothesis that the severity of positive psychotic symptoms increases from normality, through depression/anxiety states to clinical psychosis. Methods: Consecutive general practice attenders completed a self-report questionnaire of 24 items of delusional ideation and hallucinatory experiences and the GHQ-12. The following groups were compared: (1) subjects with a diagnosis of psychosis (n = 57), (2) GHQ cases (n = 245), and (3) GHQ non-cases (n = 378). Results: Quantitative differences were apparent in the great majority of items on delusional ideation and hallucinatory experiences, in that normals scored lowest, psychosis patients scored highest and GHQ cases scored in between. This pattern of differences was apparent for all dimensions of psychosis-like experiences, including the more “schizophrenic” ones, with the exception of Grandiosity (GHQ cases similar to normals) and Paranormal Beliefs (no differences between the three groups). Conclusions: Similar to findings in aetiological research, phenotypic differences between normal controls, patients with anxiety/depression and patients with psychosis appear quantitative rather than qualitative for core dimensions of psychosis. Accepted: 15 June 1999     

The Epidemiology and Associated Phenomenology of Formal Thought Disorder: A Systematic Review

Background: Authors of the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) have recommended to “integrate dimensions into clinical practice.” The epidemiology and associated phenomenology of formal thought disorder (FTD) have been described but not reviewed. We aimed to carry out a systematic review of FTD to this end. Methods: A systematic review of FTD literature, from 1978 to 2013, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 881 abstracts were reviewed and 120 articles met inclusion criteria; articles describing FTD factor structure (n = 15), prevalence and longitudinal course (n = 41), role in diagnosis (n = 22), associated clinical variables (n = 56), and influence on outcome (n = 35) were included. Prevalence estimates for FTD in psychosis range from 5% to 91%. Dividing FTD into domains, by factor analysis, can accurately identify 91% of psychotic diagnoses. FTD is associated with increased clinical severity. Poorer outcomes are predicted by negative thought disorder, more so than the typical construct of “disorganized speech.” Conclusion: FTD is a common symptom of psychosis and may be considered a marker of illness severity. Detailed dimensional assessment of FTD can clarify diagnosis and may help predict prognosis.Key words: formal thought disorder, thought disorder, phenomenology, epidemiology, prognosis, psychosis, schizophrenia, language, communication     

Sexual Trauma Increases the Risk of Developing Psychosis in an Ultra High-Risk “Prodromal” Population

Studies indicate a high prevalence of childhood trauma in patient cohorts with established psychotic disorder and in those at risk of developing psychosis. A causal link between childhood trauma and development of psychosis has been proposed. We aimed to examine the association between experience of childhood trauma and the development of a psychotic disorder in a large “Ultra High Risk” (UHR) for psychosis cohort. The data were collected as part of a longitudinal cohort study of all UHR patients recruited to research studies at the Personal Assessment and Clinical Evaluation clinic between 1993 and 2006. Baseline data were collected at recruitment to these studies. The participants completed a comprehensive follow-up assessment battery (mean time to follow-up 7.5 years, range 2.4–14.9 years), which included the Childhood Trauma Questionnaire (CTQ), a self-report questionnaire that assesses experience of childhood trauma. The outcome of interest was transition to a psychotic disorder during the follow-up period. Data were available on 233 individuals. Total CTQ trauma score was not associated with transition to psychosis. Of the individual trauma types, only sexual abuse was associated with transition to psychosis (P = .02). The association remained when adjusting for potential confounding factors. Those with high sexual abuse scores were estimated to have a transition risk 2–4 times that of those with low scores. The findings suggest that sexual trauma may be an important contributing factor in development of psychosis for some individuals.Key words: trauma, psychosis, ultra high risk     

Validation of the Korean Version of the Psychosis Screener to Identify Patients With Psychosis

ObjectiveThis study aimed to validate the Korean version of a short screening tool for psychosis as the first stage in finding undiagnosed psychosis in the community. MethodsThe sample contained 126 consecutive psychiatric outpatients in National Medical Center, Seoul, Korea, between July 20 and July 22, 2020. The Psychosis Screener (PS) comprises 7 items covering psychotic symptoms. The presence of each psychotic symptom was determined by a trained mental health professional and coded “yes” or “no.” Two psychiatrists reviewed the medical records independently and extracted the ICD-10-based diagnoses. Any differences between the two clinicians were resolved by consensus, and the agreed diagnosis was used as a gold standard in the study. ResultsAmong 126 psychiatric outpatients who were enrolled in a consecutive manner during the study period, the proportion of psychosis was 15.1%. The PS showed 78.9% sensitivity and 72.0% specificity when the optimal cut-off was 2, indicating that a score of 2 or more on the screener identified a likely case of psychosis. The area under the curve for the PS was 0.78 (95% CI: 0.67–0.87). ConclusionThe Korean version of the PS has an ability to discriminate between those who meet the diagnostic criteria for psychosis and those who do not in a high-prevalence group.     

Basic Self-Disturbance Predicts Psychosis Onset in the Ultra High Risk for Psychosis “Prodromal” Population

Introduction

Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an “ultra high risk” (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder.

Methods

Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days.

Results

Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases.

Discussion

The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further “closing in” on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of “false positive” cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.     

Factors associated with psychotic symptoms in Alzheimer's disease

OBJECTIVES—Many clinical and biological factorshave been reported to be associated with the presence of psychosis inpatients with Alzheimer's disease, although the associations werevariable. The aim of this study was to clarify factors associated withthe presence of psychosis in patients with Alzheimer's disease.
METHODS—Psychiatric functioning was studied in 228 patients with Alzheimer's disease based on the results of thebehavioural pathology in Alzheimer's disease rating scale or theneuropsychiatric inventory. The effects of sex, education level, age,duration of illness, cognitive function, and apolipoprotein E genotypewere investigated for dichotomous psychotic status with a multiplelogistic regression analysis.
RESULTS—Of the 228 patients with Alzheimer'sdisease, 118 (51.8%) showed evidence of delusions or hallucinations.Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and moresevere cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was notsignificantly related to either educational level or apolipoprotein E genotype.
CONCLUSIONS—Age, sex, and severity of illness wereindependent factors associated with the presence of psychosis inpatients with Alzheimer's disease. The reason why some patients withAlzheimer's disease develop psychosis remains unclear. There may bedistinctive subtypes of Alzheimer's disease or the presence ofindividual factors which affect the development of psychosis.

     

The nucleus basalis (Ch4) in the alcoholic Wernicke-Korsakoff syndrome: reduced cell number in both amnesic and non-amnesic patients

BACKGROUND—The cholinergic nucleus basalis (Ch4)is an exclusive site of neurofibrillary degeneration in alcoholicpatients with Wernicke's encephalopathy. Aim—To testthe hypothesis that the loss of Ch4 neurons contributes to the memorydisorder, Korsakoff's psychosis, commonly seen in Wernicke's encephalopathy.
METHODS—Magnocellular basal forebrain neuronswere quantified in alcoholic patients with Wernicke's encephalopathy,both with and without Korsakoff's psychosis, and neurologicallyasymptomatic alcoholic and non-alcoholic controls. Because amnesic andnon-amnesic patients with Wernicke's encephalopathy share commonperiventricular lesions, both thiamine deficient groups as well asalcoholic patients with no neurological complications were included todetermine the lesion specific to memory impairment.
RESULTS—Ch4 cell number did not differsignificantly between alcoholic and non-alcoholic controls and therewas no correlation between cell number and lifetime alcohol intake.However, Ch4 cell number in all groups was significantly correlatedwith the volume of its major projection target, the cerebral cortex.Ch4 cell number in the non-amnesic Wernicke's encephalopathy group wassignificantly below controls (24%), with cell number in patients withKorsakoff's psychosis 21% below controls. There was considerableoverlap in cell number between groups. On discriminant analysis, therewas significantly greater cell loss in three non-amnesic patients withWernicke's encephalopathy than in some patients with Korsakoff's psychosis. The non-amnesic patient with the greatest cell loss wasimpaired on attentional tasks.
CONCLUSION—Whereas neurons in the nucleus basalisare at risk in thiamine deficient alcoholic patients, cell loss isminor and does not account for the profound memory disorder.

     

Homicide of Strangers by People with a Psychotic Illness

Background: The homicide of strangers by people with psychosis, referred to here as “stranger homicides,” are rare and tragic events that generate adverse publicity for mental health services and have resulted in significant changes in mental health policy and law. Aim: To estimate the incidence of stranger homicides, using data from previously published studies, and to compare the characteristics of psychotic offenders who killed strangers with the characteristics of those who killed a close relative. Method: Meta-analysis of the population-based studies of homicide by persons suffering from a psychosis in which the number of subjects who killed strangers was also reported. Characteristics of stranger homicide and family homicide offenders were examined in a multicenter case–control study of homicide during psychotic illness in four high-income countries. Results: A pooled estimate of 1 stranger homicide per 14.3 million people per year (95% confidence interval, 1 in 18.9 million to 1 in 11.5 million people per year) was calculated by meta-analysis of 7 studies. The characteristics of the 42 stranger homicide offenders from New South Wales [NSW], Quebec and Eastern Ontario, Finland, and the Netherlands were identified. Twenty seven (64%) of these had never previously received treatment with antipsychotic medication. The stranger homicide offenders were more likely to be homeless, have exhibited antisocial conduct, and had fewer negative symptoms than those who killed family members. The victims of stranger homicide were mostly adult males and the homicides rarely occurred in the victim’s home or workplace. Conclusions: Stranger homicide in psychosis is extremely rare and is even rarer for a patient who has received treatment with antipsychotic medication. A lack of distinguishing characteristics of stranger homicide offenders and an extremely low base rate of stranger-homicide suggests that risk assessment of patients known to have a psychotic illness will be of little assistance in the prevention of stranger homicides.     

Preliminary evidence for a relationship between prospective memory and PTSD symptoms in the general population

IntroductionPTSD sufferers often have problems with remembering the past, but do they also have trouble remembering tasks to be completed in the future? We argue characteristics of PTSD—such as negative appraisals and maladaptive strategies—might contribute to biased reporting of prospective memory failures among PTSD sufferers—or people with severe PTSD symptoms—within a general population.MethodsMechanical Turk participants completed a questionnaire battery measuring self-report prospective memory, PTSD symptoms, negative appraisals and maladaptive strategies (e.g., suppression), and depression, anxiety and stress symptoms.ResultsPTSD symptom severity positively correlated with self-report prospective memory failures (rs = .42–49). PTSD symptoms affected self-report prospective memory via their influence on negative appraisals and maladaptive strategies.LimitationsOur findings rely on self-report, therefore we do not know if this relationship generalizes to objective prospective memory tasks.ConclusionsOur data provide preliminary evidence for a relationship between PTSD symptomatology and subjective prospective memory in the general population and suggest that the negative appraisals and maladaptive strategies that commonly accompany PTSD might underpin this relationship.     

Timing,Distribution, and Relationship Between Nonpsychotic and Subthreshold Psychotic Symptoms Prior to Emergence of a First Episode of Psychosis

Prospective population studies suggest that psychotic syndromes may be an emergent phenomenon—a function of severity and complexity of more common mental health presentations and their nonpsychotic symptoms. Examining the relationship between nonpsychotic and subthreshold psychotic symptoms in individuals who later developed the ultimate outcome of interest, a first episode of psychosis (FEP), could provide valuable data to support or refute this conceptualization of how psychosis develops. We therefore conducted a detailed follow-back study consisting of semistructured interviews with 430 patients and families supplemented by chart reviews in a catchment-based sample of affective and nonaffective FEP. The onset and sequence of 27 pre-onset nonpsychotic (NPS) or subthreshold psychotic (STPS) symptoms was systematically characterized. Differences in proportions were analyzed with z-tests, and correlations were assessed with negative binomial regressions. Both the first psychiatric symptom (86.24% NPS) and the first prodromal symptom (66.51% NPS) were more likely to be NPS than STPS. Patients reporting pre-onset STPS had proportionally more of each NPS than did those without pre-onset STPS. Finally, there was a strong positive correlation between NPS counts (reflecting complexity) and STPS counts (β = 0.34, 95% CI [0.31, 0.38], P < 2 e-16). Prior to a FEP, NPS precede STPS, and greater complexity of NPS is associated with the presence and frequency of STPS. These findings complement recent arguments that the emergence of psychotic illness is better conceptualized as part of a continuum—with implications for understanding pluripotential developmental trajectories and strengthening early intervention paradigms.     

Jumping to Conclusions,Neuropsychological Functioning,and Delusional Beliefs in First Episode Psychosis

Background: The “jumping to conclusions” (JTC) data-gathering bias is implicated in the development and maintenance of psychosis but has only recently been studied in first episode psychosis (FEP). In this study, we set out to establish the relationship of JTC in FEP with delusions and neuropsychological functioning. Methods: One hundred and eight FEP patients and 101 age-matched controls completed assessments of delusions, general intelligence (IQ), working memory (WM), and JTC (the probabilistic reasoning “beads” task). Results: Half the FEP participants jumped to conclusions on at least 1 task, compared with 25% of controls (OR range 2.1 to 3.9; 95% CI range 1.5 to 8.0, P values ≤ .02). JTC was associated with clinical, but not nonclinical delusion severity, and with neuropsychological functioning, irrespective of clinical status. Both IQ and delusion severity, but not WM, were independently associated with JTC in the FEP group. Conclusions: JTC is present in FEP. The specific association of JTC with clinical delusions supports a state, maintaining role for the bias. The associations of JTC with neuropsychological functioning indicate a separable, trait aspect to the bias, which may confer vulnerability to psychosis. The work has potential to inform emerging interventions targeting reasoning biases in early psychosis.Key words: psychosis, delusions, reasoning, jumping to conclusions, neuropsychology     

Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: “Poor,” “Middle,” “Catch-up,” and “Good” trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F_3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the “Poor” outcome cluster (β = +0.145) but decreased over time in the “Catch-up” cluster (β = −0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery.     

Comorbid Depressive and Anxiety Disorders in 509 Individuals With an At-Risk Mental State: Impact on Psychopathology and Transition to Psychosis

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients.Key words: psychosis, schizophrenia, ultra high risk, ARMS, prodromal, attenuated psychosis, psychosis risk, depression, anxiety