Shelly Ben-David

Obsessive compulsive symptoms in individuals at clinical risk for psychosis: Association with depressive symptoms and suicidal ideation

Obsessive-compulsive symptoms, particularly aggressive obsessions, are prevalent in schizophrenia patients and associated with other symptom severity, suicidal ideation and functional impairment. In a psychosis-risk cohort, obsessive-compulsive diagnosis and symptoms were assessed in terms of prevalence and content, and for associations with clinical measures. Obsessive-compulsive symptoms were prevalent in the CHR cohort, as was suicidal ideation. The presence and severity of aggressive obsessions were associated with depression, suicidal ideation and social impairment. The high prevalence of aggressive obsessions and associated suicidal ideation in a clinical high risk cohort, and their relationship to depression, is relevant for risk assessment and treatment strategies.

Auditory event-related potentials and alpha oscillations in the psychosis prodrome: Neuronal generator patterns during a novelty oddball task

Prior research suggests that event-related potentials (ERP) obtained during active and passive auditory paradigms, which have demonstrated abnormal neurocognitive function in schizophrenia, may provide helpful tools in predicting transition to psychosis. In addition to ERP measures, reduced modulations of EEG alpha, reflecting top-down control required to inhibit irrelevant information, have revealed attentional deficits in schizophrenia and its prodromal stage. Employing a three-stimulus novelty oddball task, nose-referenced 48-channel ERPs were recorded from 22 clinical high-risk (CHR) patients and 20 healthy controls detecting target tones (12% probability, 500Hz; button press) among nontargets (76%, 350Hz) and novel sounds (12%). After current source density (CSD) transformation of EEG epochs (-200 to 1000ms), event-related spectral perturbations were obtained for each site up to 30Hz and 800ms after stimulus onset, and simplified by unrestricted time-frequency (TF) principal components analysis (PCA). Alpha event-related desynchronization (ERD) as measured by TF factor 610-9 (spectral peak latency at 610ms and 9Hz; 31.9% variance) was prominent over right posterior regions for targets, and markedly reduced in CHR patients compared to controls, particularly in three patients who later developed psychosis. In contrast, low-frequency event-related synchronization (ERS) distinctly linked to novels (260-1; 16.0%; mid-frontal) and N1 sink across conditions (130-1; 3.4%; centro-temporoparietal) did not differ between groups. Analogous time-domain CSD-ERP measures (temporal PCA), consisting of N1 sink, novelty mismatch negativity (MMN), novelty vertex source, novelty P3, P3b, and frontal response negativity, were robust and closely comparable between groups. Novelty MMN at FCz was, however, absent in the three converters. In agreement with prior findings, alpha ERD and MMN may hold particular promise for predicting transition to psychosis among CHR patients.

Attributional Style among Youth at Clinical Risk for Psychosis

Aim: A biased attributional style, in which negative events are attributed to external and personal causes, is associated with paranoid delusions in schizophrenia. It is not known whether this biased attributional style also characterizes individuals at clinical risk for psychosis or if it is associated with their emergent paranoia.

Symptom trajectories and psychosis onset in a clinical high-risk cohort: The relevance of subthreshold thought disorder

BACKGROUND Prior studies have implicated baseline positive and negative symptoms as predictors of psychosis onset among individuals at clinical high risk (CHR), but none have evaluated latent trajectories of symptoms over time. This study evaluated the dynamic evolution of symptoms leading to psychosis onset in a CHR cohort. METHOD 100 CHR participants were assessed quarterly for up to 2.5 years. Latent trajectory analysis was used to identify patterns of symptom change. Logistic and proportional hazards models were employed to evaluate the predictive value for psychosis onset of baseline symptoms and symptom trajectories. RESULTS Transition rate to psychosis was 26%. Disorganized communication (i.e., subthreshold thought disorder) presented an increased hazard for psychosis onset, both at baseline (Hazard Ratio (95% CI)=1.4 (1.1-1.9)) and as a trajectory of high persistent disorganized communication (Hazard Ratio (95% CI)=2.2 (1.0-4.9)). Interval clinical data did not improve the predictive value of baseline symptoms for psychosis onset. CONCLUSIONS High baseline disorganized communication evident at ascertainment tended to persist and lead to psychosis onset, consistent with prior behavioral and speech analysis studies in similar cohorts. Remediation of language dysfunction therefore may be a candidate strategy for preventive intervention.

Reasons for cannabis use among youths at ultra high risk for psychosis

Cannabis use is prevalent in schizophrenia and its risk states, despite its association with anxiety and positive symptoms. While schizophrenia patients report using cannabis for mood enhancement and social motives, it is not known what motivates clinical high risk (CHR) patients to use cannabis.

Cognitive insight in individuals at clinical high risk for psychosis

Reduced cognitive insight has been associated with psychotic symptoms, in particular with the presence of delusions; however, there is little information about whether such reductions are present in at‐risk individuals prior to the onset of threshold psychotic symptoms.

Smell identification in individuals at clinical high risk for schizophrenia

Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders.

Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity

Background/Objectives:Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing.Methods:In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustment Self-Report Scale), social and physical anhedonia (Chapman Revised Anhedonia Scales), and social anxiety (Social Anxiety Scale for Adolescents) in cross-section. In a subgroup of 25 CHR individuals for whom high-spatial-resolution basal-state functional magnetic resonance imaging data were available, we also assessed correlations of these socio-affective constructs with basal cerebral blood volume in orbitofrontal cortex and related regions involved in reward processing.Results:Relative to controls, CHR individuals reported social impairment, greater social and physical anhedonia, and more social anxiety, exhibiting impairments comparable to schizophrenia. Regression analyses showed that anhedonia predicted social impairment and correlated negatively with basal cerebral blood volume within the orbitofrontal cortex (all P’s<0.05).Conclusions:Anhedonia and social anxiety are prominent in CHR individuals. Trait-like anhedonia may be a core phenotype related to orbitofrontal cortical function that, independent of symptoms, predicts social impairment. These data provide a rationale for interventions that target anhedonia and related activity in orbitofrontal cortical circuits in CHR individuals.

Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort

BACKGROUND DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

Social inference in individuals at clinical high risk for psychosis

Social cognition impairment is a hallmark of schizophrenia and contains multiple domains. The domain of social inference has been relatively understudied in schizophrenia and its risk states.