Kelly E. Gill

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.

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.

The impact of emotion awareness and regulation on social functioning in individuals at clinical high risk for psychosis.

BACKGROUND Social functioning (SF) difficulties are ubiquitous among individuals at clinical high risk for psychosis (CHR), but it is not yet clear why. One possibility is suggested by the observation that effective SF requires adaptive emotion awareness and regulation. Previous reports have documented deficits in emotion awareness and regulation in individuals with schizophrenia, and have shown that such deficits predicted SF. However, it is unknown whether these deficits are present prior to the onset of psychosis or whether they are linked to SF in CHR individuals. METHOD We conducted a cross-sectional comparison of emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia and 50 healthy controls (HC). Then, within the CHR group, we examined links between emotion awareness, emotion regulation and SF as indexed by the Global Functioning Scale: Social (Cornblatt et al. 2007). RESULTS Group comparisons indicated significant differences between HC and the two clinical groups in their ability to identify and describe feelings, as well as the use of suppression and reappraisal emotion-regulation strategies. Specifically, the CHR and schizophrenia groups displayed comparable deficits in all domains of emotion awareness and emotion regulation. A hierarchical multiple regression analysis indicated that difficulties describing feelings accounted for 23.2% of the SF variance. CONCLUSIONS The results indicate that CHR individuals display substantial emotion awareness and emotion-regulation deficits, at severity comparable with those observed in individuals with schizophrenia. Such deficits, in particular difficulties describing feelings, predate the onset of psychosis and contribute significantly to poor SF in this population.

Assessing suicidal ideation in individuals at clinical high risk for psychosis

BACKGROUND The majority of individuals with schizophrenia and other psychotic illnesses have had suicidal ideation at some point during the illness. However, little is known about the variation in level and intensity of suicidal ideation and symptoms in the attenuated stage of psychotic illness. Our aims were to assess prevalence of suicidal ideation in this at risk group, and to examine the severity and intensity of suicidal ideation, and their relation to symptoms. METHODS Suicidal ideation was assessed in 42 clinical high-risk participants using the Columbia Suicide Severity Rating Scale (C-SSRS). We hypothesized that prevalence rates would be similar to what was found in previous studies, and individuals with suicidal ideation would have higher positive and negative symptoms, with poorer functioning. We assessed levels of severity and intensity of suicidal ideation related to these symptoms, and examined how depressive symptoms affected these relationships. RESULTS Nearly half (42.9%) of participants reported having current suicidal ideation. We found no relationship to positive symptoms. However, severity and intensity of suicidal ideation were found to be related to negative symptoms and level of functioning. When controlling for depressive symptoms during exploratory analysis, this relationship still emerged. CONCLUSIONS This study adds to the literature demonstrating the complex nature of suicidal ideation in psychotic illness. The C-SSRS has shown to be helpful in determining relationships between severity and intensity in suicidal ideation in relation to specific symptoms in a research setting.

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.

Various neurocognitive deficits and conversion risk in individuals at clinical high risk for psychosis

Individuals at clinical high risk for psychosis (CHR) exhibit neurocognitive deficits in multiple domains. The aim of this study is to investigate whether several components of neurocognition are predictive of conversion to psychosis.

Sleep disturbances in individuals at clinical high risk for psychosis

There has been recent interest in understanding the role that sleep disturbance plays in patients at Clinical High Risk for psychosis (CHR). We assessed sleep disturbance in 194 CHR patients and 66 healthy control subjects and their relationship to symptoms (positive, negative and general functioning). Patients experienced significantly more sleep disturbance than healthy control subjects and their sleep disturbance was related to greater positive and negative symptoms and worse overall functioning. Targeting sleep disturbance in CHR individuals may provide alternative means of treating the CHR syndrome.

Neural Dysfunction in Cognitive Control Circuits in Persons at Clinical High-Risk for Psychosis

Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared with controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR non-converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and with functional outcome.