Rachel Loewy

Neurocognitive performance and functional disability in the psychosis prodrome

OBJECTIVE This study evaluates the pattern of neuropsychological deficits and their association with clinical symptomatology and social functioning in individuals identified as ultra-high-risk (UHR) for psychosis. METHODS A sample of 45 UHR individuals was identified using the Structured Interview for Prodromal Syndromes (SIPS) from consecutive referrals to the Staglin Music Festival Center for the Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants were administered a neurocognitive test battery, as well as measures of global (Strauss-Carpenter Outcome Scale) and social functioning (UCLA Social Attainment Survey). RESULTS Participants showed significant deficits in speed of processing, verbal learning and memory, and motor speed. Poorer verbal learning and memory performance was significantly associated with poorer social functioning, and there was a trend for poorer performance on reasoning and problem solving to be associated with poorer global functioning. Verbal memory independently predicted social functioning over and above severity of negative symptoms. Cognitive deficits were not associated with severity of clinical symptomatology. CONCLUSIONS Despite the absence of fully psychotic symptoms, UHR individuals experience significant cognitive deficits, particularly on tasks requiring speeded information-processing and efficient recall from memory, and these deficits appear to be associated with functional disability in a manner parallel to that observed in patients with established psychotic illness.

The prodromal questionnaire (PQ): Preliminary validation of a self-report screening measure for prodromal and psychotic syndromes

This study aims to establish preliminary validity of the Prodromal Questionnaire (PQ), a 92-item self-report screening measure for prodromal and psychotic symptoms. Adolescents and young adults (N = 113) referred to a prodromal psychosis research clinic completed the PQ and the Structured Interview for Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an interview with established validity for predicting future psychosis. When maximizing selection of true positive cases, scores on a subset of PQ items that assess positive symptoms predicted a concurrent prodromal or psychotic SIPS diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary validity in detecting individuals with an interview-diagnosed prodromal or psychotic syndrome, but it is less sensitive to the threshold between prodromal and full-blown psychosis.

Psychosis risk screening with the Prodromal Questionnaire--brief version (PQ-B).

In this study, we examined the preliminary concurrent validity of a brief version of the Prodromal Questionnaire (PQ-B), a self-report screening measure for psychosis risk syndromes. Adolescents and young adults (N=141) who presented consecutively for clinical assessment to one of two early psychosis research clinics at the University of California, San Francisco and UC Los Angeles completed the PQ-B and the Structured Interview for Prodromal Syndromes (SIPS) at intake. Endorsement of three or more positive symptoms on the PQ-B differentiated between those with prodromal syndrome and psychotic syndrome diagnoses on the SIPS versus those with no SIPS diagnoses with 89% sensitivity, 58% specificity, and a positive Likelihood Ratio of 2.12. A Distress Score measuring the distress or impairment associated with endorsed positive symptoms increased the specificity to 68%, while retaining similar sensitivity of 88%. Agreement was very similar when participants with psychotic syndromes were excluded from the analyses. These results suggest that the PQ-B may be used as an effective, efficient self-report screen for prodromal psychosis syndromes when followed by diagnostic interview, in a two-stage evaluation process in help-seeking populations.

The Validity of the 16-Item Version of the Prodromal Questionnaire (PQ-16) to Screen for Ultra High Risk of Developing Psychosis in the General Help-Seeking Population

In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were help-seeking for nonpsychotic disorders at the secondary mental health services in The Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.

Neuroplasticity-Based Auditory Training Via Laptop Computer Improves Cognition in Young Individuals With Recent Onset Schizophrenia

OBJECTIVE Cognitive deficits that characterize schizophrenia are present in the prodrome, worsen with illness onset, and predict functional outcome. Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia. METHOD This 2-site double-blind randomized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks. We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and functioning. We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement. RESULTS Auditory training subjects demonstrated significant improvements in global cognition, verbal memory, and problem solving compared with those of computer games control subjects. Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures. Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours. CONCLUSION Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia. An individuals baseline motivational system functioning (reward anticipation), and ability to engage in auditory processing speed improvement, may represent important predictors of treatment outcome. Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions.

Motor dysfunction and risk for schizophrenia.

Motor dysfunction is associated with schizophrenia, and recent longitudinal studies indicate that it precedes the onset of clinical symptoms. Of particular interest is the heightened occurrence of involuntary movements, which are apparent as early as infancy and suggest the presence of subcortical brain abnormalities. In this article, we present the results of a study of spontaneous movements in adolescents with schizotypal personality disorder (SPD). SPD is a syndrome that has been shown to be genetically linked with schizophrenia and is often observed prior to the early adult onset of schizophrenia. Systematic coding of videotapes of diagnostic interviews revealed that the SPD group showed significantly more involuntary movements of the head, trunk, and upper limbs than did normals and adolescents with other personality disorders. There were no diagnostic group differences in the rate of voluntary movements. Salivary cortisol, measured before the interview, was positively correlated with involuntary movements. Taken together, the findings provide further support for the hypothesized etiologic relation between SPD and schizophrenia. Based on a neural diathesis-stress model, potential underlying mechanisms are discussed.

Cognitive Interventions Targeting Brain Plasticity in the Prodromal and Early Phases of Schizophrenia

Several important paradigm shifts have occurred in the field of schizophrenia treatment, including an increased focus on early detection, the development of preemptive interventions, and the view of schizophrenia as a neurodevelopmental disease characterized by decreased efficiency and abnormal connectivity in cortical and subcortical neural networks. In this review, we briefly describe some of the neural impairments that contribute to the development of schizophrenia, with an emphasis on the impact of stress and trauma on cognitively vulnerable neural systems. We then present current data on two behavioral interventions that target these critical risk factors and that aim to preempt the onset of schizophrenia in vulnerable individuals or improve the clinical course in recent-onset schizophrenia: cognitive therapy and computerized cognitive training.

Prodromal psychosis screening in adolescent psychiatry clinics

Background: Research has identified a syndrome conferring ultra‐high risk (UHR) for psychosis, although UHR interviews require intensive staff training, time and patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to screen more efficiently for UHR syndromes.

Motivational deficits in individuals at-risk for psychosis and across the course of schizophrenia

Motivational impairment is a critical factor that contributes to functional disability in schizophrenia and undermines an individuals ability to engage in and adhere to effective treatment. However, little is known about the developmental trajectory of deficits in motivation and whether these deficits are present prior to the onset of psychosis. We assessed several components of motivation including anticipatory versus consummatory pleasure (using the Temporal Experience of Pleasure Scale (TEPS)), and behavioral drive, behavioral inhibition, and reward responsivity (using the Behavioral Inhibition Scale/Behavioral Activation Scale (BIS/BAS)). A total of 234 participants completed study measures, including 60 clinical high risk (CHR) participants, 60 recent-onset schizophrenia participants (RO), 78 chronic schizophrenia participants (SZ) and 29 healthy controls (HC) age matched to the CHR group. CHR participants endorsed greater deficits in anticipatory pleasure and reward responsivity, relative to HC comparison participants and individuals diagnosed with schizophrenia. Motivational deficits were not more pronounced over the course of illness. Depressed mood was uniquely associated with impairments in motivation in the CHR sample, but not the schizophrenia participants. The results suggest that CHR individuals experience multiple contributors to impaired motivation, and thus multiple leverage points for treatment.

Predicting the longitudinal effects of the family environment on prodromal symptoms and functioning in patients at-risk for psychosis

The current study examined the relationship between the family environment and symptoms and functioning over time in a group of adolescents and young adults at clinical high risk for psychosis (N=63). The current study compared the ability of interview-based versus self-report ratings of the family environment to predict the severity of prodromal symptoms and functioning over time. The family environmental factors were measured by interviewer ratings of the Camberwell Family Interview (CFI), self-report questionnaires surveying the patients perceptions of criticism and warmth, and parent reported perceptions of their own level of criticism and warmth. Patients living in a critical family environment, as measured by the CFI at baseline, exhibited significantly worse positive symptoms at a 6-month follow-up, relative to patients living in a low-key family environment. In terms of protective effects, warmth and an optimal level of family involvement interacted such that the two jointly predicted improved functioning at the 6-month follow-up. Overall, both interview-based and self-report ratings of the family environment were predictive of symptoms and functioning at follow-up; however patients self-report ratings of criticism had stronger predictive power. These results suggest that the family environment should be a specific target of treatment for individuals at risk for psychosis.