Daniela Spiliotacopoulos

Long-term Follow-up of a Group at Ultra High Risk (“Prodromal”) for Psychosis: The PACE 400 Study

IMPORTANCE The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known. OBJECTIVE To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry. DESIGN Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006. SETTING The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia. PARTICIPANTS Four hundred sixteen UHR patients previously seen at the PACE clinic. MAIN OUTCOMES AND MEASURES Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records. RESULTS During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content. CONCLUSIONS AND RELEVANCE The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high risk for psychosis

BACKGROUND AND AIM Little is known about the relationship between neurocognitive performance and functional outcome before the onset of frank psychosis. This longitudinal study aimed to investigate neurocognitive predictors of poor functional outcome in a group identified as ultra-high risk (UHR) for psychosis between two and 13 years prior. METHOD Individuals (N=230) identified as UHR for psychosis at the PACE Clinic in Melbourne completed assessment of psychopathology, functioning and neurocognition at baseline and follow-up. The mean length of follow-up was 7.26 years (SD 3.05). RESULTS Forty-one individuals with the poorest functional outcome were identified. Only 48.8% of this group had transitioned to psychosis. Poor functional outcome was associated with reduced performance at baseline in the specific neurocognitive domains of verbal learning and memory, processing speed and attention, and verbal fluency, but not global cognitive impairment. Reduced performance on a verbal story recall task, in combination with higher negative symptoms at baseline, was the best predictor of later poor outcome. Baseline positive psychotic symptoms and GAF scores were not associated with later poor outcome. DISCUSSION To date, this is the longest follow-up study of an UHR sample. Poor functional outcome was associated with specific neurocognitive decrements, regardless of transition to psychosis. The detection of individuals with poor functioning at follow-up, against a background of previously identified risk factors for psychotic disorder, may yield a valid group in which to study biomarkers and treatment of schizophrenia.

Family Outcomes From a Randomized Control Trial of Relapse Prevention Therapy in First-Episode Psychosis

OBJECTIVE We have previously reported that our combined individual and family cognitive-behavioral therapy (CBT) relapse prevention therapy (RPT) was effective in reducing relapse rates compared to treatment as usual (TAU) within a specialist program for young, first-episode psychosis patients who had reached remission on positive symptoms. Here, we report the outcomes for family participants of DSM-IV-diagnosed first-episode psychosis patients recruited between November 2003 and May 2005 over a 2.5-year follow-up period. The primary hypothesis was that, compared to family members receiving TAU, family participants who received RPT would have significantly improved appraisals of stressors related to caregiving. Secondary hypotheses were that RPT would be associated with reduced expressed emotion and improved psychological distress. METHOD Family members were assessed at baseline and at 7-month, 12-month, 18-month, 24-month, and 30-month follow-up on appraisal of caregiving, expressed emotion, and psychological distress using the Experience of Caregiving Inventory, The Family Questionnaire, and the General Health Questionnaire of 28 Items, respectively. The family component of RPT was based on family behavioral therapy for schizophrenia with a specific focus on psychoeducation and CBT for relapse prevention. RESULTS Thirty-two families received RPT, and 31 families received TAU. There were significant group effects for aspects of the appraisal of caregiving, including negative symptoms, positive personal experiences, and total positive score on the Experience of Caregiving Inventory. Time effects were evident for emotional overinvolvement and for aspects of the appraisal of caregiving. There were no significant effects for psychological distress. CONCLUSIONS The relatives of patients who received RPT perceived less stress related to their relatives negative symptoms and an increase in perceived opportunities to make a positive contribution to the care of their relative compared to carers in the TAU condition. Cognitive-behavioral therapy for relapse prevention showed promise in improving the experience of caregiving for family members of first-episode psychosis patients over a 2.5-year follow-up period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000514606.

Predictors of Adherence to Cognitive-Behavioural Therapy in First-Episode Psychosis:

Objective: To investigate predictors of adherence with a cognitive-behavioural intervention in first-episode psychosis (FEP) patients. Method: Predictors of adherence to cognitive-behavioural therapy (CBT) were longitudinally investigated in the experimental arm of a randomized controlled trial designed to evaluate the effectiveness of a CBT intervention for relapse prevention early in the course of psychosis when compared with treatment as usual within 2 high quality, youth oriented, specialist FEP programs (the EPISODE II trial). Results: Longer duration of untreated psychosis (DUP) and poorer level of insight predicted poor adherence to CBT. This association remained significant after controlling for potential confounders. Conclusions: Treatment delay may decrease adherence with CBT in FEP patients. Reducing DUP and promoting insight early in the course of psychosis are likely to enhance adherence with CBT.

A Randomized Controlled Trial of Relapse Prevention Therapy for First-Episode Psychosis Patients: Outcome at 30-Month Follow-Up

The effectiveness of a novel 7-month psychosocial treatment designed to prevent the second episode of psychosis was evaluated in a randomized controlled trial at 2 specialist first-episode psychosis (FEP) programs. An individual and family cognitive behavior therapy for relapse prevention was compared with specialist FEP care. Forty-one FEP patients were randomized to the relapse prevention therapy (RPT) and 40 to specialist FEP care. Participants were assessed on an array of measures at baseline, 7- (end of therapy), 12-, 18-, 24-, and 30-month follow-up. At 12-month follow-up, the relapse rate was significantly lower in the therapy condition compared with specialized treatment alone (P = .039), and time to relapse was significantly delayed for those in the relapse therapy condition (P = .038); however, such differences were not maintained. Unexpectedly, psychosocial functioning deteriorated over time in the experimental but not in the control group; these differences were no longer statistically significant when between-group differences in medication adherence were included in the model. Further research is required to ascertain if the initial treatment effect of the RPT can be sustained. Further research is needed to investigate if medication adherence contributes to negative outcomes in functioning in FEP patients who have reached remission, or, alternatively, if a component of RPT is detrimental.

Demographic and clinical characteristics of young people seeking help at youth mental health services: baseline findings of the Transitions Study.

The Transitions Study was designed to establish a cohort of young people (12–25 years) seeking help for mental health problems, in order to longitudinally explore and refine a clinical staging model of the development and progression of mental disorders. This paper presents the baseline demographic and clinical characteristics of the cohort, particularly the nature and severity of psychopathology.

Transitions Study of predictors of illness progression in young people with mental ill health: study methodology

An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13–24‐year‐olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post‐pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder.

Longitudinal Cognitive Performance in Individuals at Ultrahigh Risk for Psychosis: A 10-year Follow-up

It remains unclear whether the onset of psychosis is associated with deterioration in cognitive performance. The aim of this study was to examine the course of cognitive performance in an ultrahigh risk (UHR) cohort, and whether change in cognition is associated with transition to psychosis and change in functioning. Consecutive admissions to Personal Assessment and Crisis Evaluation (PACE) Clinic between May 1994 and July 2000 who had completed a comprehensive cognitive assessment at baseline and follow-up were eligible (N = 80). Follow-up ranged from 7.3 to 13.4 years (M = 10.4 years; SD = 1.5). In the whole sample, significant improvements were observed on the Similarities (P = .03), Information (P < .01), Digit Symbol Coding (P < .01), and Trail Making Test-B (P = .01) tasks, whereas performance on the Rey Auditory Verbal Learning Test (Trials 1-3) declined significantly (P < .01) over the follow-up period. Change in performance on cognitive measures was not significantly associated with transition status. Taking time to transition into account, those who transitioned after 1 year showed significant decline on Digit Symbol Coding, whereas those who did not transition improved on this measure (P = .01; effect size [ES] = 0.85). Small positive correlations were observed between improvements in functioning and improvements in performance on Digit Symbol Coding and Arithmetic (0.24, P = .03 and 0.28, P = .01, respectively). In summary, the onset of psychosis was not associated with deterioration in cognitive ability. However, specific findings suggest that immediate verbal learning and memory, and processing speed may be relevant domains for future risk models and early intervention research in UHR individuals.