Dorien H. Nieman

Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis.

BACKGROUND The chance of transition to psychosis in patients at Ultra High Risk for developing psychosis (UHR) is 10-15%. The aim of present study was to investigate differences in baseline clinical symptomatology, general level of functioning (GAF-score) and genetic risk between UHR patients who did (UHR+T) or did not (UHR+NT) make a transition to psychosis. Sharpening UHR inclusion criteria may aid in improving prediction of transition to psychosis. METHOD The study sample was taken from 285 patients who were examined within the Dutch Prediction of Psychosis Study (DUPS) at the Academic Medical Center of the University of Amsterdam, the Netherlands. Out of 73 included UHR subjects, 18 made a transition to psychosis. Psychopathology was investigated with the Structured Interview for Prodromal Syndromes, Bonn Scale for the Assessment of Basic Symptoms and GAF-score. The follow-up period of the study was three years. RESULTS The UHR+T group showed more social anhedonia and withdrawal, more bizarre thinking and a lower GAF score at baseline than the UHR+NT group. CONCLUSIONS In agreement with the results of Cannon et al. [Cannon, T.D., Cadenhead, K., Cornblatt, B., Woods, S.W., Addington, J., Walker, E., Seidman, L.J., Perkins, D., Tsuang, M., McGlashan, T., Heinssen, R., 2008. Prediction of Psychosis in Youth at High Clinical Risk: A Multisite Longitudinal Study in North America. Arch. Gen. Psychiat. 65 (1) 28-37.], our study indicates that severity of specific symptoms at baseline is related to transition to psychosis in UHR subjects. These findings may contribute to a more accurate prediction of a first psychotic episode. Furthermore, symptoms that are increased at baseline in the UHR+T group could be a focus of cognitive behavioural therapy in the UHR period.

Ultra high-risk state for psychosis and non-transition: a systematic review

BACKGROUND Most effort in ultra high-risk (UHR) research has been directed at defining the clinical and neurobiological characteristics of those UHR subjects who go on to develop psychosis. The characteristics and outcome of the remaining UHR subjects have remained relatively unexplored. METHOD We performed a systematic review of clinical UHR studies to investigate whether information was available on the characteristics and outcome of UHR subjects who did not convert to psychosis. RESULTS Of 2462 potentially relevant papers, 31 met inclusion criteria, i.e. 20 naturalistic and 11 intervention studies. On average 76% (range 46-92.6%) of the UHR patients made no transition to psychosis during follow-up (range 6 to 40 months). Nearly half of the studies provided no characteristics of those UHR subjects who did not develop psychosis. Six studies reported remission rates from initial UHR status (range 15.4% to 54.3%). Linear regression showed that more recent studies reported significantly lower transition rates as compared to earlier publications. An older mean age at baseline was associated with significant lower transition rates in publications with follow-ups exceeding 1 year. CONCLUSIONS Our review illustrates that the long-term outcome of UHR subjects that do not develop psychosis is to date under-investigated. The studies reporting remission rates suggest that UHR criteria capture a non-negligible proportion of subjects that do not convert to psychosis.

Cognitive Behavioral Therapy for Subjects at Ultrahigh Risk for Developing Psychosis: A Randomized Controlled Clinical Trial

BACKGROUND Evidence for the effectiveness of treatments for subjects at ultrahigh risk (UHR) for developing psychosis remains inconclusive. OBJECTIVE A new cognitive behavioral intervention specifically targeted at cognitive biases (ie, Cognitive Behavioral Therapy [CBT] for UHR patients plus treatment as usual [TAU] called CBTuhr) is compared with TAU in a group of young help-seeking UHR subjects. METHODS A total of 201 patients were recruited at 4 sites and randomized. In most cases, CBTuhr was an add-on therapy because most people were seeking help for a comorbid disorder. The CBT was provided for 6 months, and the follow-up period was 18 months. RESULTS In the CBTuhr condition, 10 patients transitioned to psychosis compared with 22 in the TAU condition (χ(2) (1) = 5.575, P = .03). The number needed to treat (NNT) was 9 (95% confidence interval [CI]: 4.7-89.9). At 18-month follow-up the CBTuhr group was significantly more often remitted from an at-risk mental state, with a NNT of 7 (95% CI: 3.7-71.2). Intention-to-treat analysis, including 5 violations against exclusion criteria, showed a statistical tendency (χ(2) (1) = 3.338, P = .06). CONCLUSIONS Compared with TAU, this new CBT (focusing on normalization and awareness of cognitive biases) showed a favorable effect on the transition to psychosis and reduction of subclinical psychotic symptoms in subjects at UHR to develop psychosis.

Disability in people clinically at high risk of psychosis

BACKGROUND Decline in social functioning occurs in individuals who later develop psychosis. AIMS To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

IMPORTANCE Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

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.

Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis

Dragt S, Nieman DH, Schultze‐Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RKR, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH, on behalf of the EPOS group. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis.

Environmental factors and social adjustment as predictors of a first psychosis in subjects at ultra high risk

BACKGROUND The onset of schizophrenia is associated with genetic, symptomatic, social and environmental risk factors. The aim of the present study was to determine which environmental factors may contribute to a prediction of a first psychotic episode in subjects at Ultra High Risk (UHR) for developing psychosis. METHOD We included 72 UHR subjects and followed them over a period of 36 months, of whom nineteen (26.4%) made a transition to psychosis. We applied survival analyses to determine associations between a transition to psychosis and environmental factors and social adjustment. To determine which items are the best predictors of transition to a first psychotic episode, Cox Regression analyses were applied. RESULTS Urbanicity, receiving state benefits and poor premorbid adjustment (PMA) significantly influenced the transition to psychosis. Urbanicity (Wald=10.096, p=.001, HR=30.97), social-sexual aspects (Wald=8.795, p=.003, HR=1.91) and social-personal adjustment (Wald=10.794, p=.001, HR=4.26) appeared to be predictors for developing psychosis in our UHR group. CONCLUSIONS Environmental characteristics and social adjustment are predictive of transition to a psychosis in subjects at UHR. These characteristics should be implemented in a model for prediction of psychosis. Such a model would be more specific than current models and may lead to patient-specific preventive interventions.

Neuropsychological and clinical correlates of antisaccade task performance in schizophrenia.

Objectives: To elucidate pathophysiologic mechanisms involved in abnormal antisaccade task performance in schizophrenia by investigating a possible relationship among antisaccade task performance, neuropsychological test results, and symptomatology in a group of young patients with recent-onset schizophrenia; to compare the effects of olanzapine and risperidone on antisaccades and reflexive saccades. Background: Patients with schizophrenia consistently perform worse than controls on the antisaccade task in which the subject is required to inhibit a reflexive saccade to a suddenly appearing visual target and look in the opposite direction. Methods: In 37 young (mean age 21 years), medicated patients with recent-onset schizophrenia the authors assessed antisaccades, reflexive saccades, neuropsychological test performance, and symptomatology. A subgroup of 18 patients was treated with olanzapine, and 15 patients were treated with risperidone. Reflexive-saccade and antisaccade task results were compared with those obtained in 13 control subjects. Results: The antisaccade error rate was significantly higher in the patients than in the control subjects. In the patients, poor working memory function was related to increased antisaccade error rate. Severity of disorganization symptoms at intake was related to prolonged mean latency of the correct antisaccades. Patients on risperidone had a prolonged mean latency in the reflexive saccade task compared with patients using olanzapine. Conclusions: Abnormal antisaccade task performance is already present in early schizophrenia and may reflect working memory dysfunction. In future studies, medication effects should be considered in interpreting eye movement test results of patients with schizophrenia.

Detection of people at risk of developing a first psychosis: comparison of two recruitment strategies

Rietdijk J, Klaassen R, Ising H, Dragt S, Nieman DH, van de Kamp J, Cuijpers P, Linszen D, van der Gaag M. Detection of people at risk of developing a first psychosis: comparison of two recruitment strategies.