Helga K. Ising

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.

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.

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.

A single blind randomized controlled trial of cognitive behavioural therapy in a help-seeking population with an At Risk Mental State for psychosis: the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial

BackgroundPsychotic disorders are a serious mental health problem. Intervention before the onset of psychosis might result in delaying the onset, reducing the impact or even preventing the first episode of psychosis. This study explores the effectiveness of cognitive behavioural therapy (CBT) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra-high risk for developing psychosis. A single blind randomised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis.Method/designAll help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherlands are pre-screened with the Prodromal Questionnaire during a period of two years. Patients with a score of 18 or more on the sub-clinical positive symptoms items (45 items in total) will be assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS. The primary outcome is the transition rate to psychosis according to the CAARMS-criteria. Group differences will be analysed with chi-square tests and survival analyses.DiscussionCBT is a highly tolerated treatment. The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State (ARMS) are distressed by odd disturbing experiences. Giving explanations for and normalising these experiences may reduce the arousal (distress) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis.Screening the entire help-seeking population referred to community mental health services with a two-stage strategy, as compared with traditional referral to a specialist clinical psychosis centre, might detect more ultra-high-risk (UHR) patients. This type of screening could be implemented in mental health care as routine screening. The trial is registered at Current Controlled trials as trial number ISRCTN21353122.

Depression and social anxiety in help-seeking patients with an ultra- high risk for developing psychosis

Knowledge on associations between ultra-high risk (UHR) for developing psychosis and on non-psychotic psychopathology in help-seeking populations is limited with respect to differences between male and female patients. The present study tests the hypothesis that both social anxiety and depression are highly prevalent in an UHR population, particularly among women. From February 2008 to February 2010 baseline data were collected from help-seeking subjects (14-35 years) who were included in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial. Two recruiting strategies were used: a two-stage screening strategy in a population of consecutive help-seeking and distressed subjects of secondary mental health services, and a referral strategy. This study included 201 patients with a mean age of 22.7 years. Of these, 102 (51%) were female, 58% of the patients met the criteria for clinical depression on the Beck Depression Inventory and 42% met the criteria for clinical social phobia on the Social Interaction Anxiety Scale. Women showed more depression and social anxiety than men. The results support the hypothesis that UHR is associated with depression and social anxiety, particularly in women. Screening a help-seeking population with depression and anxiety may be effective in detecting patients at UHR for developing psychosis.

Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis

BACKGROUND Previous research has established the relationship between cannabis use and psychotic disorders. Whether cannabis use is related to transition to psychosis in patients at ultra-high risk (UHR) for psychosis remains unclear. The present study aimed to review the existing evidence on the association between cannabis use and transition to psychosis in UHR samples. METHOD A search of PsychInfo, Embase and Medline was conducted from 1996 to August 2015. The search yielded 5559 potentially relevant articles that were selected on title and abstract. Subsequently 36 articles were screened on full text for eligibility. Two random-effects meta-analyses were performed. First, we compared transition rates to psychosis of UHR individuals with lifetime cannabis use with non-cannabis-using UHR individuals. Second, we compared transition rates of UHR individuals with a current DSM-IV cannabis abuse or dependence diagnosis with lifetime users and non-using UHR individuals. RESULTS We found seven prospective studies reporting on lifetime cannabis use in UHR subjects (n = 1171). Of these studies, five also examined current cannabis abuse or dependence. Lifetime cannabis use was not significantly associated with transition to psychosis [odds ratio (OR) 1.14, 95% confidence interval (CI) 0.856-1.524, p = 0.37]. A second meta-analysis yielded an OR of 1.75 (95% CI 1.135-2.710, p = 0.01), indicating a significant association between current cannabis abuse or dependence and transition to psychosis. CONCLUSIONS Our results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose-response relationship between current cannabis use and transition to psychosis.

Four-Year Follow-up of Cognitive Behavioral Therapy in Persons at Ultra-High Risk for Developing Psychosis : The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial

BACKGROUND Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline. METHOD The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated. RESULTS The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up. CONCLUSIONS CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases. TRIAL REGISTRATION The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (http://controlled-trials.com/ISRCTN21353122/gaag).

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis

BACKGROUND Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). METHOD In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. RESULTS Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. CONCLUSIONS The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episode.

The effect of childhood adversity on 4-year outcome in individuals at ultra high risk for psychosis in the Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial

Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients.

Four-Year Cost-effectiveness of Cognitive Behavior Therapy for Preventing First-episode Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial

Background This study aims to evaluate the long-term cost-effectiveness of add-on cognitive behavior therapy (CBT) for the prevention of psychosis for individuals at ultrahigh risk (UHR) of psychosis. Method The Dutch Early Detection and Intervention randomized controlled trial was used, comparing routine care (RC; n = 101) with routine care plus CBT for UHR (here called CBTuhr; n = 95). A cost-effectiveness analysis was conducted with treatment response (defined as proportion of averted transitions to psychosis) as an outcome and a cost-utility analysis with quality-adjusted life years (QALYs) gained as a secondary outcome. Results The proportion of averted transitions to psychosis was significantly higher in the CBTuhr condition (with a risk difference of 0.122; b = 1.324, SEb = 0.017, z = 7.99, P < 0.001). CBTuhr showed an 83% probability of being more effective and less costly than RC by -US