Wulf Rössler

Early recognition of high risk of bipolar disorder and psychosis: an overview of the ZInEP "early recognition" study

Early detection of persons with first signs of emerging psychosis is regarded as a promising strategy to reduce the burden of the disease. In recent years, there has been increasing interest in early detection of psychosis and bipolar disorders, with a clear need for sufficient sample sizes in prospective research. The underlying brain network disturbances in individuals at risk or with a prodrome are complex and yet not well known. This paper provides the rationale and design of a prospective longitudinal study focused on at-risk states of psychosis and bipolar disorder. The study is carried out within the context of the Zurich Program for Sustainable Development of Mental Health services (Zürcher Impulsprogramm zur Nachhaltigen Entwicklung der Psychiatrie). Persons at risk for psychosis or bipolar disorder between 13 and 35u2009years of age are examined by using a multi-level-approach (psychopathology, neuropsychology, genetics, electrophysiology, sociophysiology, magnetic resonance imaging, near-infrared spectroscopy). The included adolescents and young adults have four follow-ups at 6, 12, 24, and 36u2009months. This approach provides data for a better understanding of the relevant mechanisms involved in the onset of psychosis and bipolar disorder, which can serve as targets for future interventions. But for daily clinical practice a practicable “early recognition” approach is required. The results of this study will be useful to identify the strongest predictors and to delineate a prediction model.

Neurocognitive profiles in help-seeking individuals: comparison of risk for psychosis and bipolar disorder criteria.

BACKGROUNDnNeurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains.nnnMETHODnThis study included 207 help-seeking individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar disorder (HRBip; n = 30), who were compared with persons comprising a matched, healthy control group (CG; n = 50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses.nnnRESULTSnThe performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p = 0.01).nnnCONCLUSIONSnPerformances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itself.

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses.

BACKGROUNDnNeurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period.nnnMETHODnData were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d.xa0=xa01.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory.nnnRESULTSnNeurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations.nnnCONCLUSIONSnOur data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness.

Adolescents and adults at clinical high-risk for psychosis: age-related differences in attenuated positive symptoms syndrome prevalence and entanglement with basic symptoms.

BACKGROUNDnThe attenuated positive symptoms syndrome (APSS) is considered an at-risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under-researched.nnnMETHODnBased on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13-17, 18-22 and 23-35 years age groups.nnnRESULTSnOf 175 individuals (age = 20.6 ± 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 ± 5.0 v. 23.2 ± 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11-0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups.nnnCONCLUSIONSnAPSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents.

Prediction Analysis for Transition to Schizophrenia in Individuals at Clinical High Risk for Psychosis: The Relationship of DAO, DAOA, and NRG1 Variants with Negative Symptoms and Cognitive Deficits

Schizophrenia is characterized by positive and negative symptoms and cognitive dysfunction. The glutamate hypothesis of schizophrenia has been hypothesized to explain the negative symptoms and cognitive deficits better than the dopamine hypothesis alone. Therefore, we aimed to evaluate whether glutamatergic variants such as d-amino acid oxidase (DAO), DAO activator (DAOA)/G72, and neuregulin 1 (NRG1) single-nucleotide polymorphisms (SNPs) and their mRNA levels predicted (i) transition to schizophrenia spectrum disorders and (ii) research domain criteria (RDoC) domains, mainly negative valence and cognitive systems. In a 3-year prospective study cohort of 185 individuals (age: 13–35u2009years) at high risk and ultra-high risk (UHR) for psychosis, we assessed DAO (rs3918347, rs4623951), DAOA (rs778293, rs3916971, rs746187), and NRG1 (rs10503929) SNPs and their mRNA expression. Furthermore, we investigated their association with RDoC domains, mainly negative valence (e.g., anxiety, hopelessness) and cognitive (e.g., perception disturbances, disorganized symptoms) systems. NRG1 rs10503929 CCu2009+u2009CT versus TT genotype carriers experienced significantly more disorganized symptoms. DAOA rs746187 CC versus CTu2009+u2009TT genotype, DAOA rs3916971 TT versus TCu2009+u2009CC genotype, and DAO rs3918347 GAu2009+u2009AA versus GG genotype carriers experienced nominally more hopelessness, visual perception disturbances, and auditory perception disturbances, respectively. The schizophrenia risk G-allele of DAO rs3918347 nominally increased risk for those UHR individuals with attenuated positive symptoms syndrome. No association between DAO, DAOA, NRG1 SNPs, and conversion to schizophrenia spectrum disorders was observed. Our findings suggest that DAO, DAOA, and NRG1 polymorphisms might influence both RDoC negative valence and cognitive systems, but not transition to schizophrenia spectrum disorders.

Neuregulin 1 (NRG1) gene expression predicts functional outcomes in individuals at clinical high-risk for psychosis

Little is known about valid predictive markers for functional outcomes in an at-risk for psychosis population. In a cohort of 185 individuals (age: 13-35 years) at high risk (HR) and ultra-high risk (UHR), we assessed pan-NRG1 mRNA levels across good functional status (GFS) and poor functional status (PFS) at baseline, and good functional outcome (GFO) and poor functional outcome (PFO) at 12-month follow-up. NRG1 mRNA levels were significantly higher in individuals with PFO than individuals with GFO at 12-month follow-up. Our findings suggest that NRG1 might emerge as a predictive marker for functional outcomes in at-risk for psychosis population.

Methodik der Kostenanalyse in der Versorgung psychisch Kranker

Die okonomischen Standardmethoden zur Wirtschaftlichkeitsbewertung von Gutern und Leistungen gehen davon aus, das diese Guter und Leistungen durch uber den Markt gelenkte Ein- und Auszahlungsstrome charakterisiert sind (Buchholz & Eichhorn 1987). Dies ist das klassische Marktmodell. Ihm liegt die Vorstellung zugrunde, das durch die in freier Konkurrenz wirkenden Krafte von Angebot und Nachfrage eine annahernd effiziente Verteilung von Guter und Leistungen auf dem Markt erzwingen. Solchen Bedingungen gehorchende Waren, Guter oder Leistungen werden als marktfahig bezeichnet, da sie zu einem bestimmten Preis sowohl angeboten als auch nachgefragt werden (Kriedel 1980). Damit ist gleichzeitig der monetare Charakter der Hauptkriterien fur die Wirtschaftlichkeitsbeurteilung solcher Guter festgelegt.