A multi-perspective approach to early detection of psychosis

Background: Early detection of psychosis has been a highly investigated field of research in the last 20 years. However, decreasing transition rates show the need for further markers to improve prediction of transition of those with a potential risk of developing psychosis. Methods: In the present doctoral thesis I aimed at improving early detection of psychosis by using a multimodal approach. Therefore, neurocognition, (potential) biological markers namely serum and plasma BDNF (study 1) and, prolactin (study 2), and psychopathology (study 3) were investigated. At-risk mental state (ARMS), first-episode psychosis (FEP), and in one study also chronic schizophrenia (CS) patients were recruited. Furthermore, a special focus was on potential gender differences because knowledge about these differences can lead to improved early detection and treatment. Results: Altered BDNF levels were found, with lowest in ARMS, intermediate in FEP, and highest in CS. Plasma BDNF correlated positively with executive functioning. Also, prolactin levels were found to be altered in antipsychotic naïve ARMS and FEP patients, with hyperprolactinemia being more frequent in women compared to men in both groups even after correction for the normal biological variation. Lastly, small gender differences were found in very first self-perceived symptoms with women reporting more frequently anxiety and (sub-threshold) hallucinations and men more often cognitive and negative symptoms. Discussion: Taken together the altered levels in the investigated biological markers are promising and might contribute to the improvement of early detection of psychosis. The observed small gender differences in psychopathology match previous results. A multimodal approach combining the different known predictors of psychosis is promising but more research is needed before the above named biological markers can be included in such a model

Individualized metacognitive therapy for delusions: A randomized controlled rater-blind study

Theory-driven interventions targeting specific factors that contribute to delusions are receiving increased interest. The present study aimed to assess the efficacy of individualized metacognitive therapy (MCT+), a short manualized intervention that addresses delusion-associated cognitive biases.; 92 patients with current or past delusions were randomized to receive 12 twice-weekly sessions of either MCT+ or a control intervention within a randomized controlled rater-blind design. Psychopathology and cognitive biases were assessed at baseline, 6 weeks and 6 months. ANCOVAs adjusted for baseline scores were used to assess differences between groups regarding outcome variables. Both per-protocol and intention-to-treat analyses were conducted.; At 6 weeks, there was a significant difference in favor of MCT+ regarding decrease in delusion severity and improvement of self-reflectiveness (medium effect size), and a trend-wise difference regarding probability thresholds to decision. These effects increased, when only patients attending a minimum of 4 therapy sessions were considered. Control group patients subsequently showed further improvement while patients in the MCT+ group remained stable, such that there were no differences between groups at the 6-month follow-up.; Lower attendance rates in the control group possibly leading to unequal therapeutic effort; lower baseline delusion severity in the MCT+ group.; The result pattern suggests that MCT+ led to earlier improvement in delusions and cognitive biases compared to the control intervention. The absence of a long-term effect might reflect floor effects in the MCT+ group, but may also indicate the need for further measures to promote sustainability of MCT+ effects

The Frankfurt Complaint Questionnaire for self-assessment of basic symptoms in the early detection of psychosis-Factor structure, reliability, and predictive validity

OBJECTIVES: Patients with schizophrenia often experience subtle disturbances in several domains of information processing-so-called basic symptoms (BS). BS are already present before onset of frank psychosis and can be assessed by interviews but also by the self-administered Frankfurt Complaint Questionnaire (FCQ). We investigated the factor structure, reliability, and predictive validity for transition to psychosis of the FCQ, comparing previously proposed factor solutions containing 1, 2, 4, and 10 factors. METHODS: Confirmatory factor analysis was used in a sample of 117 at-risk mental state and 92 first-episode psychosis participants of the Basel FePsy (early detection of psychosis) study. RESULTS: Although all factor models fitted to the data, the 2- or 4-factor solutions performed best among the models that used at least half of the FCQ items, suggesting the covariance between FCQ items is best explained by 2 to 4 underlying factors. No FCQ-scale predicted transition to psychosis. CONCLUSION: We could confirm a 2- to 4-factor structure of the FCQ in a sample of at-risk mental state and first-episode psychosis patients using confirmatory factor analysis. Contrary to interview-assessed cognitive-perceptive BS, self-assessed BS do not seem to improve prediction of psychosis. This result reinforces reports of poor correspondence between interview- and questionnaire-assessed BS

Pourquoi et comment soigner plus précocement les troubles psychotiques?

Chronic psychosis, as for instance schizophrenia, usually begins in young adulthood and may cause severe disability. It causes a mean loss of life expectancy of 22 years. Actual models of psychosis do not trace the beginning of psychosis to the first franc psychotic episode only, but to earlier symptoms. In a classical health system only considering the first psychotic episode, the mean duration of untreated illness (DUI) can last several years. Yet this DUI has a direct impact on the prognosis of the disease. Actual international recommendations prescribe to early detect and treat at risk mental states of psychosis, thus reducing DUI. Such an attitude also helps the patient to integrate care in a moment where she/he is fully in condition to consent and to adhere. Generalist practitioners are crucial actors of early detection. We describe here simple and standardized tools helping early detection of high-risk mental states of psychosis in primary care and the appropriate attitude to do it properly. Numerous countries have developed early detection and treatment centers for psychosis. It has been established that such interventions clearly decrease the risk of transition towards chronic psychosis and improve the prognosis. These recent data about early detection and intervention in psychosis are a major step forward in psychiatry practice. It is now necessary to largely develop such actions in France

The relationship between negative symptoms and cognitive functioning in patients at clinical high risk for psychosis

Negative symptoms and neurocognitive performance have been reported to be negatively associated in patients with emerging psychosis. However, most previous studies focused on patients with frank psychosis and did not differentiate between subdomains of negative symptoms. Hence, we aimed to elucidate the specific relationship between negative symptoms and cognitive functioning in patients at clinical high risk (CHR) for psychosis. Data from 154 CHR patients collected within the prospective Früherkennung von Psychosen (FePsy) study were analyzed. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive functioning with an extensive neuropsychological test battery. Regression analyses revealed significant negative associations between negative symptoms and cognitive functioning, particularly in the domains of nonverbal intelligence and verbal fluency. When analyzing each negative symptom domain separately, alogia and asociality/anhedonia were significantly negatively associated with nonverbal intelligence and alogia additionally with verbal fluency. Overall, our results in CHR patients are similar to those reported in patients with frank psychosis. The strong negative association between verbal fluency and negative symptoms may be indicative of an overlap between these constructs. Verbal fluency might have a strong influence on the clinical impression of negative symptoms (particularly alogia) and vice versa

Evaluating verbal learning and memory in patients with an at-risk mental state or first episode psychosis using structural equation modelling

Verbal learning and memory are impaired not only in patients with a first episode of psychosis (FEP) but also-to a lower extent-in those with an at-risk mental state for psychosis (ARMS). However, little is known about the specific nature of these impairments. Hence, we aimed to study learning and memory processes in ARMS and FEP patients by making use of structural equation modelling.; Verbal learning was assessed with the California Verbal Learning Test (CVLT) in 98 FEP patients, 126 ARMS patients and 68 healthy controls (HC) as part of the Basel early detection of psychosis (FePsy) study. The four-factorial CFA model of Donders was used to estimate test performance on latent variables of the CVLT and growth curve analysis was used to model the learning curve. The latter allows disentangling initial recall, which is strongly determined by attentional processes, from the learning rate.; The CFA model revealed that ARMS and FEP patients were impaired in Attention Span, Learning Efficiency and Delayed Memory and that FEP patients were additionally impaired in Inaccurate Memory. Additionally, ARMS-NT, but not ARMS-T, performed significantly worse than HC on Learning Efficiency. The growth curve model indicated that FEP patients were impaired in both initial recall and learning rate and that ARMS patients were only impaired in the learning rate.; Since impairments were more pronounced in the learning rate than the initial recall, our results suggest that the lower scores in the CVLT reported in previous studies are more strongly driven by impairments in the rate of learning than by attentional processes

Can neuropsychological testing facilitate differential diagnosis between at-risk mental state (ARMS) for psychosis and adult attention-deficit/hyperactivity disorder (ADHD)?

Background: Patients with an at-risk mental state (ARMS) for psychosis and patients with attention-deficit/hyperactivity disorder (ADHD) have many overlapping signs and symptoms and hence can be difficult to differentiate clinically. The aim of this study was to investigate whether the differential diagnosis between ARMS and adult ADHD could be improved by neuropsychological testing. Methods 168 ARMS patients, 123 adult ADHD patients and 109 healthy controls (HC) were recruited via specialized clinics of the University of Basel Psychiatric Hospital. Sustained attention and impulsivity were tested with the Continuous Performance Test, verbal learning and memory with the California Verbal Learning Test, and problem solving abilities with the Tower of Hanoi Task. Group differences in neuropsychological performance were analyzed using generalized linear models. Furthermore, to investigate whether adult ADHD and ARMS can be correctly classified based on the pattern of cognitive deficits, machine learning (i.e. random forests) was applied. Results Compared to HC, both patient groups showed deficits in attention and impulsivity and verbal learning and memory. However, in adult ADHD patients the deficits were comparatively larger. Accordingly, a machine learning model predicted group membership based on the individual neurocognitive performance profile with good accuracy (AUC = 0.82). Conclusions Our results are in line with current meta-analyses reporting that impairments in the domains of attention and verbal learning are of medium effect size in adult ADHD and of small effect size in ARMS patients and suggest that measures of these domains can be exploited to improve the differential diagnosis between adult ADHD and ARMS patients

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis