Associations between disturbed sleep and attenuated psychotic experiences in people at clinical high risk for psychosis.

BACKGROUND: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. METHODS: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. RESULTS: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. CONCLUSION: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

[Linguistic distance and psychosis in ethnic minorities]. / Taalachterstand en psychose onder mensen met een migratieachtergrond.

BACKGROUND: Ethnic minorities in the Netherlands face an excess psychosis risk, and understanding of causality remains limited. Linguistic disadvantage and other indicators of societal exclusion might play a role, and offer potential targets for public health interventions. AIM: To establish the contribution of linguistic disadvantage, indicators of social distance and perceived discrimination to the increased risk of psychoses in migrants and ethnic minorities. METHODS: We used the Dutch data from an international case-control study into psychotic disorders (the EU-GEI study). A first episode of psychosis was our outcome variable, and we used well-defined data on established confounders (e.g. age and sex) and indicators of ethnicity, social distance, linguistic disadvantage and perceived discrimination as our predictor variables. RESULTS: Ethnic minorities face an increased psychosis risk. This appears to be the case for both first- and second- generation migrants and so-called ‘Western’ and non-Western migrants. Though confounders and social distance appear to contribute, linguistic disadvantage appears to play a role in the excess psychosis risk in first-generation migrants. CONCLUSION: Reducing the social consequences of linguistic disadvantage or social distance might be a starting point for concrete public health interventions aimed at preventing the increased psychosis risk faced by first-generation migrants.

[The neglected 'self' in schizophrenia]. / Het veronachtzaamde 'zelf' bij schizofrenie.

BACKGROUND: Although self-disorders are common in schizophrenia, little attention is paid to them in clinical practice. AIM: To provide an overview of the knowledge regarding self-disorders in schizophrenia in the context of diagnosis and treatment. METHOD: A description of the literature on the history, background, diagnosis and treatment of self-disorders in schizophrenia. RESULTS: From a phenomenological perspective, disturbances in the minimal self frequently occur in schizophrenia. Two self-disorders are described: decreased self-affection (reduced sense of ownership of experiences, reduced sense of authorship of actions) and hyperreflexivity (normally self-evident experiences receive disproportionate attention). Self-disorders are common in schizophrenia, but also in other psychiatric classifications. Partly due to the emphasis on reliability of DSM-5 classifications, there is limited interest in the self-disorders. Treatment focused on physical and social activity can probably enhance the basic sense of self. In addition, hyperreflexivity may be reduced by interventions aimed at acceptance, while targeting so-called erroneous cognitions may possibly worsen hyperreflexivity. CONCLUSION: Self-disorders in schizophrenia are common and insufficient attention is paid to self-disorders in research and clinical practice. More knowledge about self-disorders might lead to new insights into therapeutic options in schizophrenia.

[The Personal Antipsychotic Choice Index]. / De Persoonlijke Antipsychotica Keuzewijzer.

BACKGROUND: More than half of the patients suffering from a first psychotic episode withdraw from antipsychotic medication within the first year of treatment. Shared decision making could enhance the therapeutic relationship and thus adherence. AIM: To describe an online decision aid for the selection of antipsychotic medication: the Personal Antipsychotic Choice Index (www.pakwijzer.nl). METHOD: Per effect and side effect, the 15 most commonly prescribed antipsychotics in the Netherlands have been ranked on the basis of data on the magnitude of a desired effect and the chance of a side effect, based on a systematic literature study. We assigned scores to antipsychotics for each desired and undesired effect and processed these scores in an algorithm. A personal ranking of antipsychotics is calculated based on the value that patients attach to these effects. RESULTS: These desired and undesired criteria used are rated in the PACindex: effectiveness concerning psychotic, depressive and cognitive symptoms, weight gain, sexual dysfunction, drowsiness, hypersomnia, extrapyramidal symptoms, anticholinergic adverse effects, hypersalivation, nausea, dizziness, energy loss, blunted affect/less need for companionship. High level evidence was available for ranking weight gain, sexual dysfunction, menstrual disorders, extrapyramidal symptoms and effectiveness on psychotic symptoms. We used lower level evidence ranking the remaining criteria. CONCLUSION: A ready applicable online choixe index for the use of an antipsychotic agent has been developed and put into use. The PACindex could be updated when new evidence of new antipsychotics became available..

[Oxidative stress in psychosis: a new target for intervention?] / Oxidatieve stress bij psychotische stoornissen: een nieuw target voor interventie?

BACKGROUND: Oxidative stress is a state of imbalance between reactive oxidants and anti-oxidants. Oxidative stress and a disrupted redox regulation in the brain might contribute to the pathophysiology of psychotic disorders and could serve as interesting new targets for clinical intervention. Advanced glycation end products (AGEs) in the skin can be measured non-invasively and indicate cumulative oxidative stress. AIM: To investigate cross-sectional and longitudinal differences in AGE-levels in patients with recent onset psychosis (patients) and healthy controls (controls). To investigate association of AGE-levels and brain volume in psychosis. METHOD: An autofluorescence measurement of AGEs in the skin was performed in patients and controls. AGEs were compared in patients and controls. Furthermore, the association between AGEs and volumes of the amygdala, hippocampus and total cortical gray matter was investigated in patients. RESULTS: AGEs in the skin were elevated by 15% (or 0.66 standard deviations) in patients (n = 86) compared to controls (n = 135) (p < 0.001). An indication of a higher AGE-accumulation rate (p = 0.07) was found in patients (n = 66) compared to controls (n = 160). We found a negative association between AGEs in the skin and hippocampus volume (standardized beta= 0.27; p = 0.03) in patients (n = 46). CONCLUSION: Findings of a high level of AGEs in the skin indicate excessive oxidative stress in patients with recent onset psychosis.

[The importance of inter-rater reliability in psychopharmacological trials]. / Het belang van interbeoordelaars­betrouwbaarheid in psychofarmacologisch onderzoek.

BACKGROUND: There are concerns about the declining efficacy of antidepressants and antipsychotics in clinical trials. A potential cause may be found in poor training practices to achieve sufficient inter-rater reliability (IRR). However, it is unknown whether IRR and training procedures are currently reported. AIM: To determine the proportion of publications concerning double-blind randomized controlled trials (RCTs) investigating antipsychotics or antidepressants that report IRR and training procedures. METHOD: We extracted all double-blind RCTs from five large meta-analyses concerning antidepressants and antipsychotics. Further, we conducted a Medline-search for double-blind RCTs investigating antidepressants from January 2016 - January 2020, and antipsychotics from January 2000 - January 2019. RESULTS: In 179 double-blind RCTs with antidepressants, only 4.5% reported an IRR coefficient whereas 27.9% reported on training procedures. Further, in 207 double-blind RCTs with antipsychotics, 11.2% reported an IRR coefficient and 34.8% reported training procedures. CONCLUSION: There is a substantial lack of reporting IRR and training procedures in RCTs with antidepressants and antipsychotics. Considering the implications of insufficient IRR, it is necessary to conduct and report training procedures and IRR. Reporting IRR and training procedures should be made mandatory by editorial boards of scientific journals.

[The underrepresentation of complex patient groups in scientific research: ethical considerations]. / De ondervertegenwoordiging van complexe patiëntengroepen in wetenschappelijk onderzoek: ethische overwegingen.

BACKGROUND: Subgroups of patients with severe mental illness are underrepresented in scientific research. One of the possible causes is the fact that in these patient groups barriers may exist to the giving of competent informed consent. AIM: Describing the ethical dilemmas that may occur when conducting research with these patient groups. METHOD: We present an overview of the Dutch legislation and regulation concerning participation in scientific research, and discuss the ethical dilemmas that arise in the mentioned patient groups. We present four directions for solutions. RESULTS: In research with these patient groups more attention is needed for the explicit assessment and enhancement of competence. For the subgroup that is persistently incompetent, the possibilities of doing research with existing patient data without informed consent, need further exploration. CONCLUSION: Further legislative development is needed for research with patients with severe mental illness who are persistently incompetent. Herein, it is crucial to involve ethicists and organizations representing patients' and relatives' perspectives.

[Implementation of a stop-smoking support program for patients and employees in a psychiatric hospital: First results]. / Implementatie van een stoppen-met-rokenprogramma in een psychiatrisch ziekenhuis: eerste resultaten.

BACKGROUND: In contrast to several other countries, smoking is not an integral part of treatment during admission to a psychiatric hospital in The Netherlands.
AIM: Implementation of a smoking cessation program for patients and employees of a psychiatric ward of an academic medical center in The Netherlands.
METHOD: Prospective, mixed-method study of implementation of a smoking cessation program for patients and employees of a psychiatric academic hospital in Amsterdam. The program consisted of 7 weekly group meetings by certified smoking cessation coaches. Nicotine replacement therapy was provided for free, if necessary.
RESULTS: During 14 months, 65 individuals were seeking help to stop smoking: 39 patients and 26 employees. Of these, 29 patients and 16 employees participated in group meetings with an average of 2.6 times per person. There were 20 individuals who visited the group meetings or received individual coaching at least 3 times (6 patients and 14 employees). Fifty-five percent of these individuals reported to be smoke-free at 3 months after joining the first meeting. Employees were much more likely to quit than patients. From interviews with 20 participants, it was noticed that combining patients and employees in one group was perceived as a barrier due to a gap in processing speed.
CONCLUSION: On the psychiatric ward of an academic hospital in The Netherlands, there was a positive experience with providing smoking cessation treatment. A small number of employees and patients participated in a smoking cessation program and quitting smoking was reached by only a few patients. Supporting smoking cessation in a psychiatric hospital asks for intensive screening, diagnosing, treatment and smoke-free policies.

Effect of preoperative biliary drainage on cholestasis-associated inflammatory and fibrotic gene signatures in perihilar cholangiocarcinoma.

Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis. Drainage affects inflammatory and fibrotic gene signatures.

[Personalised medicine for psychosis]. / Personalised medicine bij psychotische stoornissen.

BACKGROUND: Personalised medicine (pm) means treatment that specifically targets the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics.
AIM: To update our knowledge about the current use of pm in the treatment of psychotic disorders.
METHOD: Review of the literature on pm for psychoses.
RESULTS: At the moment, genetic and other biological characteristics cannot be used for the diagnosis and treatment of psychotic disorders because they are not sensitive enough and their specificity is too low. We investigated immunulogical, oxidative, metabolic, hormonal and dopaminergic aspects that could lead to the use of pm. pm is already being used on the basis of phenotypical, cognitive and psychosocial characteristics; those characteristics include substance abuse, cognitive dysfunction, ethnicity and childhood trauma.
CONCLUSION: In the next years there may be more opportunities for using for pm in psychosis. The increase may results from large genetic network studies and treatment studies involving stratification based on hypothetical specific mechanisms instead of on the categorical diagnosis of illnesses such as schizophrenia.

Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.

BACKGROUND: In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine. METHOD: Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S). RESULTS: Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects. CONCLUSIONS: In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis.

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I 2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.

Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

[Smoking cessation and schizophrenia]. / Stoppen met roken en schizofrenie.

BACKGROUND: People with schizophrenia smoke about 5.6 times as much as people without the disease. This factor is a major but treatable cause of morbidity and mortality in this patient population. Nevertheless, health professionals make relatively little effort to discourage people from smoking or to give it up altogether.
AIM: To increase health professionals' knowledge about possible therapeutic interventions that can help people with schizophrenia to stop smoking.
METHOD: We studied the relevant literature.
RESULTS: Many people with schizophrenia do in fact want to give up smoking. However, many health professionals are reluctant to intervene because, as a result, people with schizophrenia might experience a deterioration in their mental state. We believe that people with schizophrenia who are determined to give up smoking need to receive a combination of pharmacotherapy and psychological support. This patient population requires a longer than normal period of treatment.
CONCLUSION: So far, a combination of bupropion, nicotine patches and psychological support has proved the most effective form of support for this target group consisting of people with schizophrenia.

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. METHOD: Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. RESULTS: When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. CONCLUSIONS: In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

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.

Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis.

BACKGROUND: Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors. METHOD: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC. RESULTS: Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA. CONCLUSIONS: UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

Longitudinal association between cognitive performance and obsessive-compulsive symptoms in patients with psychosis and unaffected siblings.

OBJECTIVE: Obsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning. METHOD: Baseline and follow-up data from 622 patients and 670 un-affected siblings from the 'Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains. RESULTS: Cross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS. CONCLUSION: Although insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed.