Neuropsychological performance in patients with substance use disorder with and without mood disorders

Background: Mood disorders commonly co-occur in patients with substance use disorders (SUD). This combination may increase the risk of pathological effects and impair cognitive functioning. Aim: The aim of the study was to examine the effects of mood and substance use disorders on specific neuropsychological measures. Methods: The participants comprised 164 hospitalised patients, 88 with (SUD + MD) and 76 (SUD-MD) without mood disorders, ranging in age from 19 to 65 years. Their diagnostic assessment was based on a psychiatric interview (ICD-10). Neuropsychological tests were carried out after a minimum of one month of abstinence. Results: Processing speed (p = 0.029), and perceptual reasoning (p = 0.039) were more impaired in the SUD + MD group than in the SUD-MD group. An Analysis of covariance (ANCOVA) controlled for age, education level, learning difficulties and polysubstance use revealed that the groups were most powerfully separated by the Digit Symbol test and the Block Design test. Conclusions: Patients with substance abuse and mood disorders seem to have more deficits in speed processing and perceptual reasoning than substance abuse patients without mood disorders. These processing speed difficulties and perceptual problems may impact prognosis and treatment. The Digit Symbol test and the Block Design test are a fast and sensitive ways to examine treatment effectiveness and monitor treatment progress.</p

Selection bias in clinical studies of first-episode psychosis: A follow-up study

Objectives: Selection bias is a concern in studies on psychotic disorders due to high dropout rates and many eligibility criteria for inclusion. We studied how representative the first-episode psychosis study sample in the Turku Early Psychosis Study (TEPS) was.Methods: We screened 3772 consecutive admissions to the clinical psychiatric services of Turku Psychiatry, Finland, between October 2011 and June 2016. A total of 193 subjects had first-episode psychosis and were suitable for TEPS. Out of 193 subjects, 101 participated (PA) and 92 did not participate (NPA) in TEPS due to refusal or contact problems. We retrospectively used patient register data to study whether NPA and PA groups differed in terms of clinical outcomes during 1-year follow-up.Results: In overall sample, the NPA group had a significantly higher rate of discontinuation of clinical treatment than the PA group (48.9 % vs 29.7 %, p = 0.01). In the hospital-treated subsample chi-square tests did not indicate statistically significant differences between the NPA and PA groups in the rate of involuntary care (69.7 % vs 62.7 %, p = 0.34), coercive measures (36.0 % vs 22.7 %, p = 0.06), and readmissions during the follow-up (41.5 % vs 33.8 %, p = 0.31), respectively.Conclusion: The differences in clinical outcomes and treatment characteristics in the non-participating and participating groups were relatively modest. The results do not support a major sample selection bias that would complicate the interpretation of results in this first-episode psychosis study.</p

Metabolic trajectories in childhood and adolescence: Effects on risk for schizophrenia

Abnormal glucose and lipid metabolism is common in antipsychotic-naive first-episode patients with schizophrenia, but it is unclear whether these changes can already be seen in premorbid or prodromal period, before the first psychotic episode. We examined insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride trajectories in children and adolescents (9-18 years old), who were later diagnosed with schizophrenia, any non-affective psychosis (NAP) or affective disorder (AD). The study population consisted of a general population-based cohort "The Cardiovascular Risk in Young Finns Study", started in 1980 (n=3596). Psychiatric diagnoses were derived from the Health Care Register up to the year 2018. Multivariate statistical analysis indicated no significant differences in insulin or lipid levels in children and adolescents who later developed schizophrenia (n=41) compared to the cohort control group (n=3202). In addition, no changes in these parameters were seen in the NAP (n=74) or AD (n=156) groups compared to the controls, but lower triglyceride levels in childhood/adolescence associated with earlier diagnosis of psychotic disorder in the NAP group. Taken together, our results do not support any gross-level insulin or lipid changes during childhood and adolescence in individuals with later diagnosis of schizophrenia-spectrum disorder. Since changes in glucose and lipid metabolism can be observed in neuroleptic-naive patients with schizophrenia, we hypothesize that the more marked metabolic changes develop during the prodrome closer to the onset of the first psychotic episode. The findings have relevance for studies on developmental hypotheses of schizophrenia.</p

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (N-spared = 40, N-impaired = 13). Impaired patients showed significantly increased negative symptomatology (p(fdr) = 0.003), reduced cognitive performance (p(fdr) < 0.001) and general functioning (p(fdr) < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease

Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models' ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40-64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND.: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS.: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS.: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS.: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.status: Published onlin

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.status: publishe