Cognitive change in psychosis

Background: Cognitive functioning is impaired in schizophrenia spectrum disorders, with cognitive symptoms a core part of schizophrenia. Cognitive impairment is associated with poorer daily life functioning and prognosis, making it an important treatment goal. As opposed to positive symptoms, cognitive symptoms have proven quite resistant to antipsychotic drug treatment. It is also unclear how cognitive functioning changes throughout the course of psychosis, from the prodromal stage, during acute psychosis and after the onset of medical treatment. The aim of this thesis was to investigate cognitive impairment and change during these three important stages of illness. Paper I aimed to investigate the relation between cognitive and symptomatic change in patients with psychotic disorders (n=84) during the early acute phase of illness. Psychotic symptoms in the sample were due to schizophrenia spectrum disorders (F20-29), psychoactive substance use (F12-19), and affective disorders with psychosis (F31-33). We administered the RBANS neurocognitive test battery on admission and again at acute ward discharge (mean time 4.1 weeks, SD 1.86 weeks), using PANSS to assess symptomatic change. We found cognitive impairment (t < 35) in 28.6% of participants at baseline and 13.1% at follow-up. PANSS negative symptoms change significantly predicted total RBANS performance improvement (beta = -.307, p = .016). There was no significant difference in cognitive change between subjects with schizophrenia and those with other psychotic disorders. Findings thus indicated that the proportion of subjects with mild to moderate impairment in cognitive test performance is reduced across the acute phase of psychosis, and that improvement is related to amelioration of negative symptoms. Paper II compared the cognitive functioning and profile of UHR subjects (n=51) to a sample with schizophrenia (F20), split into two groups based on duration of illness (n=19 and 22). Comparisons were made using coordinated norms based on healthy controls (n=61) reflecting the younger UHR age spectrum. A comprehensive neurocognitive test battery aiming to measure speed of processing, working memory, verbal learning, reasoning, and problem solving, as well as visual problem solving were used. UHR subjects showed impaired speed of processing (p3 years for speed of processing and working memory (both p<.001). There were no significant differences in performance between the UHR group and the group with duration of schizophrenia < 3 years. It can be concluded that cognitive performance is impaired in UHR subjects and should thus be monitored by clinicians. If spatial skills are less impaired, this could be useful to know when facilitating academic and work participation for this group. Paper III compared cognitive change in three groups of participants with schizophrenia spectrum disorder (F20-F29) receiving amisulpride (n=33), aripiprazole (n=32), and olanzapine (n=39) over 12 months. A short neurocognitive test battery was administered at baseline and again at 6, 26 and 52 weeks. Sample average cognitive test t-scores improved from 42.20 to 46.39 over the year, rising significantly to 6 (Δ2.0; p= .002), 26 (Δ3.4; p< .001) and 52 (Δ4.2; p< .001) weeks, corresponding to a medium effect size Cohen’s d of .53. There were no significant between-drug changes in the amount of improvement. Nor were there any significant differences in change between subjects with schizophrenia and those with other psychotic disorders. Our findings thus indicate that despite significant improvements in cognitive test performance, there were no significant between-drug differences in cognitive change in the 12 months following onset of a new course of treatment. Conclusion: The findings from the present thesis suggest that cognitive impairment in psychosis is present before the appearance of positive symptoms, with a similar but less severe profile of impairment than in established psychotic disorders. Cognitive impairment appears to fluctuate alongside the course of psychosis, with improvement seen during the first weeks of treatment in acute psychosis, and further improvement with the onset of medical treatment

Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups.publishedVersio

Trajectories of psychological distress during recovery from polysubstance use disorder

Introduction: Polysubstance use is a prevalent substance use pattern with adverse effects on psychological distress and diminished treatment outcomes. Although polysubstance use often dominates clinical practice, the trajectories of substance use and psychological distress in the initial phase of treatment have been subject to few empirical investigations. Material and Methods: 141 patients initiating inpatient or outpatient treatment for substance use disorder were followed for 12 months, using multiple assessments. We assessed psychological distress and substance use at baseline and at 3-, 6-, and 12-month follow-up visits. We implemented an SMS tracker of substance use during follow-up to reduce the impact of missing data. Results: Stable abstinence was associated with a lower baseline SCL-90-R score, as well as a more rapid symptomatic decline during the first 3 months of abstinence. Unstable abstinence was associated with higher GSI scores at baseline, but also with a significant drop in scores across the follow-up period. Relapse was associated with an initial drop in GSI scores, but a subsequent increase in GSI scores at later follow-ups. Conclusions: Most participants had a rapid reduction of psychological distress during the first 3 months of abstinence. Elevated levels of psychological distress may indicate an increased risk of drug use or relapse and should be monitored carefully. Our findings highlight the importance of early screening for psychological distress in SUD treatment, and advocate the use of tentative diagnostic procedures in the early phase of treatment of PSUD.publishedVersio

Does childhood trauma influence cognitive functioning in schizophrenia? The association of childhood trauma and cognition in schizophrenia spectrum disorders.

Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect

Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients with Schizophrenia Spectrum Disorders: A Secondary Outcome Analysis of a Pragmatic, Randomized Trial (BeSt InTro)

Background Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum. Methods Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling. Results Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization. Conclusions There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.publishedVersio

Wanting to do Just Anything Else: A Q-Methodological Step Towards Defining Boredom

Boredom is a commonly reported phenomenon with apparent ecological validity which remains under-researched and poorly defined by academic literature. This study used Q methodology in moving towards a unifying conceptual understanding of how people perceive boredom, thereby improving the foundation for further research and for the creation of valid measuring instruments for both state and trait boredom. The sample consisted of 10 Norwegian students (aged 19-26) and 10 seniors (aged 61-89). All completed a 40-statement Q-sort task, with data subjected to an inverse factor analysis using the PQMethod computer software. Results identified three factors to the students' perception of boredom: Active boredom, boredom coping, and passified boredom, with aspects of restlessness and disengagement from a current task common to all factors. Elderly people appeared to be markedly less prone to boredom than were students, and possible reasons for this are also discussed

Cognitive change in psychosis

Background: Cognitive functioning is impaired in schizophrenia spectrum disorders, with cognitive symptoms a core part of schizophrenia. Cognitive impairment is associated with poorer daily life functioning and prognosis, making it an important treatment goal. As opposed to positive symptoms, cognitive symptoms have proven quite resistant to antipsychotic drug treatment. It is also unclear how cognitive functioning changes throughout the course of psychosis, from the prodromal stage, during acute psychosis and after the onset of medical treatment. The aim of this thesis was to investigate cognitive impairment and change during these three important stages of illness. Paper I aimed to investigate the relation between cognitive and symptomatic change in patients with psychotic disorders (n=84) during the early acute phase of illness. Psychotic symptoms in the sample were due to schizophrenia spectrum disorders (F20-29), psychoactive substance use (F12-19), and affective disorders with psychosis (F31-33). We administered the RBANS neurocognitive test battery on admission and again at acute ward discharge (mean time 4.1 weeks, SD 1.86 weeks), using PANSS to assess symptomatic change. We found cognitive impairment (t < 35) in 28.6% of participants at baseline and 13.1% at follow-up. PANSS negative symptoms change significantly predicted total RBANS performance improvement (beta = -.307, p = .016). There was no significant difference in cognitive change between subjects with schizophrenia and those with other psychotic disorders. Findings thus indicated that the proportion of subjects with mild to moderate impairment in cognitive test performance is reduced across the acute phase of psychosis, and that improvement is related to amelioration of negative symptoms. Paper II compared the cognitive functioning and profile of UHR subjects (n=51) to a sample with schizophrenia (F20), split into two groups based on duration of illness (n=19 and 22). Comparisons were made using coordinated norms based on healthy controls (n=61) reflecting the younger UHR age spectrum. A comprehensive neurocognitive test battery aiming to measure speed of processing, working memory, verbal learning, reasoning, and problem solving, as well as visual problem solving were used. UHR subjects showed impaired speed of processing (p3 years for speed of processing and working memory (both p<.001). There were no significant differences in performance between the UHR group and the group with duration of schizophrenia < 3 years. It can be concluded that cognitive performance is impaired in UHR subjects and should thus be monitored by clinicians. If spatial skills are less impaired, this could be useful to know when facilitating academic and work participation for this group. Paper III compared cognitive change in three groups of participants with schizophrenia spectrum disorder (F20-F29) receiving amisulpride (n=33), aripiprazole (n=32), and olanzapine (n=39) over 12 months. A short neurocognitive test battery was administered at baseline and again at 6, 26 and 52 weeks. Sample average cognitive test t-scores improved from 42.20 to 46.39 over the year, rising significantly to 6 (Δ2.0; p= .002), 26 (Δ3.4; p< .001) and 52 (Δ4.2; p< .001) weeks, corresponding to a medium effect size Cohen’s d of .53. There were no significant between-drug changes in the amount of improvement. Nor were there any significant differences in change between subjects with schizophrenia and those with other psychotic disorders. Our findings thus indicate that despite significant improvements in cognitive test performance, there were no significant between-drug differences in cognitive change in the 12 months following onset of a new course of treatment. Conclusion: The findings from the present thesis suggest that cognitive impairment in psychosis is present before the appearance of positive symptoms, with a similar but less severe profile of impairment than in established psychotic disorders. Cognitive impairment appears to fluctuate alongside the course of psychosis, with improvement seen during the first weeks of treatment in acute psychosis, and further improvement with the onset of medical treatment

Handwriting versus Keyboard Writing: Effect on Word Recall

The objective of this study was to explore effects of writing modality on word recall and recognition. The following three writing modalities were used: handwriting with pen on paper; typewriting on a conventional laptop keyboard; and typewriting on an iPad touch keyboard. Thirty-six females aged 19-54 years participated in a fully counterbalanced within-subjects experimental design. Using a wordlist paradigm, participants were instructed to write down words (one list per writing modality) read out loud to them, in the three writing modalities. Memory for words written using handwriting, a conventional keyboard and a virtual iPad keyboard was assessed using oral free recall and recognition. The data was analyzed using non-parametric statistics. Results show that there was an omnibus effect of writing modality and follow-up analyses showed that, for the free recall measure, participants had significantly better free recall of words written in the handwriting condition, compared to both keyboard writing conditions. There was no effect of writing modality in the recognition condition. This indicates that, with respect to aspects of word recall, there may be certain cognitive benefits to handwriting which may not be fully retained in keyboard writing. Cognitive and educational implications of this finding are discussed

Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups

Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group.This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants.The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups