Cannabis Use and Cognition in Schizophrenia

People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patient group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis

Left Temporal Lobe Structural and Functional Abnormality Underlying Auditory Hallucinations in Schizophrenia

In this article, we have reviewed recent findings from our laboratory, originally presented in Hugdahl et al. (2008). These findings reveal that auditory hallucinations in schizophrenia should best be conceptualized as internally generated speech mis-representations lateralized to the left superior temporal gyrus and sulcus, not cognitively suppressed due to enhanced attention to the ‘voices’ and failure of fronto-parietal executive control functions. An overview of diagnostic questionnaires for scoring of symptoms is presented together with a review of behavioral, structural, and functional MRI data. Functional imaging data have either shown increased or decreased activation depending on whether patients have been presented an external stimulus during scanning. Structural imaging data have shown reduction of grey matter density and volume in the same areas in the temporal lobe. We have proposed a model for the understanding of auditory hallucinations that trace the origin of auditory hallucinations to neuronal abnormality in the speech areas in the left temporal lobe, which is not suppressed by volitional cognitive control processes, due to dysfunctional fronto-parietal executive cortical networks

Sexual Dysfunction and Hyperprolactinemia in Male Psychotic Inpatients: A Cross-Sectional Study

Introduction. Sexual dysfunction (SD) and hyperprolactinemia are frequently reported in patients with psychotic disorders and have the potential for severe complications but investigations in males are particularly scarce. The primary aims were to determine the prevalence of SD and hyperprolactinemia in male patients and to investigate whether associations exist between SD and prolactin levels. Methods. Cross-sectional data were obtained at discharge from the hospital or 6 weeks after admittance for patients acutely admitted for psychosis and treated with a second-generation antipsychotic drug. Results. Half the patients reported diminished sexual desire and more than a third reported erectile and ejaculatory dysfunctions with no differences among the drugs. More than half the sample was hyperprolactinemic. No association was found between prolactin levels and SD. Conclusion. High rates of SD and hyperprolactinemia were found in male patients and should be a treatment target. SD and hyperprolactinemia were not correlated

Cognitive profile in ultra high risk for psychosis and schizophrenia: A comparison using coordinated norms

Background: Cognitive impairment is not only a core aspect of schizophrenia but also commonly observed in help-seeking youth at ultra high risk for psychosis (UHR), with potential implications for prognosis and individualized treatment. However, there is no consensus on the cognitive profile in the UHR state, partly due to lack of valid comparisons of performance in established schizophrenia and UHR. Objectives: To compare the cognitive functioning and profile of UHR subjects to a sample with schizophrenia, they were split into two groups based on duration of illness. Comparisons were made using coordinated norms based on healthy controls reflecting the younger UHR age spectrum. Methods: Participants for UHR (n = 51) and schizophrenia groups (n = 19 and n = 22) were included from the Prevention of Psychosis and Bergen Psychosis 2 projects. All subjects completed 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. Cognitive functioning was compared between groups based on coordinated norms using z-scores derived by regression modeling from an age-matched healthy control group (n = 61). Results: UHR subjects showed significantly impaired speed of processing (p 3 years for speed of processing and working memory (both p < 0.001). There were no significant differences in performance between the UHR group and the group with duration of schizophrenia <3 years. Conclusion: Cognitive performance is impaired in UHR subjects as compared to healthy controls and should thus be monitored when a person is deemed at high risk of psychotic illness. Spatial skills, as measured by tests using physical objects, appear less affected than other domains. The pattern of impairment is similar to that of a group with recent onset schizophrenia but is less severe than in a group with duration of illness <3 years.publishedVersio

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

Akathisia and atypical antipsychotics. Relation to suicidality, agitation and depression in a clinical trial

Objective: Akathisia is among the most unpleasant side effects related to antipsychotic drug (AP) use, and possible associations between akathisia and agitation, depression and suicidal behaviour, respectively, have been described in previous literature. New generation antipsychotics are however regarded less prone to induce this particular adverse effect compared to older drugs, but evidence is incomplete and in need of confirmation from clinically relevant samples and settings. We, therefore, aim to investigate akathisia at hospital discharge for patients consecutively admitted with acute-phase psychosis and treated with atypical antipsychotics according to guideline-concordant clinical practice. Methods: This exploratory study is part of a naturalistic randomised controlled study in patients admitted with acute phase psychosis (N = 109). We report cross-sectional data at discharge/first follow-up after acute psychiatric hospital admission for patients with schizophrenia and related psychotic disorders. Results: There were statistically significant positive associations between akathisia and the following; suicidality in men (Beta 0.306, p = 0.048), but not in women; agitation in those previously unexposed to antipsychotics (Beta 0.288, p = 0.047) and depression in those exposed to antipsychotics before hospital admittance (Beta 0.375, p = 0.031). Conclusion: Main findings were that akathisia is still a prevalent side effect in a clinically relevant sample of patients treated with atypical antipsychotics. Our results suggest that akathisia is significantly associated with depression, suicidality and agitation in different subgroups of patients receiving APs. Akathisia can be detrimental and the relations between akathisia and depression, suicidality and agitation should be investigated further in prospective, hypothesis-testing studies with larger samples.publishedVersio

Dynamic Functional Connectivity Patterns in Schizophrenia and the Relationship With Hallucinations

There is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed information on connectivity abnormalities in psychiatric disorders such as schizophrenia. The current study investigated dynamic FC in a sample of 80 schizophrenia patients and 80 matched healthy control subjects, replicating previous findings of aberrant dwell times in specific FC states, and further supporting a role for default mode network (DMN) dysfunction. Furthermore, relationships with hallucinations, a core symptom of schizophrenia, were explored. Two measures of hallucinations were used, one measure of current hallucination severity assessed on the day of scanning, and one trait-measure where hallucinations were assessed repeatedly over the course of 1 year. Current hallucination severity did not show a significant relationship with dynamic FC. However, the trait-measure of hallucination proneness over 1 year showed a significant relationship with dynamic FC. Patients with high hallucination proneness spent less time in connectivity states characterized by strong anti-correlation between the DMN and task-positive networks. The findings support theoretical models of hallucinations which have proposed an instability of the DMN and impaired cognitive control in patients with hallucinations. Furthermore, the results point to hallucination proneness as a potential marker for identifying distinct subgroups of schizophrenia patients.publishedVersio

Illicit substances detected through high-resolution MS analysis in urine samples are associated with greater symptom burden in patients with psychosis

Background The prevalence of new psychoactive substances (NPS) in acute psychotic patients has not been investigated systematically. We applied a highly sensitive and specific mass spectrometry method for detection of NPS as well as traditional drugs of abuse (including illicit or prescription substances) in order to assess their prevalence and associations with symptom severity. Identification of these substances is useful in both the diagnostic process and evaluation of treatment effects. Methods Demographic data, results from the Positive and Negative Syndrome Score (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) and urine samples from admission were collected from 53 patients recruited into a clinical study of psychosis during 2014-2017. Urine samples were analysed with liquid chromatography high resolution mass spectrometry (LC-QTOF-MS), through both highly specific detection of 191 substances using internal standards and untargeted screening by means of pre-defined libraries. PANSS and CDSS scores in patients with or without drugs of abuse were compared. Results Potential drugs of abuse, i.e. drugs that could be used in a controlled therapeutic or a non-prescribed manner, were detected in samples from 20 of the 53 patients. Seven samples contained illicit drugs, but no NPS were detected. In this small patient subgroup, PANSS total score and CDSS score were significantly higher than in patients with negative urine sample results. Conclusion Drug screening could play an important role in the differential diagnostic evaluation of patients admitted with psychotic symptoms. Although no NPS were detected in the study population, we found other substances that were associated with psychotic and depressive symptoms.publishedVersio

White matter microstructural differences between hallucinating and non-hallucinating schizophrenia spectrum patients

The relation between auditory verbal hallucinations (AVH) and white matter has been studied, but results are still inconsistent. This inconsistency may be related to having only a single time-point of AVH assessment in many studies, not capturing that AVH severity fluctuates over time. In the current study, AVH fluctuations were captured by utilizing a longitudinal design and using repeated (Positive and Negative Symptoms Scale) PANSS questionnaire interviews over a 12 month period. We used a Magnetic Resonance Diffusion Tensor Imaging (MR DTI) sequence and tract-based spatial statistics (TBSS) to explore white matter differences between two subtypes of schizophrenia patients; 44 hallucinating (AVH+) and 13 non-hallucinating (AVH-), compared to 13 AVH- matched controls and 44 AVH+ matched controls. Additionally, we tested for hemispheric fractional anisotropy (FA) asymmetry between the groups. Significant widespread FA-value reduction was found in the AVH+ group in comparison to the AVH- group. Although not significant, the extracted FA-values for the control group were in between the two patient groups, for all clusters. We also found a significant difference in FA-asymmetry between the AVH+ and AVH- groups in two clusters, with significantly higher leftward asymmetry in the AVH- group. The current findings suggest a possible qualitative difference in white matter integrity between AVH+ and AVH- patients. Strengths and limitations of the study are discussed.publishedVersio

Auditory Hallucinations in Schizophrenia: The Role of Cognitive, Brain Structural and Genetic Disturbances in the Left Temporal Lobe

In this article we review research in our laboratory on auditory hallucinations using behavioral and MRI measure. The review consists of both previously published and new data that for the first time is presented together in a cohesive way. Auditory hallucinations are among the most common symptoms in schizophrenia, affecting more than 70% of the patients. We here advance the hypothesis that auditory hallucinations are internally generated speech perceptions that are lateralized to the left temporal lobe, in the peri-Sylvian region. From this we predict that hallucinating patients should have problems identifying a simultaneously presented external speech sound, as measured through performance on the dichotic listening (DL) paradigm with consonant–vowel syllables, since this technique lateralizes the stimulus input. Across a series of behavioral experiments, we have shown that patients with schizophrenia who experience frequent auditory hallucinations fail to demonstrate an expected right ear advantage on the dichotic listening test. Absence of a right ear advantage is indicative of a functional deficit in the left peri-Sylvian region. The results also revealed that patients with ongoing auditory hallucinations were more impaired than patients with previous hallucinations, and that a higher score on the hallucination item in a standard symptom rating scale (BPRS) correlated negatively with number of correct reports for the right ear stimulus. Moreover, we have found that schizophrenia patients fail to shift attention to the left ear stimulus, when explicitly instructed to focus on the right or left ear stimulus only, thus showing a deficit in inhibition of attention and response-inhibition. The behavioral DL data are substantiated in two MR morphometry studies that revealed significant reductions in grey matter density in the left peri-Sylvian region in hallucinating patients, and patients with reduced left temporal lobe grey matter density. Hallucinating patients also failed to show a right ear advantage in the dichotic listening test. Ongoing fMRI studies are focused on the underlying synaptic and molecular mechanisms by investigating the effects of the glutamate antagonist drug memantine on auditory perception and speech lateralization, and examination of temporal cortex-specific gene expression in the left peri-Sylvian region