The impact of lifetime polysubstance use on clinical, cognitive, and neuroimaging measures in psychosis
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Abstract
INTRODUCTION: Substance use disorders often accompany psychosis spectrum disorders. Additionally, polysubstance use has been linked to increase severity in clinical symptoms, particularly positive symptoms (Talamo et al., 2006). While the literature on substance use and its effects on symptoms in psychosis has shown consistent results, literature pertaining to the effects of substance use on cognition are mixed (Potvin et al., 2008). Unexpectedly, some studies suggest that individuals with psychosis and substance use disorders perform better on certain cognitive tasks than individuals with psychosis who do not have a substance use disorder (Joyal et al., 2003). However, many of these studies are limited by small sample sizes. Here, we aim to investigate the effects of lifetime polysubstance use on clinical, cognitive, and neuroimaging measures using data from the second wave of a large multisite study of psychosis spectrum disorders called the Bipolar and Schizophrenia Network for Intermediate Phenotypes 2 (BSNIP-2). We predict an increase severity in clinical symptoms (particularly positive symptoms), worse cognitive performance, gray matter volume (GMV) reduction, subcortical GMV reduction, and decreases in gray matter (GM) thickness in those with a greater history of polysubstance use.
METHODS: In psychosis patients with a diagnosis of schizophrenia, schizoaffective disorder or psychotic bipolar disorder, frequency and prevalence of lifetime substance use of 7 different categories (cannabis, stimulants, cocaine, alcohol, hallucinogens, opioids, and other substances) were quantified through standard clinical interviews. Three groups were derived using a composite score reflecting severity of lifetime polysubstance use (low = 187, mid = 371, high = 186). Clinical and cognitive measures were obtained through the Positive and Negative Syndrome Scale (PANSS), Montgomery-Asperg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Barratt Impulsivity Scale-11 (BIS-11), Clinical Anxiety Scale (CAS) and Brief Assessment of Cognition in Schizophrenia (BACS) in a cohort of 744 individuals with psychosis spectrum disorders. Neuroimaging measures were obtained through Magnetic Resonance Imaging (MRI) in a sample of 492 individuals with psychosis. Group contrasts were performed between "low", "mid", and "high" groups and multiple comparison correction was performed using False Discovery Rate threshold of p<0.05. All findings were controlled for age, sex, race, socioeconomic status, and psychosis diagnosis. Neuroimaging findings also controlled for site and total estimated intracranial volume (ICV).
RESULTS: A total of 744 psychosis patients were used for the analysis on clinical and cognitive measures, and 492 psychosis patients were used for neuroimaging measures. The group with the greatest lifetime history of polysubstance use ("high") had an overall elevated severity of total symptoms on the PANSS (psychosis), MADRS (depression), YMRS (mania), and BIS-11 (impulsiveness). For the post hoc analysis of PANSS, MADRS, YMRS, and BIS-11 subscale scores, significant differences were consistently found between the "high" and "low" group. However, severity of negative symptoms and CAS symptoms were not significantly different between any of the groups. For overall cognitive performance (BACS), the group with the greatest lifetime history of polysubstance use performed significantly better than both "mid" and "low" lifetime polysubstance use. Post hoc tests examining BACS cognitive subdomains demonstrated that the "high" group performed significantly better than both "mid" and "low" groups on 4 out of the 6 tests: Digit Sequencing, Symbol Coding, Tower of London, and Verbal Fluency. Surprisingly, neuroimaging measures were not different between groups for total GMV, subcortical GMV, GM thickness, GM area, and ICV.
DISCUSSION: We found clinical symptoms, as measured by the PANSS, MADRS, YMRS, and BIS-11 to be more severe in individuals with a greater lifetime history of polysubstance use. Our study reveals that a greater history of polysubstance use does not worsen cognitive impairments in patients with psychosis, and instead that higher cognitive performance might be a risk factor for greater substance use in patients with psychosis. Environmental factors, such as socioeconomic class, might be mitigating this higher cognitive performance and future research is warranted.
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