Comorbid substance abuse in first-episode schizophrenia: Effects on cognition and psychopathology in the EUFEST study

Abstract

Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients.

Method

In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N = 119, consisting of N = 88 patients with persisting SUD at baseline and N = 31 patients with previous SUD) and without SUD (FE-non-SUD, N = 204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding.

Results

In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p = 0.033, Cohen's d = 0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p = 0.008, Cohen's d = 0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption.

Conclusions

FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.

Introduction

Cognitive deficits can be considered as a core deficit of schizophrenia and have been found even in untreated, first-episode patients (Heinrichs and Zakzanis, 1998, Torrey, 2002). These impairments account for significant variance in measures of functional status (Green, 1996) and cognitive functioning is a correlate of global and specific functional outcome in schizophrenia and contributes to poor judgment and lack of insight (Jensen et al., 2004).

Substance abuse in individuals with schizophrenia is the most prevalent comorbid psychiatric condition with life-time prevalence between 10 and 65% (Kovasznay et al., 1997, Buckley et al., 2009) and has been associated with elevated positive symptoms (Soyka et al., 2001), lower negative symptoms (Soyka et al., 2001), and reduced positive and negative symptoms (Dixon et al., 1991).

Substance abuse and dependence (substance use disorder, SUD) are associated with deleterious consequences on cognitive functioning. This is frequently reported for patients abusing alcohol and cocaine (Beatty et al., 1995), but is also described in patients with long-term cannabis abuse (Pope et al., 1995).

Despite the high prevalence of comorbid SUD in schizophrenia, knowledge about the influence of substance abuse on neurocognitive function is still limited and various studies revealed inconclusive results (Coulston et al., 2007). In some studies patients with comorbid SUD (mainly cocaine and alcohol) presented greater cognitive deficits than patients without substance abuse, in other studies no differences between users and nonusers or even better performance of patients with concomitant SUD have been demonstrated (Coulston et al., 2007). In a meta-analysis, subjects with schizophrenia and comorbid substance abuse displayed similar cognitive performance as schizophrenia patients without substance abuse (Yucel et al., 2012). In a further meta-analysis focussing on the effects of cannabis on neurocognition in schizophrenia cannabis-using patients performed better than patients with no history of cannabis use with small to medium effect sizes (Rabin et al., 2011). A recent study including nearly thousand patients with non-affective psychosis found that lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition while current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Meijer et al., 2012).

One should note that most studies included only patients with a chronic disease course and a long duration of illness, but first-episode and recent onset patients haven't been investigated extensively (Yucel et al., 2012). In a comparison of first-episode patients with and without previous cannabis abuse, comorbid patients demonstrated slightly better (Wobrock et al., 2007), showed significant superior cognitive performance in visual memory, working memory and executive functioning (Yucel et al., 2012), had better attention and executive functions (Rodriguez-Sanchez et al., 2010) or demonstrated better cognitive task performance on all measures except working memory manipulation (Leeson et al., 2012).

The aim of this post-hoc analysis of the EUFEST study was to examine the impact of comorbid substance abuse on neurocognition in this large sample of first-episode patients. Additionally, the subgroups with and without comorbid SUD were compared in terms of positive, negative and depressive psychopathology and extrapyramidal motor symptoms. The mentioned variables were compared at baseline and 6-months follow-up to evaluate the stability or variability of cognitive and clinical patterns in both subgroups over time.