Comorbid substance abuse in first-episode schizophrenia: Effects on cognition and psychopathology in the EUFEST study
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.
Section snippets
Study design
The EUFEST study design is described in detail elsewhere (Kahn et al., 2008). In brief, a total of 50 centers participated in 13 European countries and Israel. To be eligible for inclusion, patients (18–40 years) had to meet DSM-IV criteria for schizophrenia, schizophreniform, or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview Plus (MINI +) (Sheehan et al., 1998). Exclusion criteria were i) more than two years had passed since the onset of positive
Results
In the total sample of 498 patients 31.1% reported SUD or AUD according to DSM-IV criteria, 22.2% of patients used cannabis, 7.6% solely cannabis, 5.4% in combination with alcohol, 5.2% in combination with other illegal substances (mainly amphetamines, XTC and cocaine), and 4.0% in combination with both. Two patients (0.4%) reported no consumption of cannabis while using illegal substances, 2 patients (0.4%) used illegal substances in combination with alcohol and 8.0% of patients had only
Discussion
In a previous analysis neurocognitive measures at baseline were compared between the EUFEST patients and two-hundred-twenty healthy control subjects showing reduced performance of patients on all tests (Galderisi et al., 2009). The aims of the presented analysis were to investigate the impact of concomitant substance abuse on psychopathology and neuropsychological functions in schizophrenia patients in the early stages of the disorder. Studies to date addressing this question and including only
Role of funding source
This study was supported by the European Group for Research in Schizophrenia (EGRIS; Utrecht, the Netherlands) with grants from 3 pharmaceutical companies: AstraZeneca (Södertälje, Sweden), Pfizer (New York, NY), and Sanofi-Aventis (Paris, France).
The EUFEST has been registered by Current Controlled Trials Ltd and assigned the number ISRCTN68736636 (http://www.controlled-trials.com/ ISRCTN68736636).
Contributors
T.W. wrote the manuscript. WW.F., RS.K., and EM.D. were strongly involved in the design of the study. All the authors, except A.H. and TS.-A. performed the measurements and the ratings, and generated the source data. T.S.-A. undertook the statistical analysis. A.H., and EM.D. contributed to the literature searches, and all the authors contributed to the interpretation of the data. All authors contributed to and have approved the final manuscript.
Conflict of interest
T. Wobrock was honorary speaker for Alpine Biomed, AstraZeneca, Bristol Myers Squibb, Eli Lilly, I3G, Janssen Cilag, Novartis, Lundbeck, Sanofi-Aventis and Pfizer, and has accepted travel or hospitality not related to a speaking engagement from AstraZeneca, Bristol-Myers-Squibb, Eli Lilly, Janssen Cilag, and Sanofi-Synthelabo; and has received a research grant from AstraZeneca, I3G and AOK (health insurance company).
P. Falkai was honorary speaker for Janssen-Cilag, Astra-Zeneca, Lilly, BMS,
Acknowledgments
None.
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2020, Schizophrenia ResearchCitation Excerpt :While the majority of people use combinations of a variety of different substances, the most common is the combined use of alcohol and cannabis (Lambert et al., 2005; Crockford and Addington, 2017). SUD can have significant negative effects on the course and prognosis of psychotic disorders (Lambert et al., 2005; Crockford and Addington, 2017), although there is interstudy variability (e.g. Wobrock et al., 2013). Before first contact, SUD is associated with a longer duration of untreated psychosis (DUP) and lower treatment utilization.
From apathy to addiction: Insights from neurology and psychiatry
2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Consistent with the “self-medication hypothesis” (Awad and Voruganti, 2015; Khantzian, 1997), it is possible that substance abuse improves negative symptoms at the cost of increasing positive symptoms. Indeed, Wobrock and colleagues found trend-level lower negative symptoms after 6-months (p = 0.075) in patients with schizophrenia and substance use disorder compared to those without (Wobrock et al., 2013). However, this effect was not observed when analysis was restricted only to schizophrenia patients with recent initiation of substance abuse (i.e. excluding those with lifetime diagnosis).