Carolien Zeetsen

121 CHAPTER Cognitive i mpairments in patients with GUD predict relapse 6 effects of GHB in the brain (Xie & Smart, 1992; Castelli et al., 2000; Carter et al., 2009). GHB–induced comas have also been suggested to affect hippocampal activity, both in humans (Raposo Pereira et al., 2018a) and animals (Johansson et al., 2014), which could also contribute to the observed memory problems. Since memory is a broad concept, with various sub domains (e.g. working memory, long–term memory, declarative memory, etc), future studies should explore which specific memory domains are most affected in patients with GUD. Despite several studies suggesting that cognitive impairment in patients with GUD might be caused by GHB–induced comas (Raposo Pereira et al., 2018b) the current study did not observe a relationship between the number of self–reported GHB–induced comas and cognitive impairment. Several methodological limitations hamper strong conclusions concerning the (causal) relationship between GHB–induced coma and cognitive impairment. First, studies, including ours, commonly rely on self–reported comas where a clear definition of what constitutes a coma (or if a coma is for instance a short blackout) is lacking. A detailed and reliable account of the total number of GHB–induced comas is therefore hard to obtain. But also due to comas usually occurring on a daily basis (Beurmanjer et al., 2019), amnesia as this might be an aspect of GHB–induced coma itself (Sumnall et al., 2008), and the observed memory impairment in patients with GUD. Second, as seen in other samples, patients with GUD often also use other substances. These might also contribute to cognitive impairment in these patients. Finally, it may also be that it is not the number of GHB–induced comas or substance use levels that contribute to cognitive impairment. Similar to patients with other SUD (Bruijnen, Dijkstra, et al., 2019) our data did not find a relationship between cognitive performance on the MoCA and years of regular use, dose, severity of dependence and comas. This suggests that other factors might be involved, for instance lack of sleep, malnutrition or other psychiatric or somatic comorbidities. Future studies should explore mechanisms contributing to cognitive impairment in patients with GUD and other SUD. The current study shows that MoCA performance, in particular on the memory domain, were associated with the risk of relapse. This is in line with studies in other SUD, such as alcohol (Czapla et al., 2015), cocaine (Turner et al., 2009) and opioids (Ma et al., 2019), where cognitive impairment is associated with the risk of relapse and poor treatment retention. Cognitive functions are crucial to direct behaviour and obtain control over impulses and emotions (Loughead et al., 2015), including substance use. Cognitive impairment in patients with SUD (including GUD) might thus interfere with taking control of substance use, to change behaviour, and reach treatment goals (Stevens et al., 2014; Loughead et al., 2015). SUD patients with cognitive impairment might require treatment adaptations focussing on cognitive enhancement (Verdejo–García, 2016; Rensen et al., 2019). Indeed, several studies