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A Meta-Analysis of Executive Dysfunction in Patients With Psychiatry Research 272 (2019) 230–236 Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres Review article A meta-analysis of executive dysfunction in patients with schizophrenia: Different degree of impairment in the ecological subdomains of the T Behavioural Assessment of the Dysexecutive Syndrome ⁎ Maria Lotus Thaia, Anna Krogh Andreassenb,c, Vibeke Blikstedb,c,d, a OPUS, Outpatient Clinic for Young People with Schizophrenia, Aalborg University Hospital, Psychiatry Department, Brandevej 5, 9220 Aalborg Ø, Denmark b Psychosis Research Unit, Aarhus University Hospital Psychiatry, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark c Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark d Interacting Minds Centre, Aarhus University, Jens Chr. Skous Vej 4, 8000 Aarhus C, Denmark ARTICLE INFO ABSTRACT Keywords: We performed meta-analyses of studies using the 6 subtests of the neuropsychological test battery, the Problem solving Behavioural Assessment of the Dysexecutive Syndrome (BADS), in order to assess and compare subdomains of Planning executive dysfunction in stable phase patients with schizophrenia relative to healthy controls. The meta-analyses fl Cognitive exibility were performed according to the PRISMA statement. A systematic literature search was performed yielding 10 Inhibition studies for inclusion (N = 375; N = 541). Meta-analyses were done using Stata IC 14. Due to large het- Organizing SCH HC erogeneity and the few number of studies a random-effects model was used along with Hedges’ g. Results showed that relative to healthy controls, patients with schizophrenia overall performed significantly worse in all subtests of BADS. However, moderate effect sizes were seen with regard to temporal estimation and strategy-forming, while very large effect sizes were seen regarding complex forward planning, inhibition, cognitive flexibility and novel problem solving. The findings from this meta-analysis demonstrate a significant difference between pa- tients with (primarily) longer lasting schizophrenia and healthy control subjects on all subdomains of executive functions (EF). But some aspects of EF seem to be more severely affected than others. Future research and clinical interventions need to differentiate between subdomains of EF. 1. Introduction mechanisms of the executive deficits in patients with schizophrenia, e.g. rule generation and selection, and dynamic adjustments in control A considerable amount of empirical research has attempted to chart (Kerns et al., 2008). Processing of rules involves: the dorsolateral re- the area of neurocognitive functioning in schizophrenia (SZ). Several gions of the prefrontal cortex (DLPFC) (sustaining maintenance of goal meta-analyses and systematic reviews (Bowie et al., 2006; Harvey et al., or rule information), subcortical systems in the basal ganglia (con- 2005; Heinrichs and Zakzanis, 1998; Mesholam-Gately et al., 2009; tributing to selective rule updating by "Go" and "NoGo" neurons), and Reichenberg and Harvey, 2007) consistently show that moderate to neurotransmitters involved in a gate mechanism in the DLPFC such as severe impairments characterize patients with SZ across the seven dopamine D1 receptors (involved in closing the gate and securing stable cognitive domains included in the MATRICS Consensus Cognitive Bat- maintenance), and dopamine D2 receptors (involved in rapid up- tery such as IQ, attention, learning, visual and verbal memory, lan- dating). Furthermore, norepenephrine is involved in interference con- guage, and executive function (Fatouros-Bergman et al., 2014; trol mechanisms in PFC, and norepinephrine and N-methyl d-aspartate Fioravanti et al., 2012; Fioravanti et al., 2005; Nuechterlein et al., receptors are thought to be of significant importance in rule selection 2008). It is a robust finding that executive dysfunction represents one of (Kerns et al., 2008). The ability to adjust behaviour and cognition si- the most frequent and manifest neurocognitive impairments in schizo- multaneously based on an ongoing performance is referred to as dy- phrenia (Fatouros-Bergman et al., 2014; Heinrichs and Zakzanis, 1998; namic adjustments in control. This process involves the dorsal anterior Johnson-Selfridge and Zalewski, 2001; Raffard and Bayard, 2012; cingulate cortex (ACC) (performance monitoring) in close interaction Reichenberg and Harvey, 2007; Aas et al., 2014). Cognitive neu- with other brain areas such as DLPFC, basal ganglia, and the locus roscience has provided models that explain some of the component coeruleus by dopaminergic input contributing to various processes of ⁎ Corresponding author at: Palle Juul-Jensens Boulevard 99, Indgang K, Plan 5, K510-104, DK-8200 Aarhus N, Denmark. E-mail address: [email protected] (V. Bliksted). https://doi.org/10.1016/j.psychres.2018.12.088 Received 5 April 2018; Received in revised form 14 December 2018 Available online 20 December 2018 0165-1781/ © 2018 Elsevier B.V. All rights reserved. M.L. Thai et al. Psychiatry Research 272 (2019) 230–236 error monitoring (Kerns et al., 2008). Studies have found reduced validity and task simplification regarding EF assessment, a British re- DLPFC gray matter volume in patients with schizophrenia dominated search group developed a test battery, ‘The Behavioural Assessment of by comprehensive deficit in executive functions (Orellana and the Dysexecutive Syndrome (BADS)’ with the aim of measuring EF Slachevsky, 2013). Furthermore, it has been shown that patients with impairment with tasks resembling everyday life activities requiring EF schizophrenia have altered neural activity in the DLPFC, ACC and the (Evans et al., 1997; Norris and Tate, 2000; Wilson et al., 1997,1998). mediodorsal nucleus of the thalamus, while at the same time showing According to this research group, an advantage of BADS is that it increased activity in other areas of the PFC, which might be due to consists of six subtests tapping several different aspects of EF compensatory mechanisms (Orellana and Slachevsky, 2013). Finally, (Wilson et al., 1998) which is consistent with the fractionation ap- neuroimaging has revealed abnormal connectivity in the three fronto- proach to executive dysfunction (Raffard and Bayard, 2012). The BADS cortical circuits that are involved in cognitive and behavioural control was originally developed to detect executive dysfunction in patients (the DLPCF, orbitofrontal cortex (OFC), and ACC) in patients with with traumatic brain-injuries and other neurological disorders schizophrenia (Orellana and Slachevsky, 2013). The EF deficits seen in (Wilson et al., 1998). However, the initial studies compared brain-in- patients with schizophrenia could be seen as part of the overall neu- jured samples to both patients with longer lasting SZ and healthy rodevelopmental hypothesis suggesting that interactions between en- controls. In both studies, the patient groups were significantly impaired vironmental and genetic factors during critical stages of early brain on most subtests of BADS relative to healthy controls, but the differ- development underlies later development of schizophrenia (Fatemi and ences between patients with SZ and the patients with brain-injuries Folsom, 2009). were non-significant (Evans et al., 1997; Wilson et al., 1998). Only The definition of the term executive functions (EF) lacks consensus. Wilson et al. (1998) found a significant difference between patient In addition, several researchers agree that a common theoretical ground groups on a subtest of BADS, i.e., Zoo Map. Moreover, the only non- for the construct is missing (Barkley, 2012; Jurado and Rosselli, 2007; significant difference between patients with longer lasting SZ and Savla et al., 2010). In spite of this lack of consent, the concept of EF is controls was found on Temporal Judgment. often described as an umbrella term covering a diverse set of cognitive So far, no publication has attempted to complete a systematic capacities to guide, monitor, and control our actions and mental pro- overview of findings from studies using subtests of BADS to assess ex- cesses to meet particular goals in a purposeful manner. Executive ecutive dysfunction in schizophrenia. This meta-analysis was performed functions (EF) may be defined as higher-order neurocognitive functions in order to make a statistical summarization of studies that compare the consisting of abilities to plan and structure goal-directed activity and performance of patients with SZ and healthy controls using BADS. By problem-solving behaviour in a strategic, flexible manner or as merely producing separate meta-analyses of each BADS subtest, we aim to shed the ability to respond in an adaptive way to novel situations (Chan further light on whether SZ is better characterized by a general ex- et al., 2008; Diamond, 2013; Jacques and Marcovitch, 2010; Jurado ecutive dysfunction or by deficits in specific EF components. The BADS and Rosselli, 2007; Katz et al., 2007). These complex cognitive pro- was chosen among other ecological EF tests since it is translated into cesses are crucial for many aspects of daily functioning, and thus, ex- several languages and can be performed as part of traditional neu- ecutive dysfunction has a significant impact on academic, vocational, ropsychological testing. emotional, social, and adaptive functioning (Bowie et al., 2006; Hunter and Sparrow, 2012; Jacques and Marcovitch, 2010; Jurado and 2. Methods and materials Rosselli, 2007).
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