Response inhibition and cognitive flexibility in schizophrenia with and without comorbid substance use disorder

Frontostriatal Involvement in Task Switching Depends on Genetic Differences in D2 Receptor Density

“…In particular, high DRD2 density is a major component in the pathophysiology of schizophrenia (Wong et al, 1986;Abi-Dargham et al, 2000). While many studies show impaired cognitive flexibility in schizophrenic patients (Rodríguez-Sánchez et al, 2005;Thoma et al, 2007), only recently the link between high DRD2 density and cognitive inflexibility was established: a genetic mutation study showed that the overexpression of striatal D2 receptors in transgenic mice was directly related to reversal learning deficits (Kellendonk et al, 2006).…”

“…Most prominently, increased striatal DRD2 density is characteristic for schizophrenia (Wong et al, 1986;Abi-Dargham et al, 2000), which is associated with impaired cognitive flexibility (Rodríguez-Sánchez et al, 2005;Thoma et al, 2007). Increased DRD2 availability is further associated with changes in prefrontal dopamine levels and cognitive inflexibility in transgenic mice (Kellendonk et al, 2006), suggesting that striatal DRD2 density might also modulate switching performance in human prefrontal cortex.…”

The Role of Executive Control in Human Drug Addiction

“…Other populations that are at-risk of developing drug dependence are those children with diagnoses of oppositional defiant disorder, conduct disorder, and attention deficit hyperactivity disorder (Myers et al 1995;Zoccolillo et al 1997;Riggs 1998;Whitmore et al 2000;Finn et al 2005), as well as young people with psychiatric disorders such as schizophrenia and bipolar disorder (Dixon 1999;Batel 2000;Crome 2000;Soyka 2000;Chambers et al 2001;Altamura 2007;Thoma et al 2007). These disorders are consistently associated with impairments in executive control as well as disruptions to frontal brain circuitry, highlighting the role that executive deficits play in increasing risk for drug addiction.…”

Opposite relationships between cannabis use and neurocognitive functioning in bipolar disorder and schizophrenia

“…Carey et al (2003) reported that dual-diagnosis patients with schizophrenia or bipolar disorder performed better on non-verbal neuropsychological tests than those who never abused. Studies of general substance use in schizophrenia spectrum disorder patients showed diverging results (Joyal et al 2003 ;Herman, 2004 ;Thoma et al 2007 ;Wobrock et al 2007 ;Potvin et al 2008 ;van Os et al 2009). In the only intervention study, administration of D 9 -tetrahydrocannabinol (THC) to patients with schizophrenia was followed by a temporary reduction in verbal learning and memory (D'Souza et al 2005).…”