Neurocognitive Expression of Hypofrontality in Long Term Schizophrenia

Abstract

Despite over a century of studies on schizophrenia, its pathogenesis still remains unexplained. In particular, cognitive dysfunctions, related to a decrease of prefrontal cortex activity in the human brain represent one of the main symptoms of schizophrenia. The cognitive dysfunctions usually precede, by a few years, the first acute episode of the disease. These dysfunctions are present in approximately 70% of persons suffering from schizophrenia, and can be maintained at a stable level over the rest of their lifetime (Rund et al., 2006). For instance, majority of patients enrolled in the CATIE study suffered from the cognitive disorders (Lieberman et al., 2005a). According to Javitt (2010), the cognitive deficits are the key symptoms of schizophrenia, which usually precede an onset of some other symptoms of this disease. Due to that, the cognitive disorders can represent the leading concept among hypotheses, related to etiology of schizophrenia. The main component of these disorders is the deterioration of attention concentration and operative memory deficits, including the difficulty of holding some elements in short-term memory (Goldman-Rakic, 1999) that in turn translates into some cognitive dysfunctions. These disorders include also memory, learning abilities, and executive functions (Meltzer & McGurk, 2004). The cognitive dysfunctions related to hypofrontality consist of deterioration of the activity of prefrontal brain cortex (Carter et al., 1998). In majority of patients, the cognitive deficits begin prior to their first disease episode, in the prodromal stage (Fuller et al., 2002). Individuals with prodromal schizophrenia symptoms often present deficits, ranging in intensity from almost normal conditions to the ones, resembling mental status of patients with the first episode of their disease (Lencz et al., 2006). In this aspect, neurocognitive disorders can be considered as the initial schizophrenia symptoms (Javitt, 2010). Due to these reasons, the cognitive disorders appear to be closely connected with the etiology of schizophrenia (Kantrowitz & Javitt, 2010b). In schizophrenia, the cognitive dysfunctions and hypofrontality are associated with hypofunction of NMDA receptors (NMDA-R) (Marek et al., 2010), and according to Carlsson (2006), an abnormal function of NMDA-R is the main cause of schizophrenia. These cognitive disorders, mostly in form of concentration deterioration, and deficits of operative memory are results of prefrontal cortex dysfunctions, which are related to the