خط سیر تکاملی اختلال شناختی در اختلال دو قطبی: مقایسه با اسکیزوفرنی

Both schizophrenia and bipolar disorder (BP) are associated with neurocognitive deficits. However, it has been suggested that schizophrenia, but not BP, is characterised by premorbid cognitive impairments and neurodevelopmental abnormalities. In this paper, studies investigating neurocognitive deficits in premorbid, high-risk and first-episode BP were reviewed and these findings were compared with outcome of studies in schizophrenia. Available evidence suggests that cognitive deficits are evident in first-episode BP and such deficits can be evident even years before the onset of the illness in some patients. Trajectory of cognitive deficits from childhood to adulthood can be very similar in schizophrenia and many patients with BP. Developmental lag in acquisition of cognitive skills is a risk factor for both disorders. However, unlike schizophrenia, not only impaired cognition but also supranormal premorbid cognitive/scholastic performance predict BP. Neurodevelopmental cognitive impairment is evident in some but not all patients with BP. A model suggesting that only BP patients who share common genetic risk factors with schizophrenia have premorbid neurodevelopmental cognitive deficits is proposed. In this model, combination of absence of neurodevelopmental abnormalities and BP-related temperamental characteristics explains the relationship between supranormal cognition and risk for BP.

Cognitive dysfunction is a common and robust feature of schizophrenia (Gold and Harvey, 1993, Heinrichs and Zakzanis, 1998 and Bora et al., 2010a). Bipolar disorder is also associated with cognitive deficits in a number of domains including executive functions, attention and memory that persists in remission (Bora et al., 2009a). The pattern of these cognitive deficits overlaps in schizophrenia and BP, but cognitive dysfunction is less severe in BP (Bora et al., 2009b and Krabbendam et al., 2005). It is argued that cognitive deficits in BP and schizophrenia might have very different trajectories. In schizophrenia, there is a consensus that neurodevelopmental factors play an important role in cognitive deficits. A number of studies have provided evidence indicating that cognitive and intellectual deficits are evident early in neurodevelopment, including childhood, well before the onset of psychosis (Fuller et al., 2002, Kahn and Keefe, 2013 and Reichenberg et al., 2010). It seems that cognitive development is abnormal in children and adolescents who develop adult schizophrenia. In addition to cognitive deficits, findings such as increased prevalence of neurological soft signs, childhood motor and language impairments, and prenatal and obstetric complications are among evidence supporting neurodevelopmental abnormality in schizophrenia (Murray and Lewis, 1987: Weinberger, 1986). Some authors also suggested that premorbid cognitive deficits in schizophrenia are not only related to problems in development of cognitive abilities but also to loss of acquired cognitive abilities before or around the onset of first-episode (Kahn and Keefe, 2013). In contrast to findings in schizophrenia, a number of studies have suggested normal, at times superior, cognitive abilities and school achievement in children and adolescents who develop adult BP (Kumar and Frangou, 2010). There is also good evidence suggesting a relationship between BP and creativity in adulthood (Kyaga et al., 2011). Therefore, it has been suggested that developmental cognitive abnormalities might be specific to schizophrenia (Kahn and Keefe, 2013 and Murray et al., 2004). Patients with BP only develop cognitive deficits during the course of illness; whereas in schizophrenia cognition is impaired before the onset of the illness and at first-episode. On the other hand, another evidence suggests that abnormalities in neurodevelopment can play a role not only in schizophrenia but also in BP. A number of potential common susceptibility genes for schizophrenia and BP have a role in neurodevelopment (Craddock and Owen, 2010). There is also evidence suggesting that neurological soft signs might be more common in BP than healthy controls (Zhao et al., 2013). Some studies also suggested a link between prenatal and perinatal abnormalities and BP. A recent study showed a four-fold increase in risk for BP in adult offspring of mothers who had gestational influenza (Parboosing et al., 2013). Some evidence suggests that cognitive impairment in BP can be associated with abnormalities in genes that have role in brain development (Tabarés-Seisdedos et al., 2008). Further studies have reported cognitive abnormalities in first-episode of BP and unaffected healthy relatives of BP patients (Bora et al., 2009a and Torres et al., 2010). It is also important to note that longitudinal studies in chronic patients with BP and few available studies in first-episode BP (Bombin et al., 2013 and Torres et al., 2014) have not so far supported evidence for progressive cognitive decline in BP. These findings are rather similar to outcome of longitudinal studies in schizophrenia (Bora and Murray, 2013 and Szöke et al., 2008) which suggest that neurodevelopmental factors might play an important role in major psychoses. Therefore, it is important to revisit the question of specificity of neurodevelopmental cognitive deficits to schizophrenia and offer an explanation to reconcile the seemingly contradicting findings in BP. The aim of the current paper is to review the studies investigating cognitive deficits in premorbid and early BP, compare these findings to schizophrenia and explore the relationship between premorbid cognitive functioning and BP risk. In the first part of the paper, neurocognitive studies in first-episode and high-risk samples were reviewed. In the second part of the paper, studies investigating premorbid cognitive deficits in BP and schizophrenia and course of these deficits were explored. In the final part, a proposal to explain the dual nature of relationship between cognitive/scholastic performance and risk for BP is introduced.

The relationship between premorbid cognitive impairment and BP, as defined in current classification systems, is a complex one. On the one hand, neurodevelopmental abnormalities partly separate BP from schizophrenia. Many BP patients have no shared neurodevelopmental abnormality with schizophrenia. These patients have no premorbid cognitive deficits and they can function at supranormal level more often than healthy controls due to the positive effects of temperamental characteristics seen in BP. On the other hand, premorbid cognitive impairment is not specific to schizophrenia. Available evidence suggests that developmental trajectories of cognitive deficits in many other BP patients are similar to schizophrenia. Current evidence also suggests that premorbid cognitive deficits in these patients are the result of problems in acquisition of cognitive abilities rather than cognitive decline. The model proposed in this paper suggests that developmental lag in acquisition of cognitive abilities is not only a robust risk factor for schizophrenia but also for “mixed psychoses” that are diagnosed as BP and schizoaffective disorder in current diagnostic systems. These BP patients share genetic risk factors with schizophrenia and are more likely to present with schizophreniform psychotic symptoms in addition to mood symptoms. A combination of the absence of neurodevelopmental abnormalities and positive temperamental characteristics increases the likelihood of supranormal scholar, cognitive and artistic skill in other patients with BP.