عوامل پیش بینی شناخت در روان پریشی اپیزود اول

Purpose Cognitive deficits are common in the first episode of psychosis (FEP) and may begin much earlier. While some evidence suggests that the decline in cognition occurs over the untreated symptomatic period, including the prodromal phase, others point to these deficits being present even earlier. We aimed to investigate the differential effect of untreated symptomatic and pre-morbid phases on cognition in a large sample of FEP. Methods Two hundred and sixty eight FEP patients, admitted into a specialized early intervention service, were administered neuro-cognitive tests. The Circumstances of Onset and Relapse Schedule (CORS) was administered for measurement of duration of untreated psychosis (DUP), the duration of untreated illness (DUI) and demographic factors. The Pre-morbid Adjustment Scale (PAS) was used to measure different domains of pre-morbid adjustment. Seventy three healthy controls were also recruited for neuro-cognitive comparison. Results We observed no effect of DUP and a minimal effect of DUI on cognitive functioning in FEP. Instead, the early educational pre-morbid adjustment domain was most strongly associated with cognition and predicted both global cognitive and verbal memory outcome in FEP. Conclusion Our results suggest that symptoms associated with the symptomatic phase of a FEP do not influence cognitive functioning in FEP. Instead, cognitive deficits in FEP may predate illness onset and may indicate susceptibility to such illness.

Cognitive deficits are regarded as a fundamental feature of schizophrenia and related psychotic disorders (Milev et al., 2005). Compared to healthy controls, greatest impairments are reported in the domains of memory, attention, and executive function (Dickinson et al., 2004, Mesholam-Gately et al., 2009 and Holmén et al., 2010) and are linked to functional outcomes including independent living, occupational status, social relationships, and overall community behavior (Green and King, 1996, Green et al., 2000 and Leeson et al., 2009). As current treatments of these deficits are limited, they often persist throughout the course of illness (Harvey and Penn, 2010). Cognitive deficits are present at the time of presentation of treatment of the first episode of psychosis (FEP) (Mesholam-Gately et al., 2009) and to a lesser extent, prior to any psychotic symptoms, in both the pre-morbid as well as prodromal phases of illness (MacCabe, 2008, Woodberry et al., 2008 and Fusar-Poli et al., 2012). These deficits tend to remain stable from FEP to later stages of the illness with some possible decline in the later stages due to normal aging and medication effects (Zipursky et al., 2012). A recent meta-analysis reported medium deficits (ES = − 0.54) in the high risk stage (HR), likely representing the late prodromal phase, compared with larger deficits in FEP (ES = − 0.91) that remained relatively unchanged in the chronic phase (ES = − 0.96) (Mesholam-Gately et al., 2009). While the meta-analysis of cognition in the HR phase attempted to delineate the pre-morbid (asymptomatic) from the prodromal phase of illness by separating results of cognitive tests conducted during childhood from those in adolescence (Mesholam-Gately et al., 2009), this division is challenged by the inclusion of studies that did not specify participant age or used overlapping age ranges. Their conclusion of no deterioration in cognition between childhood and adolescence (MeshalomGately et al., 2009) is in contradiction to several studies reporting an increase in deficits over this transitional period (Watt and Lubensky, 1976, Jones et al., 1994, Bilder et al., 2006, Seidman et al., 2010 and MacCabe et al., 2013). What remains unclear is the extent to which the severity of cognitive deficits reported at the time of treatment of a FEP is accounted for by a decline that accompanies the onset of non-psychotic (prodromal phase) and/or psychotic symptoms or by cognitive deterioration that predates the onset of any symptoms, in early childhood or the early adolescence pre-morbid period. This may have some practical significance as any deterioration that accompanies onset of symptoms may be subject to intervention through early identification and interventions during the prodromal (such as, high risk mental states) and/or through early treatment of psychotic symptoms (Perkins et al., 2005). The link between the duration of untreated psychosis (DUP) and outcome is hypothesized to be mediated through a toxic effect on brain function (Wyatt, 1991), the latter likely to be represented by cognitive functions should hence reflect an association between duration of untreated psychotic symptoms and cognition. Similarly, the duration of untreated illness (DUI), which incorporates the prodromal as well as the untreated psychotic phase, may have a detrimental effect on long-term cognition but one that begins several years earlier with the start of non-specific symptoms such as depression and anxiety (McGlashan and Johannessen, 1996). While both hypotheses of the effect of DUP and DUI on cognition suggest the impact of either non-psychotic or psychotic symptoms on cognition, measures of pre-morbid adjustment, before the onset of any symptoms, imply a possible role for early neuro-developmental processes (MacCabe and Murray, 2004 and Demjaha et al., 2012), early environmental stressors (Wicks et al., 2005) and individual factors such as sex and substance abuse status (Rund et al., 2004). Among the studies investigating the effect of either DUP or DUI on cognitive functioning in psychosis, six have reported longer DUP to be associated with increased cognitive dysfunction (Scully et al., 1997, Amminger et al., 2002 and Joyce et al., 2005Lappin et al., 2007, Primavera et al., 2012 and Chang et al., 2012) while an equal number report no effect (Norman et al., 2001, Ho et al., 2003 and Addington et al., 2003Rund et al., 2007, Barnes et al., 2008 and Goldberg et al., 2009). None of the three studies that examined the effect of DUI on cognition found a relationship between the two (Scully et al., 1997, Hoff et al., 2000 and Keshavan et al., 2003), although not all used DUI as a primary independent measure. A recent meta-analysis (Bora and Murray, in press) found no deterioration in cognition between baseline and various lengths of follow-up (between 6 months and 5 years) for both those at Ultra High Risk (UHR) and those with an FEP suggesting that the extent of cognitive deficits seen in psychosis occur much earlier, prior to even the prodromal phase (Bora and Murray, in press). Studies that have investigated the association between pre-morbid adjustment and cognition have found either specific (e.g. Silverstein et al., 2002, Larsen et al., 2004, Addington and Addington, 2005 and Chang et al., 2013) or general cognitive deficits (Rabinowitz et al., 2006). Another recent study reported the degree of poverty of pre-morbid adjustment to be related to the severity, as opposed to the type, of cognitive deficits in FEP (Bechard-Evans et al., 2010). These discrepancies of the impact of symptomatic stages versus childhood and early adolescence factors on cognitive function in psychosis derived from multiple samples might be resolved by comparing the putative influence of these stages on cognitive functioning within the same group of FEP individuals. Therefore, our objective was to investigate cognitive deficits in the pre-morbid, prodromal, and untreated psychotic phases of illness and their potentially differential effect on cognitive functioning in a large sample of FEP through measures of pre-morbid adjustment, DUI, and DUP, while controlling for additional variables such as sex and substance abuse status that are known to influence cognitive functions. Given the equivocal results of previous research investigating the impact on cognition of the pre-morbid, prodromal, or untreated phases of the psychotic illness, no a-priori hypothesis is presented.