مدت زمان روان پریشی درمان نشده و عملکرد شناختی

Background Studies examining the influence of duration of untreated psychosis (DUP) or duration of untreated illness (DUI) on cognition vary with regard to results and methods. This study is the first in this field to include an at risk mental state with later transition to psychosis (ARMS-T) sample and to analyse how the DUI relates to their cognitive functioning. Because methodological operationalization of cognitive functioning in previous studies is highly heterogeneous, we aimed to compare different approaches. Method 60 first episode psychosis (FEP) patients and 24 ARMS-T patients were examined. Associations between DUP, DUI and neurocognitive performance were tested by three different operationalizations of cognition: as the raw outcome measure of different neuropsychological tests, as outcome scores which were normed on a sample of 75 healthy participants, and as the deterioration index (DI). Results There were no significant correlations between DUP or DUI and outcome of neuropsychological tests in both normed and raw scores. When adjusted for covariates, DUP and DUI also did not significantly predict any cognitive performance. There was no significant relationship between DUP or DUI and the DI index. However, longer DUP and DUI were significantly associated with stronger negative symptoms. Conclusions This study could not confirm an association between duration of untreated psychosis or duration of untreated illness and neurocognitive performance in the ARMS-T and FEP samples. This could be because schizophrenic psychoses are neurodevelopmental disorders in which most cognitive deficits exist long before the onset of psychiatric symptoms.

Duration of untreated psychosis (DUP) is defined as the time from appearance of the first psychotic symptom to initiation of adequate neuroleptic treatment (Marshall et al., 2005). Shorter DUP is associated with better clinical outcome (Marshall et al., 2005) and greater response to antipsychotic treatment (Perkins et al., 2005). The specific association between DUP and cognitive deficits at treatment initiation has been analysed in several studies and gained importance based on the hypothesis that psychosis might have a “toxic effect” on the brain (Wyatt, 1991). However, among 18 studies which have so far examined this association, only 6 found a positive association whereas 13 did not (Supplementary Table 1). The studies vary with regard to methods and operationalization of DUP, which makes these data difficult to interpret. Some of these studies also considered the relationship of cognitive deficits with duration of untreated illness (DUI), which is usually defined as the DUP plus any period of prodromal symptoms (e.g. Barnes et al., 2000). Most of the existing studies analysed the association between DUP and cognitive functioning by relating DUP to different neuropsychological tests and IQ measures at the time of treatment initiation (e.g. Goldberg et al., 2009). However, Amminger et al. (2002b) argued that only the difference to a patient's premorbid abilities would provide a meaningful measure for deterioration. Consequently, they made use of the deterioration index (DI; Bilder et al., 1985), assessing the discrepancy between “hold” and “non-hold” cognitive functions. In accordance with the above hypothesis, Amminger et al. (2002a) found that DUP was positively associated with DI, but not with morbid cognitive functioning, which was replicated by Gaynor et al. (2009). Because methodological operationalization of cognitive functioning in studies examining the relationship between DUP and cognitive decline is highly heterogeneous, we aimed to compare different approaches in order to detect whether differences in methodological approaches could have led to inconsistencies between earlier studies. Specifically, we analysed the relationship between DUP, DUI and cognitive deterioration in three different ways: first, we operationalized cognitive functioning as raw outcome measure of different neuropsychological tests as done in most similar studies. Second, we analysed the relationship between DUP, DUI, and cognitive deficits using neuropsychological outcome scores normed on a sample of 75 healthy participants with the same socio-demographic characteristics. Thirdly, deterioration was assessed by the DI in a similar way as in Amminger et al. (2002a) and Gaynor et al. (2009). Of the studies listed in Supplementary Table 1, only four have also looked at the interrelationship between DUI (other than DUP) and cognition. None of them found significant correlations. A difference between the effect of DUP versus DUI on cognitive performance might be expected in the way that cognitive performance could be affected more strongly by DUP than by DUI because later stages of the disease process (i.e. stages with psychotic symptoms) are likely to be more toxic to the brain than earlier stages. This study is the first to include 24 at risk mental state (ARMS) individuals with later transition to psychosis (ARMS-T) and to examine how the DUI relates to their cognitive functioning at presentation to our clinic. The inclusion of an ARMS sample with only unspecific prodromal signs but later transition to psychosis can help to clarify the influence of first psychiatric symptoms on cognition, eventually detecting that untreated first psychiatric symptoms are associated with cognition before the outbreak of psychosis. However, based on previous studies with first episode psychosis (FEP) patients reporting no relationship between DUI and cognition (e.g. Barnes et al., 2000 and Norman et al., 2001), we expected no relationship between DUI and cognitive functioning in this patient group, which could mean that cognitive deficits occur prior to the onset of psychiatric symptoms.