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Cognitive Deficits in Schizophrenia

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Investigate the relationship between schizophrenia and cognitive ability. I am looking for one article about this topic as a place to begin my research and at least 25 sources.

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ARTICLE:

Cognitive deficits in schizophrenia: early course and treatment
Philip D. Harvey and Christopher R. Bowie

Department of Psychiatry, Box 1229, Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA

Abstract
Recent increases in interest in the importance of cognitive deficits in schizophrenia has increased awareness of these phenomena. Studies of the early course of schizophrenia have indicated that first episode patients clearly show these deficits, while some may even be present before the formal onset of symptoms. Furthermore, interest in treatment of these deficits has been increased by several reports indicating that newer antipsychotic medications enhance cognitive functioning in patients with schizophrenia, relative to treatment with older medications. This paper reviews data regarding the early course of cognitive deficits in schizophrenia, demonstrating that these deficits are clearly present at the time of the first episode. We also review the literature on cognitive enhancement with newer medications, considering the very latest publications in this area.

Cognitive deficits are the most stable and functionally relevant [1] features of schizophrenia. Impairments are widespread and severe [2], affecting attention, learning, memory, motor speed, verbal fluency, and executive functions to a magnitude corresponding to 1.5 or more S.D.s below normative standards [3]. While negative and positive symptoms tend to fluctuate during the course of the illness, cognitive deficits appear relatively stable over time across changes in clinical state [4]. Thus, they appear, like functional deficits, to be quite stable over time in patients with an established course of illness.

There is considerable evidence to indicate that cognitive deficits are not only present before the onset of the first episode of illness, but that they may also be markers of vulnerability to the illness. In individuals who are vulnerable to schizophrenia by virtue of having a first degree relative with the illness, notable cognitive deficits are seen. For example, impairments in attention [5 and 6], memory [7], and motor skills [7] are detectable in these individuals. Some data indicate that greater severity of attentional impairment in adolescence identifies those children of a schizophrenic parent who are most likely to develop schizophrenia [8]. These data suggest that the cognitive deficits seen in schizophrenia during the premorbid phase, particularly those in vulnerable individuals have direct implications for vulnerability to schizophrenia.
This impression has been confirmed by several other archival studies of individuals who were examined prior to the onset of their schizophrenia with a variety of different cognitive measures. Several studies have indicated that reductions in intellectual performance are seen in individuals who later develop schizophrenia [9 and 10]. These deficits are paralleled with data collected even earlier in life, indicating that academic deficits are common in individuals who develop schizophrenia as adults. For instance, academic deficits can be detected as early as the second grade in school [11 and 12]. These premorbid cognitive and academic differences are also noted when monozygotic co-twins who are discordant for schizophrenia are compared [13].

A limitation of these data is that the premorbid differences in cognitive functioning seen between individuals who develop schizophrenia and those who do not are not sufficient to be considered as diagnostic indicators. The effect sizes seen for the differences are rarely as large as a full standard deviation of difference and often they are much smaller. There is also considerable overlap in the distributions, with many individuals with essentially no liability for lifetime psychopathology performing in the same general range as those who eventually develop schizophrenia. As a result, the presence of cognitive impairment in an adolescent, even if they are known to have a family history of schizophrenia, does not allow for the determination as to whether they are likely to develop schizophrenia later.

This is not necessarily a fatal problem with these studies. Similarly, cognitive impairments do not allow for the reliable differential diagnosis of schizophrenia as compared to other neuropsychiatric conditions. For example, cognitive deficits do not reliably discriminate older individuals with schizophrenia and Alzheimer's disease [14 and 15]. Accurate prediction of those individuals who later develop schizophrenia is enhanced considerably when social deficits, academic problems, and cognitive impairments are combined together into the prediction equation.

One of the major questions in schizophrenia is whether there is actually a decline in cognitive and intellectual functions at the time of the onset of psychosis. Some data have suggested that assessments performed before and after the onset of schizophrenia are essentially no different [16] but that they are lower in general than their first-degree relatives [17]. Other data indicate that the same cognitive assessments repeated after illness develops detect reductions in performance [18]. Much of the data suggesting that there is intellectual decline has come from studies where premorbid intellectual functioning is estimated on the basis of achievement tests [19]. Estimated IQ's are not guaranteed to be equivalent IQ scores obtained in a truly prospective manner.

One of the problems in this area is common to archival studies in general: the type of data collected may not be the most relevant to address the issue at hand. The specific aspects of cognitive functioning in schizophrenia that are directly relevant to functional outcome are not common tests performed on individuals who are healthy. Thus, the results of such tests are not likely to be commonly found in the types of records examined in archival studies. A possible exception are the data presented in the Davidson et al. [10] study and related publications, where relatively comprehensive cognitive and aptitude testing was performed as a part of the induction examinations for the Israeli army.

While longitudinal follow-up data are not widely available, it is generally accepted that cognitive deficits in the premorbid phase of schizophrenia are similar in pattern, but not as severe as the cognitive deficits observed after the emergence of psychotic symptoms. Cognitive impairments are common and severe by the time patients experience their first episode of psychosis, even before neuroleptic medication, with average performance approaching the level of chronic patients [20 and 21]. Superimposed on a pattern of generalized cognitive deficits similar to chronic patients, first episode patients evidence specific deficits in memory and executive functions [22]. These deficits are more severe than those seen in patients with first episode affective psychoses [23]. The worsening of cognitive functions from the premorbid phase to the first episode supports the notion of a progressive decline in cognition. However, study of the course of cognitive deficits immediately after first episode has led to the conclusion that there is actually considerable stability at that time.

For instance, several longitudinal follow-up studies of first episode patients have found no change to modest improvement in most cognitive functions [24, 25 and 26]. Thus, either the first episode of schizophrenia marks an initial inflection point in the early downward course of cognitive functions or the treatments offered for schizophrenia arrest that downward course. One line of thinking that is consistent with the second interpretation is that of the influences of duration of untreated psychosis (DUP). This is based on the historical finding that patients who received treatment with conventional antipsychotic medications early in their course of illness had a better long-term course of illness than those whose DUP was longer [27]. Several studies of first episode patients supported the idea that longer DUP was associated with more adverse short-term outcome [28 and 29]. Recently, however, there have several failures to replicate this finding [30 and 31] suggesting that the relationship between length of psychosis before treatment and short and intermediate-term outcome is quite complex. Thus, it cannot be expected that early initiation of antipsychotic treatment offers a definitive beneficial effect. Since this is a particularly important issue, we will address this issue in the context of the importance of early treatment of cognitive deficits and the resulting implications for the prevention of schizophrenia.

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