دانلود مقاله ISI انگلیسی شماره 30264
ترجمه فارسی عنوان مقاله

عوامل افزایش شناختی در اسکیزوفرنی و اختلال دو قطبی

عنوان انگلیسی
Cognitive enhancing agents in schizophrenia and bipolar disorder
کد مقاله سال انتشار تعداد صفحات مقاله انگلیسی
30264 2015 صفحه PDF
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : European Neuropsychopharmacology, Available online 18 April 2015

ترجمه کلمات کلیدی
اسکیزوفرنی - اختلال دوقطبی - شناخت - اختلال شناختی - فارماکولوژی - توسعه مواد مخدر -
کلمات کلیدی انگلیسی
Schizophrenia, Bipolar disorder,Cognition, Cognitive impairment, Pharmacology,Drug development,
پیش نمایش مقاله
پیش نمایش مقاله  عوامل افزایش شناختی در اسکیزوفرنی و اختلال دو قطبی

چکیده انگلیسی

Cognitive dysfunction is a core feature of schizophrenia and is also present in bipolar disorder (BD). Whereas decreased intelligence precedes the onset of psychosis and remains relatively stable thereafter; high intelligence is a risk factor for bipolar illness but cognitive function decreases after onset of symptoms. While in schizophrenia, many studies have been conducted on the development of cognitive enhancing agents, in BD such studies are almost non-existent. This review focuses on the pharmacological agents with putative effects on cognition in both schizophrenia and bipolar illness; specifically agents targeting the dopaminergic, cholinergic and glutamatergic neurotransmitter pathways in schizophrenia and the cognitive effects of lithium, anticonvulsants and antipsychotics in BD. In the final analysis we conclude that cognitive enhancing agents have not yet been produced convincingly for schizophrenia and have hardly been studied in BD. Importantly, studies should focus on other phases of the illness. To be able to treat cognitive deficits effectively in schizophrenia, patients in the very early stages of the illness, or even before – in the ultra-high risk stages – should be targeted. In contrast, cognitive deficits occur later in BD, and therefore drugs should be tested in BD after the onset of illness. Hopefully, we will then find effective drugs for the incapacitating effects of cognitive deficits in these patients.

مقدمه انگلیسی

Cognitive dysfunction is a core feature of schizophrenia; in fact schizophrenia may arguably be considered a cognitive disorder (Kahn and Keefe 2013). Indeed, cognitive decline precedes the onset of psychosis by almost a decade (Maccabe et al., 2008, Elvevag and Goldberg, 2000, van Oel et al., 2002 and Reichenberg et al., 2010); after the onset of psychosis cognitive deficits remain present and may even progress further (Hedman et al. 2013). Cognitive dysfunction has a clear detrimental influence on socio-vocational outcome in schizophrenia patients (Green, 1996 and Green et al., 2000), making cognitive enhancement an important target for treatment. Bipolar disorder (BD), classified as mood disorder, has several clinical characteristics with schizophrenia in common and both disorders partly share a genetic background (Purcell et al., 2009 and Owen and Craddock, 2009). However, in stark contrast with schizophrenia, premorbid BD patients demonstrate normal or even higher premorbid cognitive functioning compared to controls (Zammit et al., 2004, Gale et al., 2013 and Maccabe et al., 2010). Yet, cognitive dysfunction does occur after the onset of illness in many BD patients (Trotta et al. 2014). Accumulating evidence suggests that cognitive dysfunction is also found in euthymic BD patients (Martinez-Aran et al., 2004b, McIntosh et al., 2005 and Toulopoulou et al., 2006). The reason for the apparent cognitive decline in BD remains elusive. An extensive number of agents has been examined in schizophrenia patients targeting several neurotransmitter pathways associated with cognitive function. To date, cognitive enhancing agents have hardly been studied in BD; research focuses on the indefinite cognitive effects of mood-stabilizing agents in these patients. In this review, we will focus on two topics: 1. The cognitive effects of pharmacological agents targeting the dopaminergic, cholinergic and glutamatergic neurotransmitter pathways with a concise overview of the cognitive effects of other agents in schizophrenia. 2. The effects of lithium, anticonvulsants and antipsychotics, on cognitive function in BD. In the context of this review the term cognitive function means any measure of cognitive performance such as memory, attention, acquisition of knowledge, processing speed, reasoning and executive function (Kahn and Keefe 2013).

نتیجه گیری انگلیسی

Despite extensive efforts on the development of cognitive enhancing drugs, to date no putative agents with such properties have been produced for schizophrenia. Antipsychotics appear to mildly improve cognitive function in schizophrenia patients (more in first episode than in chronic patients), but these agents do not improve cognitive function to any meaningful degree. Also, cognitive enhancing effects by dopamine agonists and glutamatergic drugs have been reported. However, results are inconclusive and at best suggest an improvement in cognitive subdomains. Cholinergic agents, in particular galantamine and nicotine, appear to have the most promising cognitive enhancing effects in schizophrenia patients. Whereas in schizophrenia the goal of research is to develop new putative cognitive enhancing agents, BD research still focuses on the cognitive effects of current available mood-stabilizers and antipsychotics. Cognitive enhancing agents in BD have not been proposed so far. There are some indications that lithium may act as a cognitive enhancing agent in a subgroup of BD patients with an excellent lithium response. However, the research methodology in BD so far is flawed using, as it does, mostly cross-sectional designs. Clearly, prospective randomized (placebo-)controlled trials are necessary to investigate the cognitive effects of medication in BD. In fact, the study of cognitive dysfunction (and its treatment) in BD is severely underdeveloped despite the relevance of cognitive dysfunction in the later stage of the illness. In schizophrenia, the majority of clinical trials testing the efficacy of putative cognitive enhancing agents have focused on chronic patients. As cognitive decline precedes the first psychotic episode by many years, these studies may have barked up the wrong tree. Therefore, the focus of research should be on patients in an earlier phase of the illness, preferably when the first cognitive deficits appear. Since it is difficult to identify the first cognitive problems in the general population, targeting a population with increased vulnerability for schizophrenia may be more appropriate. Monitoring an ultrahigh risk population provides the opportunity to administer cognitive enhancing agents if the first cognitive deficits appear. In contrast, studies examining putative cognitive enhancing agents in BD patients should focus on the illness stage that occurs after the onset of (mood)symptoms, since cognitive function in BD decrease after the onset of illness. Hopefully, these recommendations will accelerate the development of cognitive-enhancing drugs for schizophrenia and bipolar disorder patients. They are sorely needed.