Effects of Nicotine on Cognitive Deficits in Schizophrenia

Abstract

Several lines of evidence suggest a pathophysiological role for nicotinic receptors in schizophrenia. Activation by nicotine alters physiological dysfunctions, such as eye movement and sensory gating abnormalities, but effects on neuropsychological performance are just beginning to be investigated. Nicotine-induced desensitization and the well-known tachyphylaxis of nicotinic receptors may confound such efforts. In all, 20 schizophrenics, 10 smokers, and 10 nonsmokers were assessed following the administration of nicotine gum and placebo gum. The Repeatable Battery for the Assessment of Neuropsychological Status was administered. Nicotine affected only the Attention Index; there were no effects on learning and memory, language, or visuospatial/constructional abilities. Attentional function was increased in nonsmokers, but decreased in nicotine-abstinent smokers after nicotine administration. The effects of nicotine in schizophrenia do not extend to all areas of cognition. Effects on attention may be severely limited by tachyphylaxis, such that decremented performance occurs in smokers, while modest effects may be achieved in nonsmokers.

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

“…There is increasing evidence that nAChR stimulation has beneficial effects on cognitive function in schizophrenia, possibly via presynaptic modulation of dopamine and/or glutamate release (McGehee et al, 1995;George et al, 2000;Picciotto et al, 2000;Wonnacott et al, 2000). The administration of both short-and long-acting preparations of nicotine to individuals with schizophrenia has been associated with improved neuropsychological performance (Levin et al, 1996b;Depatie et al, 2002;Smith et al, 2002Smith et al, , 2006Harris et al, 2004;Jacobsen et al, 2004;Myers et al, 2004). Acute administration of the selective a7nAChR partial agonist, DMXB-A, improved P50 gating compared with placebo (Olincy et al, 2006) and administration of the nAChR antagonist, mecamylamine, blocked smoking-associated improvements in performance on attentional and visuospatial working memory (VSWM), implying that nAChR activation mediates smoking-related cognitive enhancement (Sacco et al, 2005).…”

“…However, many studies investigating the effects of nicotinic stimulation in schizophrenia have been conducted in smokers who have undergone a brief period of abstinence from smoking prior to testing of nicotine effects. Under such circumstances, cognitive benefits observed following the nicotine administration may be confounded by reversal of nicotine withdrawal symptoms or limited by tachyphylaxis (Harris et al, 2004). We, therefore, performed the following study to investigate the acute effects of nicotine on cognition in nonsmokers with schizophrenia and healthy controls.…”

“…We, therefore, performed the following study to investigate the acute effects of nicotine on cognition in nonsmokers with schizophrenia and healthy controls. We selected a measure of attention as our primary outcome as the nAChR system is thought to play an integral role in the regulation of attentional processes (Mansvelder et al, 2006) and several previous studies have reported an improvement in this cognitive domain following nicotine administration in individuals with schizophrenia (Depatie et al, 2002;Harris et al, 2004;Sacco et al, 2005;Smith et al, 2006). Our primary hypothesis was that nicotine would enhance attention in nonsmokers with schizophrenia and controls; and the secondary hypothesis was that nicotine-associated improvements in cognition would be greater in the schizophrenia group compared with controls.…”

Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function

“…Attentional improvement by nicotinic agents may be a key therapeutic effect for these psychiatric disorders [83,84]. It has been demonstrated that smoking withdrawal induced deficits in both attentional performance and spatial working memory in patients with schizophrenia [85].…”

“…In a complementary fashion, nicotinic blockade caused significant deficits in the N-back task [91].. Nicotine nasal spray has been shown to improve spatial organization and also improve memory in people with schizophrenia [92,93]. Nicotine also improves eye tracking, memory and attentional function in schizophrenia [84,85,88,92]. Nicotine skin patch treatment in healthy volunteers significantly improved the speed of pre-attentive sensory processing as indexed by mismatch negativity to auditory stimuli in an oddball paradigm [94] Specific nicotinic receptors may be more promising for the improving aspects of cognition in people with schizophrenia .…”