Effects of nicotine nasal spray on cognitive function in schizophrenia.

Department of Psychiatry, New York University Medical School, Hewlett, NY, USA.
Neuropsychopharmacology (Impact Factor: 7.83). 04/2006; 31(3):637-43. DOI: 10.1038/sj.npp.1300881
Source: PubMed

ABSTRACT Schizophrenics have among the highest rates of cigarette smoking. Some studies indicate that cigarette smoking or nicotine may ameliorate some of the cognitive or theoretically related neurophysiological deficits seen in schizophrenic patients. This study investigated the effects of nicotine nasal spray on measures of attention, verbal memory, and visual-spatial memory in schizophrenic patients who were chronic smokers, using a double-blind placebo-controlled pre-post experimental design. Compared to placebo, active nicotine spray significantly decreased reaction time on the Conner's CPT and improved scores on a measure purported to reflect spatial working memory on a dot task. There were trends for the increased number of hits and decreased number of errors in pre-post comparisons on the CPT task in the active nicotine session. There were no effects of active nicotine nasal spray on verbal memory. Our results suggest that nicotine may modestly enhance attention and spatial working memory in schizophrenic patients who are cigarette smokers and have been abstinent overnight.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia, a disabling mental disorder, is characterized by brain atrophy, especially in the superior temporal gyrus and the medial temporal lobe, which includes the hippocampus and the amygdala. The model that better explains brain atrophy includes a trigger and a predisposing condition. The trigger is exemplified by illicit drugs or environmental stressors that promote release of substances harmful to the neurons, such as glucocorticoids or noradrenalin. Predisposed patients would have one or more conditions that impair neuronal plasticity and neurogenesis. Evidence indicates that abnormal tissue plasminogen activator (tPA) activity is an important predisposing condition. tPA plays an important role in synaptic regulation and plasticity, and in neurogenesis, being crucial to the biology of memory, learning, and emotions. Several biochemical abnormalities seen in schizophrenics are related to decreased levels or impaired activity of tPA, including deficient dopamine transmission at D1 receptors in the prefrontal cortex, impaired cleavage of a precursor of brain-derived neurotrophic factor into its mature form (mature brain-derived neurotrophic factor), abnormal N-methyl-d-aspartate receptor-mediated signaling, reduced Akt phosphorylation, and abnormal activation of reelin. Clinical conditions related to schizophrenia, such as hyperhomocysteinemia, insulin resistance, and type 2 diabetes mellitus are characterized by a loss of tPA function or decreased tPA levels. This article reviews how low levels or abnormal function of tPA are related to the pathogenesis of schizophrenia.
    Seminars in Thrombosis and Hemostasis 10/2013; · 4.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive impairment associated with schizophrenia (CIAS) is a major and disabling symptom domain of the disease that is generally unresponsive to current pharmacotherapies. Critically important to the discovery of novel therapeutics for CIAS is the utilization of preclinical models with robust predictive validity. We investigated the predictive validity of MK-801-induced memory impairments in mouse inhibitory avoidance (MK-IA) as a preclinical model for CIAS by investigating compounds that have been tested in humans, including antipsychotics, sodium channel blocker mood stabilizers, and putative cognitive enhancers. The atypical antipsychotic clozapine, as well as risperidone and olanzapine (see Brown et al., 2013), had no effect on MK-801-induced memory impairments. For sodium channel blockers, carbamazepine significantly attenuated memory impairments induced by MK-801, whereas lamotrigine had no effect. Nicotine, donepezil, modafinil, and xanomeline all significantly attenuated MK-801-induced memory impairments, but the magnitude of effects and the dose-responses observed varied across compounds. Clinically, only acute administration of nicotine has demonstrated consistent positive effects on CIAS, while inconsistent results have been reported for lamotrigine, donepezil, and modafinil; atypical antipsychotics produce only moderate improvements at best. A positive clinical signal has been observed with xanomeline, but only in a small pilot trial. The results presented here suggest the MK-IA model lacks robust predictive validity for CIAS as the model is likely permissive and may indicate false positive signals for compounds and mechanisms that lack clear clinical efficacy for CIAS. Our findings also highlight the potential limitations and challenges of using NMDA receptor antagonists in rodents to model CIAS.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2013; · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Kognitive Defizite bilden eine klinisch relevante und für den Verlauf entscheidende Symptomgruppe der Schizophrenie. Die pharmakologische Behandlung der kognitiven Defizite stellt eine Herausforderung dar. Ziel dieses Artikels ist es, eine theoretisch fundierte und klinisch bedeutungsvolle Übersicht über die pharmakologischen Strategien der Behandlung kognitiver Defizite bei schizophrenen Psychosen zu geben. Die für die Behandlung schizophrener Psychosen zugelassenen Antipsychotika der 1. Generation sind hinsichtlich ihrer Wirkung auf die Kognition noch kontrovers. Die Antipsychotika der 2. Generation zeigen einen allenfalls geringen positiven Einfluss und sind denen der 1. Generation nicht nachweisbar überlegen. Vielversprechend erscheint der gezielte Einsatz von Präparaten, die kognitive Prozesse spezifisch beeinflussen können, so genannte kognitionsverbessernde Substanzen (,,cognition-enhancing drugs“).
    Der Nervenarzt 05/2010; 81(5). · 0.86 Impact Factor

Full-text (2 Sources)

Available from
Jun 10, 2014