[Why do schizophrenic patients smoke?].
ABSTRACT Patients suffering from schizophrenia are known to show an increased prevalence of nicotine addiction. The aim of this paper is to elucidate the relationship between schizophrenia and (chronic) use of nicotine. Nicotine seems to improve cognitive functions critically affected in schizophrenia, in particular sustained attention, focused attention, working memory, short-term memory, and recognition memory. Furthermore, several studies using evoked potentials (P50 paradigm) and prepulse inhibition of the acoustic startle reflex suggest that deficient preattentive information processing, a core feature of schizophrenia illness, is improved following treatment with nicotine. Smoking can also improve extrapyramidal secondary effects of antipsychotic medication and it induces cytochrome P4501A2, an enzyme system involved in the metabolism of several antipsychotics. There is substantial evidence that nicotine could be used by patients with schizophrenia as a "self-medication" to improve deficits in attention, cognition, and information processing and to reduce side effects of antipsychotic medication. Possible pharmacotherapeutic approaches for the regulation of abnormal neurotransmission at nicotinic acetylcholine receptors are discussed.
- SourceAvailable from: Marc Wittmann[show abstract] [hide abstract]
ABSTRACT: Individuals are different 'chronotypes' with early 'larks' and late 'owls' forming the limits of a normal distribution in the population. We recently described that late chronotypes who suffer from a conflict between internal and external time ('social jetlag') suffer from more mental distress and are more likely to smoke than early chronotypes (Wittmann, Dinich, Merrow, and Roenneberg, 2006 . Social jetlag: mis-alignment of biological and social time. Chronobiology International, 23:497-509.). We performed a detailed analysis of the same database collected in 2002 comprising 134 daily smokers and 366 nonsmokers, scrutinizing the relationships between chronotype, smoking, and alcohol consumption as well as psychological well-being using a multiple mediation analysis. On average, smokers tend to be later chronotypes, report more sleep-associated psychosomatic symptoms, are more depressed, less balanced, and less vigilant. The mediation analysis suggests that only those late chronotypes who smoke and those who drink more suffer from increased psychological distress. We suggest that 'chronotype' is introduced as an additional factor in substance use, that is, when considering motives for smoking and drinking.Substance Use & Misuse 01/2010; 45(1-2):15-30. · 1.11 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Blockade of NMDA glutamate receptors with dizocilpine (MK-801) has been shown to cause substantial cognitive deficits and has been used to model symptoms of schizophrenia. Nicotine or nicotinic agonists, in contrast, may enhance cognitive or attentional functions and be of therapeutic potential in schizophrenia. Nicotinic-glutamatergic interactions, therefore, may have important implications in cognitive functions and antipsychotic treatments. Clozapine, a widely used antipsychotic drug, has been shown in some studies to be effective in ameliorating the cognitive deficits associated with schizophrenia. However, there is some evidence to suggest that clozapine similar to haloperidol may impair sustained attention in rats. In this study, we sought to determine whether chronic nicotine or dizocilpine may modify the effects of acute clozapine on attentional parameters and whether the behavioral effects would correlate with nicotinic or NMDA receptor densities in discrete brain regions. Adult female rats trained on an operant visual signal detection task were given 4 weeks of nicotine (5 mg/kg/day), dizocilpine (0.15 mg/kg/day), the same doses of both nicotine and dizocilpine as a mixture, or saline by osmotic minipump. While on chronic treatment, rats received acute injections of various doses of clozapine (0, 0.625, 1.25, 2.5 mg/kg, sc) 10 min prior to tests on attentional tasks. The pumps were removed on day 28 and 24 h later the animals were sacrificed for measurements of receptor densities in specific brain regions. The percent correct hit as a measure of sustained attention was significantly impaired by clozapine in a dose-related manner. Neither chronic nicotine nor dizocilpine affected this measure on their own or modified the effects of clozapine. Both nicotine and dizocilpine affected the receptor bindings in a region specific manner and their combination further modified the effects of each other in selective regions. Attentional performance was inversely correlated with alpha-bungarotoxin binding in the frontal cortex only. In conclusion, the data suggest attentional impairments with clozapine alone and no modification of this effect with nicotine or dizocilpine. Moreover, cortical low affinity nicotinic receptors may have a role in attentional functions.Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2008; 32(4):1030-40. · 3.55 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: People with schizophrenia suffer from a variety of symptoms that can be categorized as positive, negative and cognitive symptoms. Cognitive symptoms are not properly treated with antipsychotic medication and are the major cause of disability associated with the disorder. People with schizophrenia smoke more frequently and heavily than the general population. This observation in view of the well established role of nicotinic, cholinergic neurotransmission in cognition led to the hypothesis that people with schizophrenia may use nicotine as a self-medication to ameliorate cognitive symptoms associated with their disease. Furthermore genetic and post-mortem studies point to additional links between nicotinic cholinergic neurotransmission and schizophrenia. This article provides an insight in the possible relationship between schizophrenia and smoking behavior. We focus on the effects of nicotine on individual neurons as well as on neuronal networks. With respect to single neurons the immediate electrophysiological consequences of nicotinic stimulation and the more "metabotropic" effects related to intracellular signal transduction cascades that may lead to plastic changes in the neuron are discussed. With respect to the network level, three systems are discussed: cognition, reward and stress response. The effects of nicotine on cognition may be most pertinent to the problem of schizophrenia, but schizophrenics may also smoke to regulate mood and reduce stress. A better understanding of the molecular and cellular effects of nicotine and how they are related to the pathophysiology and symptomatology of schizophrenia may help to identify new targets for the pharmacotherapy of schizophrenia and of nicotine addiction in schizophrenia.Pharmacopsychiatry 09/2008; 41 Suppl 1:S51-9. · 2.11 Impact Factor