Шизофрения и курение

The self-medication hypothesis of smoking in schizophrenia

There is a discrepancy in the literature, with numerous animal studies suggesting that nicotine should help negative symptoms but scarce clinical data suggesting that this may be true in those with schizophrenia (Hughes, 2000). Two main sub-hypotheses are usually included in the self-medication hypothesis: smoking reduces the side-effects of antipsychotics; and nicotine may improve schizophrenic symptoms, particularly the negative, cognitive and/or depressive symptoms (Taiminen et al, 1998).

Two mechanisms have been implicated in the reduction of antipsychotic side-effects: a release of dopamine resulting from the administration of nicotine, a notion supported by both acute administration of nicotine in animal models (Drew et al, 2000) and in vivo human studies (Salokangas et al, 2000); and a decrease in antipsychotic blood levels through enzymatic induction. Individuals with schizophrenia who smoke tend to receive consistently higher doses of antipsychotics than non-smokers (Ziedonis et al, 1994; de Leon et al,1995, 2002a). The inductive effect of smoking in antipsychotic metabolism therefore is inadvertently corrected by psychiatrists, because smokers tend to be treated with higher daily doses of antipsychotics than non-smokers. When compared with others with severe mental illness in three epidemiological studies in psychiatric hospitals, the effect of antipsychotic medication did not explain the association between schizophrenia and smoking (de Leon et al,1995, 2002a; Llerena et al, 2003). Some cross-sectional studies have suggested that smoking reduces antipsychotic side-effects and others have not (Dalack et al, 1998); yet all of these studies are hampered by the lack of control for confounding factors. Longitudinal studies with small samples suggest that, when compared with atypical antipsychotics, typical antipsychotics are associated with increased smoking in some individuals (McEvoy et al, 1995) and with a greater difficulty for quitting smoking (Georgeet al, 2000). Anticholinergic medication was not associated significantly with smoking in this or in previous studies (de Leon et al, 1995, 2002a, b).

In spite of the hypothesis from animal studies (Drew et al, 2000), very limited clinical data support an association between smoking and a reduction in negative symptoms (Dalack et al, 1998). Data indicating that nicotine may improve sensory gating abnormalities and smooth pursuit eye movements in schizophrenia or cognitive abnormalities induced by antipsychotics are somewhat stronger. Nicotine may have antidepressant qualities in individuals with depression (Salin-Pascual et al, 1996), but this is not well established in those with schizophrenia.

The literature appears to suggest that those with severe forms of schizophrenia may smoke more frequently, and more heavily, than those with less severe forms (Lohr & Flynn, 1992). The possible beneficial effect of nicotine (and smoking) on schizophrenic symptoms and antipsychotic side-effects may be obscured by this association between smoking and severe forms of schizophrenia. In summary, a critical reading of the literature lends very limited support to the self-medication hypothesis, but this effect may be obscured by the association between severe forms of schizophrenia and heavy smoking.

Nicotine dependence and symptoms in schizophrenia 

Перспективные стратегии лечения когнитивной симптоматики шизофрении

A randomized, double-blind, placebo-controlled study demonstrated that members of a sarcosine (2 g/day) group showed greater reductions in their Positive and Negative Syndrome Scale (PANSS) total scores than members of a placebo group or D-serine (2 g/day) group, suggesting that sarcosine is superior to D-serine in that benefits both patients with long-term stable disease and also acutely ill persons with schizophrenia .

Furthermore, a randomized, double-blind study reported that sarcosine (2 g/day) alone was effective in the treatment of acutely symptomatic drugfree patients with schizophrenia.

Nonetheless, all these findings suggest that GlyT-1 inhibition could be a novel pharmacotherapeutic target for enhancing cognitive dysfunction in schizophrenia and several clinical trials are underway with very promising results.

Gaining a better understanding of the role of GlyT-1 in the treatment of cognition in schizophrenia is expected to provide new perspectives for treating this disorder. The pharmacological modulation of glycine modulatory sites on NMDA receptors by GlyT-1 inhibitors could be beneficial in the treatment of the cognitive deficits and psychosis associated with schizophrenia and other psychiatric conditions.

Galantamine, which acts as both a cholinesterase inhibitor and a nicotinic receptor modulator had the best result. The cognitive effects of galantamine may be accentuated by its nicotinic allosteric agonist action, which can improve attention and memory. Furthermore, galantamine appears to more powerfully elevate frontal cortical dopamine levels than cholinesterase inhibitors such as donepezil. This biological effect may be significant since frontal dopaminergic deficits have been proposed to underlie cognitive impairment in schizophrenia.

Importantly, significant improvement in attentional set shifting was seen. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.

Patient with schizophrenia manifest signs of a dysregulation of the NPY system. Extensive preclinical studies suggest that the neuropeptide Y (NPY) counteracts the behavioral consequences of stress and anxiety to and maintain emotional homeostasis. Thus it is involved in stress regulation and coping.

Treatment of Cognition in Schizophrenia

Стратегии лечения тиков при синдроме Туретта

The majority of treatment options for tics are pharmacological. The most commonly prescribed drugs are primarily dopamine antagonists, such as neuroleptics (e.g. haloperidol), benzamides (e.g. sulpiride) or atypical antipsychotics (e.g. risperidone). Other agents that may be efficacious include drugs which modulate noradrenaline (e.g. clonidine), GABA (e.g. benzodiazepines) and acetylcholine (e.g. nicotine). Nonpharmacological interventions include behavioural approaches such as habit reversal training and exposure response prevention therapy. Surgical techniques involving deep brain stimulation (DBS) of the thalamus or globus pallidus may also be considered for severe, treatment refractory patients. Some of the more recent treatments that have been trialled include electroconvulsive therapy and repetitive transcranial magnetic stimulation.

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Treatment Strategies for Tics in Tourette Syndrome