Smoking In Schizophrenia Patients Research Articles

Smoking affects the association between cognitive impairment and P50 inhibition defects in patients with chronic schizophrenia: A case-control study.

Smoking affects sensory gating, as assessed by the event related potential P50, which is evoked by auditory stimuli and is considered to be involved in the pathophysiology of schizophrenia (SCZ). However, few studies have compared sensory gating and cognitive performance between smoking and non-smoking SCZ patients in the Chinese Han population. We recruited two groups of Chinese subjects: 128 male chronic SCZ patients and 76 male healthy controls, measuring cognition with the MATRICS Consensus Cognitive Battery (MCCB) and sensory gating with the P50 EEG components. Based on their smoking status, they were further divided into 4 subgroups: smoking SCZ patients, non-smoking SCZ patients, smoking healthy controls, and non-smoking healthy controls. We assessed psychopathological symptoms of the patients using the Positive and Negative Syndrome Scale (PANSS). Compared with healthy controls, SCZ patients had lower MCCB total score and scores of all 10 tests (all p<0.05), while SCZ patients had higher S2 amplitudes and P50 ratios (both p<0.05). When comparing smoking versus non-smoking SCZ patients, non-smokers had significantly better spatial span (p<0.05). Furthermore, the S1 amplitude was negatively correlated with the Brief Visuospatial Memory Test (BVMT-R) in smoking patients (p<0.05), while the S1 latency was negatively correlated with spatial span in non-smoking patients (p<0.01). Our finding shows a difference in the relationship between sensory gated P50 and cognition in smoking and non-smoking SCZ patients, suggesting that nicotine may improve cognitive and P50 deficits in SCZ patients.

Smoking Affects the Patterns of Metabolic Disorders and Metabolic Syndrome in Patients With First-Episode Drug-Naive Schizophrenia: A Large Sample Study Based on the Chinese Han Population.

ObjectiveAlthough metabolic disorders and smoking are common in schizophrenia, few studies have investigated the effects of smoking on metabolic disorders or metabolic syndrome (MetS) in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. We sought to investigate the differences in metabolic disorders and MetS between smoking and nonsmoking FEDN schizophrenia patients.MethodsA total of 428 FEDN schizophrenia patients and 435 controls were recruited. Blood pressure, waist circumference, body mass index (BMI), lipid profiles, and glucose metabolism were measured. The psychopathology was evaluated by Positive and Negative Syndrome Scale.ResultsFEDN schizophrenia patients had a higher smoking rate than controls (23.8% vs 14.0%, P < .001). After adjusting for confounding variables, the prevalence of MetS, overweight, hypertension, hypertriglyceridemia, elevated insulin, and insulin resistance in smoking patients was higher than those in nonsmoking patients, while overweight and hypertension were higher in the smoking controls than in nonsmoking controls (all P < .05). In smoking patients, triglyceridemia, high-density lipoprotein cholesterol, and fasting blood glucose were the main contributing components to MetS, while in nonsmoking patients, waist circumference, systolic blood pressure, triglyceridemia, high-density lipoprotein cholesterol, and fasting blood glucose were the main contributing components to MetS. In smoking patients, BMI and homeostatic model assessment for insulin resistance were associated factors of MetS (both P < .05). In nonsmoking patients, sex, BMI, insulin, and homeostatic model assessment for insulin resistance were associated factors of MetS (all P < .05).ConclusionsOur study indicates that smoking schizophrenia patients have a higher prevalence of MetS and metabolic disorders than nonsmoking patients. Moreover, smoking and nonsmoking patients have different contributing components and associated factors for MetS.

Increased risk of smoking-related illnesses in schizophrenia patients: A nationwide cohort study

BackgroundSchizophrenia patients smoke at three times the rate of the general population, and are more susceptible to smoking-related illnesses. The goal of the current study was to evaluate the cumulative probability of chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD) following first documentation of smoking among schizophrenia patients as compared to smoking healthy controls. MethodsA nationally representative cohort study was designed to assess the odds and cumulative probability of COPD and IHD among individuals with schizophrenia (n = 10,502) and a matched-sample of smoking healthy controls (n = 10,502). Hierarchical logistic regressions and Kaplan-Meier regression models were used to compare odds and cumulative probabilities across the two groups. ResultsAfter adjusting for clinical and demographic factors, smoking schizophrenia patients had a higher probability of receiving a diagnosis of COPD than smoking healthy controls (OR 2.14, 95%CI 1.51–3.01, p < 0.001). The probability of having COPD increased more rapidly in smoking schizophrenia patients, yet the opposite trajectory prevailed for IHD, showing a decreased cumulative probability in smoking schizophrenia patients compared to smoking healthy controls. DiscussionSchizophrenia has a unique contribution to the facilitation of COPD, which extends beyond the effect of smoking, or other clinical and demographic risk factors. Differential smoking patterns could potentially account for this effect. The differential pattern of IHD should be subjected to further research, as our results might indicate that schizophrenia patients are underdiagnosed with IHD, and may be even less diagnosed as a function of time and chronicity.

Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia.

Patients with schizophrenia (SCZ) smoke at a rate of 4-5 times higher than the general population, contributing to negative health consequences in this group. One possible explanation for this increased smoking is that individuals with SCZ find nicotine (NIC) more reinforcing. However, data supporting this possibility are limited. The present experiments examined self-administration of NIC, alone or in combination with other reinforcers, across a range of doses in the methylazoxymethanol acetate (MAM) rodent model of SCZ. MAM and control animals did not differ in NIC self-administration across a range of doses and schedules of reinforcement, in both standard 1-hour self-administration sessions and 23-hour extended access sessions. However, MAM animals responded less for sucrose or reinforcing visual stimuli alone or when paired with NIC. To the extent that MAM-treated rats are a valid model of SCZ, these results suggest that increased NIC reinforcement does not account for increased smoking in SCZ patients. This study is the first to utilize nicotine self-administration, the gold standard for studying nicotine reinforcement, in the methylazoxymethanol acetate model of schizophrenia, which is arguably the most comprehensive animal model of the disease currently available. Our assessment found no evidence of increased nicotine reinforcement in methylazoxymethanol acetate animals, suggesting that increased reinforcement may not perpetuate increased smoking in schizophrenia patients.

Psychopathology and extrapyramidal side effects in smoking and non-smoking patients with schizophrenia: Systematic review and meta-analysis of comparative studies

The association between smoking and psychopathology and extrapyramidal side effects (EPSE) in schizophrenia has been controversial. This systematic review and meta-analysis compared psychopathology and EPSE between smoking and non-smoking schizophrenia patients. The PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science databases were independently and systematically searched by two researchers to identify relevant articles. Standardized mean differences (SMDs) and their 95% confidence intervals (CI) were calculated with random effect models. Subgroup and meta-regression analyses were performed to explore sources of heterogeneity. The systematic review and meta-analysis included 29 studies that compared psychotic, depressive and anxiety symptoms and EPSE between smoking (n = 3591) and non-smoking schizophrenia patients (n = 2980). Smoking patients had significantly more severe positive symptoms (24 studies; SMD = 0.33, 95% CI: 0.16 to 0.50, P < 0.001), but less severe EPSE (7 studies; SMD = −0.20, 95% CI: −0.38 to −0.02, P = 0. 03). No significant group differences in negative, depressive and anxiety symptoms were found. In conclusion, this systematic review and meta-analysis found that smoking schizophrenia patients had more severe positive symptoms but less severe EPSE than non-smoking patients.

Cognitive functions in smoking and non-smoking patients with schizophrenia: A systematic review and meta-analysis of comparative studies

The “Self-medication hypothesis” that has been developed to explain the effect of nicotine in improving aspects of cognitive impairment in schizophrenia remains controversial. This systematic review and meta-analysis compared cognitive functions between smoking and non-smoking schizophrenia patients. The PubMed, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases were systematically and independently searched. Basic demographic and clinical characteristics, smoking history and cognitive performance were recorded. Seven of the 11 studies included in the study, had meta-analyzable data. Compared to non-smoking schizophrenia patients, their smoking counterparts showed significant deficits on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)-immediate memory (n = 739), the RBANS-total score (n = 739) and the Continuous Performance Test-Identical Pairs (n = 157). Two of the 4 studies without meta-analysable data did not report significant group difference in performance on the Wechsler Digit Span Task and the Beck Cognitive Insight Scale, while the other 2 studies found that non-smokers outperformed than smokers in problem solving and visual learning. In conclusion, this systematic review and meta-analysis found that smoking schizophrenia patients had worse performance in certain cognitive tasks than non-smoking patients, casting doubts on the validity of the “self-medication hypothesis” that needs to be further examined.

Smoking restores impaired LTD-like plasticity in schizophrenia: a transcranial direct current stimulation study.

Impaired neuroplastic responses following noninvasive brain stimulation have been reported repeatedly in schizophrenia patients. These findings have been associated with deficits in GABAergic, glutamatergic, and cholinergic neurotransmission. Although various neurophysiological studies have indicated a relationship between nicotine and neuroplasticity in healthy individuals, the present study is the first investigation into the impact of nicotine on LTD-like plasticity in patients with schizophrenia. Cortical excitability and cortical plasticity were explored in 30 schizophrenia patients (17 smoker, 13 nonsmoker) and 45 healthy controls (13 smoker, 32 nonsmoker) by using single-pulse transcranial magnetic stimulation (TMS) before and following cathodal transcranial direct current stimulation (tDCS) applied to the left primary motor cortex. Our analysis revealed abolished LTD-like plasticity in nonsmoking schizophrenia patients. However, these plasticity deficits were not present in smoking schizophrenia patients. In healthy controls, significant MEP reductions following cathodal tDCS were observed in nonsmoking individuals, but only trend-level reductions in smokers. In smoking schizophrenia patients, the severity of negative symptoms correlated positively with reduced neuroplasticity, whereas nonsmoking patients displayed the opposite effect. Taken together, the data of our study support the notion of an association between chronic smoking and the restitution of impaired LTD-like plasticity in schizophrenia patients. Although replication and further research are needed to better understand this relationship, our findings indicate that nicotine intake might stabilize the impaired inhibition-facilitation balance in the schizophrenic brain through a complex interaction between cortical plasticity, and GABAergic and cholinergic neurotransmission, and might explain the reduced prevalence of negative symptoms in this population.

Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia.

The prevalence of smoking in schizophrenia patients is exceptionally high; it is not known why but many researchers suggest that smoking constitutes a form of self-medication. Among the symptoms of schizophrenia that may be improved by nicotine are cognitive deficits. Hence, we studied the effects of long-term nicotine administration on cognition in a genetic animal model of schizophrenia susceptibility, G72-transgenic (G72Tg) mice. The effect of long-term nicotine or saline, administered by osmotic minipumps, on different cognitive domains was assessed in G72Tg mice and controls using a battery of behavioural tests. To investigate the mechanism underlying phenotypic differences, quantitative autoradiographic mapping of nACh receptor subtypes was performed in forebrain structures to explore effects of chronic nicotine exposure on nACh receptor density in wild-type (WT) and G72Tg mice. Genotype significantly affected the cognitive effects of chronic nicotine administration. Whereas chronic nicotine disrupted cognitive performance in WT mice, it was effective at restoring impaired prepulse inhibition, working memory and social recognition in G72Tg mice. However, long-term spatial learning was further impaired by nicotine in transgenic animals. In contrast, associative learning was protected by G72-expression against the adverse nicotine effects seen in WT animals. G72-expression did not decisively influence nicotine-induced up-regulation of the α4β2*subtype, whereas α7nACh receptor density was differentially altered by genotype or by a genotype·treatment interaction in specific brain areas, most notably hippocampal subregions. Our data support the hypothesis that nicotine self-medication of schizophrenics improves cognitive symptoms, possibly by facilitating nicotine-induced α7nACh receptor activation in the hippocampus.

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients

High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) seemed to decrease tobacco consumption and craving in nicotine-dependent people without psychiatric disorder or otherwise healthy people. Even if the prevalence of cigarette smoking in schizophrenia patients is high and estimated to be between 45% and 88%, this technique has not been systematically studied in this indication in schizophrenia yet. The aim of this study was to test the ability of high-frequency (10Hz) rTMS over the left DLPFC to decrease cigarette consumption in schizophrenia patients. The study included 35 male schizophrenia patients on stable antipsychotic medication. The patients were divided into two groups: the first (18 patients) were actively stimulated and the second (17 patients) underwent sham (placebo) stimulation. The sham rTMS was administered using a purpose-built sham coil that was identical in appearance to the real coil and made the same noise but did not deliver a substantial stimulus. The rTMS was administered at the stimulation parameters: location (left dorsolateral prefrontal cortex: DLPFC), intensity of magnetic stimulation in % of motor threshold (110%), stimulation frequency (10Hz), number of trains (20), single train duration (10s), inter-train interval (30s), and total number of stimulation sessions (21). In each stimulation session, 2000TMSpulses were given, with a total of 42,000pulses per treatment course. Patients noted the number of cigarettes smoked in the 7days before treatment, during the whole stimulation treatment (21days), and again for a 7-day period after treatment. Cigarette consumption was statistically significantly lower in the actively stimulated patients than in the sham rTMS group as early as the first week of stimulation. No statistically relevant correlations were found in the changes of ongoing negative or depressive schizophrenia symptoms and the number of cigarettes smoked. High-frequency rTMS over the left DLPFC has the ability to decrease the number of cigarettes smoked in schizophrenia patients.

Inverse association between 18-carbon trans fatty acids and intelligence quotients in smoking schizophrenia patients

This study aimed to investigate polyunsaturated (PUFA) and trans isomeric fatty acid status in schizophrenia patients. Fatty acid composition of plasma phospholipids (PL) and triacylglycerols (TG) was analyzed by gas chromatography in 29 schizophrenia patients and 15 healthy controls. We found no difference in PL n-3 fatty acid status between the two groups, while the values of 22:5n-6 were significantly higher in patients with schizophrenia than in controls. In TG, values of docosatrienoic acid (20:3n-3) and docosapentaenoic acid (20:5n-3) were significantly higher in schizophrenia patients than in controls. We found no difference in the trans fatty acid status between patients and controls. In smoking schizophrenia patients significant negative correlations were detected between Wechsler adult full-scale intelligence quotients and values of total trans fatty acids in PL lipids, whereas no such correlation was seen either in non-smoking schizophrenia patients, or in healthy controls. While data obtained in the present study fail to furnish evidence for n-3 PUFA supplementation to the diet of patients with schizophrenia, they indicate that in smoking schizophrenia patients high dietary exposure to trans fatty acids is associated with lower intelligence quotients.

Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls

Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. So far, the published studies of nicotine effects on antisaccade performance in schizophrenia patients only tested participants who were deprived smokers. Thus, we aimed to test both smoking and non-smoking patients as well as healthy controls in order to extend previous findings. Moreover, we employed a paradigm using standard and delayed trials. We hypothesized that, if nicotine is a genuine cognitive enhancer, its administration would improve antisaccade performance both in smoking and non-smoking participants. A total of 22 patients with schizophrenia (12 smokers and 10 non-smokers) and 26 controls (14 smokers and 12 non-smokers) completed the study. The effects of a nicotine patch (14mg for smokers, 7mg for non-smokers) on antisaccade performance were tested in a randomized, double-blind, placebo-controlled, cross-over trial. Schizophrenia patients made significantly more antisaccade errors than controls (p=0.03). Both patients and controls made fewer antisaccade errors in the delayed trials than in the standard trials (p<0.0001). Nicotine significantly reduced antisaccade error rate in the standard trials, but not in the delayed trials (p=0.02). Smoking status did not influence the nicotine effect on antisaccade error rate (p=0.10) indicating an equal procognitive effect of nicotine in smokers and non-smokers. Overall the present findings indicate that beneficial effects of nicotine on antisaccade performance are not confined to smoking schizophrenia patients. Instead, the findings likely represent genuine nicotine-induced enhancement of cognitive performance.

Acute nicotine improves social decision-making in non-smoking but not in smoking schizophrenia patients

Schizophrenia patients are characterized by severe social impairments. Recently, social cognition has been put forward as an important mediator in schizophrenia between the often-reported neurocognitive deficits and functional outcome and is thus an important target for treatments. Nicotine has been reported to improve neurocognitive processes in schizophrenia patients but no studies have investigated possible nicotine-induced facilitation of social cognition. The current placebo-controlled crossover study aimed at bridging this gap by investigating whether the administration of active (1 mg or 2 mg) or placebo oromucosal nicotine spray resulted in improved social decision-making in non-smoking (N = 15) and smoking (N = 16) schizophrenia patients. All patients played the role of responder in a variant of the ultimatum game that allowed detailed measurements of fairness and intentionality considerations. The results showed impaired social decision-making in the non-smoking patients under placebo, but not in the smoking patients. Interestingly, this impairment normalized after administration of 1 mg of nicotine, but not after 2 mg of nicotine. Nicotine had no effect on performance in the smoking patients. The present study indicates that nicotine improves social decision-making in non-smoking patients. The present results suggest that acute nicotine effects may result in a facilitation of proactive control through improved attentional processes. However, the efficacy seems limited and although nicotine may thus be an interesting target for (social) cognitive enhancement in the subset of patients that do not smoke, more research is needed on the long-lasting effects of nicotine-based treatments.

Effects of nicotine on social cognition, social competence and self-reported stress in schizophrenia patients and healthy controls

More than 80 % of patients diagnosed with schizophrenia are nicotine-dependent. Self-medication of cognitive deficits and an increased vulnerability to stress are discussed as promoting factors for the development of nicotine dependence. However, the effects of nicotine on social cognition and subjective stress responses in schizophrenia are largely unexplored. A 2 × 2-factorial design (drug × group) was used to investigate the effects of nicotine versus placebo in smoking schizophrenia patients and healthy controls after 24 h of abstinence from smoking. Participants performed a facial affect recognition task and a semi-standardized role-play task, after which social competence and self-reported stress during social interaction were assessed. Data analysis revealed no significant group differences in the facial affect recognition task. During social interaction, healthy controls showed more non-verbal expressions and a lower subjective stress level than schizophrenia patients. There were no significant effects of nicotine in terms of an enhanced recognition of facial affect, more expressive behaviour or reduced subjective stress during social interaction. While schizophrenia patients unexpectedly recognized facial affect not significantly worse than healthy controls, the observed group differences in subjective stress and non-verbal expression during social interaction in the role-play situation are in line with previous findings. Contrary to expectations derived from the self-medication hypothesis, nicotine showed no significant effects on the dependent variables, perhaps because of the dosage used and the delay between the administration of nicotine and the performance of the role-play.

P.3.e.012 Cognitive effects of varenicline treatment in smoking schizophrenia patients

P.3.e.012 Cognitive effects of varenicline treatment in smoking schizophrenia patients

Relationship between Smoking and Family History of Smoking in Schizophrenia Patients

The rate of smoking is known to be high in patients with schizophrenia. The purpose of this study was to quantitatively examine the relationship between smoking and family history of smoking in patients with schizophrenia. The sample consisted of 172 patients (mean age: 54 years, 55% male) hospitalized in a general psychiatric hospital. They were asked by a physician whether they smoked. Family histories of smoking and schizophrenia were assessed among first- and third-degree relatives. Ninety-eight patients (57%) were identified as having smoked at some point. Multiple logistic regression analysis showed that smoking was significantly associated with family histories of smoking among both first- and third-degree relatives, controlling for the effects of age, sex, and family history of schizophrenia. The smoking rates were significantly higher in those with a family history of smoking, but not a family history of schizophrenia, than among those without a family history of either smoking or schizophrenia. However, this difference did not reach statistical significance among those with a family history of schizophrenia. Smoking is greatly influenced by family history of smoking in patients with schizophrenia, especially among those without a family history of schizophrenia. The association between smoking and family history of smoking was inconclusive among those patients with schizophrenia who also had a family history of schizophrenia.

Smoking and Schizophrenia Independently and Additively Reduce White Matter Integrity Between Striatum and Frontal Cortex

Although schizophrenia patients are at high risk for tobacco use, the neurobiological basis of this comorbid association is not clear. White matter abnormalities have been described independently in schizophrenia and smoking cohorts. We sought to determine whether smoking and schizophrenia are associated with similar white matter abnormalities that could be biomarkers for the high risk of smoking in schizophrenia. Whole brain white matter integrity (fractional anisotropy) was measured in 46 schizophrenia patients (32 smokers and 14 nonsmokers) and 69 healthy age-matched control subjects (48 smokers and 21 nonsmokers). Schizophrenia and smoking status were independently and additively associated with reduced fractional anisotropy in left anterior thalamic radiation/anterior limb of the internal capsule, and significant fractional anisotropy decreases were identified in the bilateral uncinate fasciculus/inferior fronto-occipital fasciculus in schizophrenia and the left prefrontal area in smoking status separately. Common and distinct patterns of impaired white matter are associated with schizophrenia and smoking. Particularly, the anatomic congruence of an additive white matter abnormality in the anterior thalamic radiation/anterior limb of the internal capsule suggests that this abnormal fiber connectivity between frontal cortex and striatum/thalamus may be a biomarker for the increased comorbid smoking in schizophrenia patients.

Validity of self‐reported smoking in schizophrenia patients

It is important to evaluate smoking status among schizophrenia patients because such patients are highly inclined to take up smoking, but only a few studies have focused on the validity of self-reported smoking in relation to schizophrenia. The aim of the present study was therefore to determine the validity of self-reported smoking and to investigate whether self-reported smoking is biased in schizophrenia patients. A total of 158 schizophrenia patients answered self-rated questions of smoking status, and the level of carbon monoxide (CO) in expired air was measured. The relationship of the self-reported smoking to the CO levels was determined, and interaction of the disease duration and education level on this relationship was evaluated using correlation and receiver operating characteristic analyses. The CO levels in the expired air were found to be positively related to the self-reported data (P < 0.01). The stratified data on the duration of schizophrenia indicated that the positive relationship between self-reported smoking and the CO concentration became less obvious with the increase in duration of schizophrenia (P(trend) < 0.01). In contrast, the stratified data on education level did not indicate any such significant modifying effect. Although self-reporting is useful for evaluating smoking status, psychiatrists should use objective methods of measurement to assess the smoking status of chronic schizophrenia patients.

Differential effects on T-cell function following exposure to serum from schizophrenia smokers

Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effects of 'smoking-conditioned' serum obtained from schizophrenia and control subjects on healthy T cell in vitro. We found that T-cell proliferation was significantly increased following exposure to serum from smoking schizophrenia patients whereas no effect was observed when using serum from smoking control subjects or non-smoking patients and controls. We eliminated the possibility that these effects were due to quantitative differences in cigarette consumption as serum levels of the stable nicotine metabolite cotinine were similar in schizophrenic and control smokers. Molecular characterization showed that serum from patient smokers increased expression of T-cell activation markers CD69(high), CD25(high), co-stimulatory molecules CD26+, CD27+ and CD28+, and decreased T-cell receptor complex components TCRalpha/beta and CD3. Moreover, analysis of supernatants collected after T-cell exposure to serum from smoking patients showed a time-dependent decline in interleukin (IL)-2 levels, suggesting that the proliferation effect is promoted by enhanced IL-2 processing. These results suggest that cigarette smoking has selective effects on serum components that, in turn, lead to altered immune function in schizophrenia patients relative to healthy subjects. Further studies aimed at characterizing these components could result in a better understanding of the onset and aetiology of schizophrenia and potentially lead to novel therapeutic strategies.

Accentuated behavioral sensitization to nicotine in the neonatal ventral hippocampal lesion model of schizophrenia

The prevalence of smoking in schizophrenia patients far exceeds that in the general population. Increased vulnerability to nicotine and other drug addictions in schizophrenia may reflect the impact of developmental limbic abnormalities on cortical–striatal mediation of behavioral changes associated with drug use. Rats with neonatal ventral hippocampal lesions (NVHLs), a neurodevelopmental model of schizophrenia, have previously been shown to exhibit altered patterns of behavioral sensitization to both cocaine and ethanol. This study explored nicotine sensitization in NVHLs by testing locomotor activity of NVHL vs. SHAM-operated controls over 3 weeks in response to nicotine (0.5 mg/kg) or saline injections (s.c.) followed by a nicotine challenge delivered to all rats 2 weeks later. At the beginning of the initial injection series, post-injection locomotor activation was indistinguishable among all treatment groups. However, nicotine but not saline injections produced a progressive sensitization effect that was greater in NVHLs compared to SHAMs. In the challenge session, rats with previous nicotine history showed enhanced locomotor activation to nicotine when compared to drug naïve rats, with NVHL-nicotine rats showing the greatest degree of activity overall. These results demonstrate that NVHLs exhibit altered short- and long-term sensitization profiles to nicotine, similar to altered long-term sensitization profiles produced by cocaine and ethanol. Collectively, these findings suggest the neurodevelopmental underpinnings of schizophrenia produce enhanced behavioral sensitization to addictive drugs as an involuntary and progressive neurobehavioral process, independent of the acute psychoactive properties uniquely attributed to nicotine, cocaine, or alcohol.

P.3.c.016 The relation between insulin receptor substrate-1 gene and olanzapine-induced weight gain and smoking in schizophrenia patients

P.3.c.016 The relation between insulin receptor substrate-1 gene and olanzapine-induced weight gain and smoking in schizophrenia patients