Robert C. Smith

Effects of Cigarette Smoking and Nicotine Nasal Spray on Psychiatric Symptoms and Cognition In Schizophrenia

Schizophrenic patients have among the highest rates of smoking of any group of patients. Previous studies have identified psychophysiological and potential nicotinic receptor abnormalities which may be associated with this phenomenon. The effects of acute smoking or acute administration of nicotine nasal spray, after smoking abstinence, on negative symptoms and neurocognitive function have been less extensively studied in experimental designs. This study investigated the effects of smoking of high nicotine or denicotinized cigarettes, and receiving active or placebo nicotine nasal sprays, on positive and negative symptoms and cognitive functions in schizophrenic patients. The study utilized a placebo controlled crossover experimental design with pre- and post-drug evaluations on each experimental day. Smoking high nicotine cigarettes decreased negative symptoms more than denicotinized cigarettes, but smoking neither cigarette changed scores of positive symptoms, anxiety, or depression. Active nicotine nasal spray did not differentially decrease negative symptoms compared with placebo, but did improve performance on a spatial organization task, and tended to improve some measures of verbal memory and two-choice reaction time in schizophrenic patients. Both high and denicotinized cigarettes improved performance on the spatial processing task, but there was no statistically significant differential drug (Cigarette type) effect. These results suggest that acute smoking of cigarettes may transiently decrease negative symptoms in patients with schizophrenia, but it is unclear whether this effect is attributable to nicotine, other components of cigarettes, or the act of smoking. Nicotine nasal spray may modestly improve some selected aspects of cognitive function in schizophrenia.

Effects of phencyclidine on [3H]catecholamine and [3H]serotonin uptake in synaptosomal preparations from rat brain

Abstract Phencyclidine inhibited uptake in vitro of [3H]norepinephrine ( ic 50 0.52 μM), [3H]dopamine ( ic 50 0.73 μM) and [3H]serotonin ( ic 50 0.80 μM) in crude synaptosomal preparations from rat brain through a competitive mechanism. Phencyclidine was fairly similar in potency to d-amphetamine and methylphenidate in inhibiting catecholamine uptake but was 8 times more potent than d-amphetamine and 34 times more potent than methylphenidate in inhibiting [3H]serotonin uptake.

Effects of Nicotine Nasal Spray on Cognitive Function in Schizophrenia

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 Conners 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.

Behavioral evidence for supersensitivity after chronic administration of haloperidol, clozapine, and thioridazine

Abstract Rats administered chronic neuroleptics for 6–7 weeks-- haloperidol (2.5 mg/rat or 1 mg/kg), clozapine (25 mg/kg), or thioridazine (20 mg/kg)--after termination of chronic drug treatment exhibited greater apomorphine-induced stereotyped behavior than their saline controls. Rats treated with thioridazine or clozapine, but not haloperidol, also showed increases in locomotor activity during withdrawal. These findings indicate that behavioral supersensitivity may develop after chronic clozapine treatment as well as after chronic haloperidol.

Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder

OBJECTIVEnVarenicline has been shown to be an effective anti-smoking treatment in smokers without identified psychiatric illness, and the drugs pharmacology suggests possibilities of pro-cognitive effects. However, recent reports suggest varenicline may have the potential for important psychiatric side-effects in some people. We present the first prospective quantitative data on the effects of varenicline on cognitive function, cigarette smoking, and psychopathology in a small sample of schizophrenic patients.nnnMETHODnFourteen schizophrenic smokers were enrolled in an open-label study of varenicline with a pre-post design. Measures of cognitive function (RBANS, Virtual Water-Maze Task), cigarette smoking (cotinine levels, CO levels, self-reported smoking and smoking urges), and psychopathology (PANSS) were evaluated prior to and during treatment with varenicline. Data on psychopathology changes among schizophrenic smokers in another drug study, in which patients were not receiving varenicline, were used for comparison.nnnRESULTSn12 patients completed the study, and 2 patients terminated in the first two weeks of active varenicline because of complaints of nausea or shaking. Varenicline produced significant improvements in some cognitive test scores, primarily associated with verbal learning and memory, but not in scores on visual-spatial learning or memory, or attention. Varenicline significantly decreased all indices of smoking, but did not produce complete smoking abstinence in most patients. During treatment with varenicline there were no significant increases in psychopathology scores and no patient developed signs of clinical depression or suicidal ideation.nnnCONCLUSIONSnOur small prospective study suggests that treatment with varenicline appears to have some beneficial cognitive effects which need to be confirmed in larger studies with additional neuropsychological tests. Varenicline appears to have some anti-smoking efficacy in schizophrenia but longer studies are needed to determine whether it will produce rates of smoking abstinence similar to those found in control smokers. Treatment with varenicline may not increase psychopathology or depression in most patients with schizophrenia, but we cannot accurately estimate the absolute risk of a potentially rare side-effect from this small sample.

Effect of apomorphine on schizophrenic symptoms

The effects of apomorphine on psychotic symptoms were evaluated in chronic schizophrenic patients using double-blind placebo controlled procedures. Although on the basis of dopamine theory of schizophrenia, apomorphine was expected to increase schizophrenic symptoms, in this study apomorphine substantially reduced psychotic symptoms in some chronic schizophrenic patients. No patient showed the substantial increase in psychotic symptoms previously demonstrated after the administration of IV methylphenidate. These clinical effects of apomorphine in schizophrenia may be relevant to recent pharmacological research which has indicated that apomorphine also has potent effects on presynaptic dopamine neurons, in addition to its previously described postsynaptic receptor stimulation.

Comparative effects of d-amphetamine, l-amphetamine and methylphenidate on mood in man

The comparative effects of d-amphetamine, l-amphetamine, and methylphenidate were assessed in 16 normal subjects, using a double-blind, crossover placebo-controlled design. Within the dose range tested, the efficacy ratio of d-amphetamine: l-amphetamine was about 2:1, and graphic presentation of dose response scores indicated a relatively small difference in potency between the amphetamine isomers. Methylphenidate was intermediate in efficacy between d-amphetamine and l-amphetamine. The efficacy ratios for d-amphetamine: l-amphetamine on increasing euphoric mood in man were similar to the previously reported ratios of these two isomers in inducing or exacerbating psychosis in humans. These findings do not support the suggestion, made by Snyder and others, that the differential effects of d-amphetamine vs. l-amphetamine on a specific type of behavior in man could be utilized to infer the predominance of noradrenergic vs. dopaminergic mediation of amphetamines effects on this behavior.

Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenic patients

Some reports have indicated increased rates of diabetes and increased prevalence of glucose and lipid abnormalities during treatment with second-generation antipsychotics, with most concern raised about clozapine and olanzapine. Most of the findings have come from case reports, retrospective examination of laboratory values, and analysis of health-care claims databases. This study investigated fasting levels of glucose, lipids, and leptin in a non-randomized, cross- sectional study of 210 patients, with schizophrenic or schizoaffective disorder, treated with a single antipsychotic medication - clozapine, risperidone, olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed in a subset of patients. In this sample most mean fasting glucose and lipid levels were within the normal range and were not significantly different across the four drug treatment groups. Patients treated with clozapine and olanzapine had higher triglyceride levels than risperidone patients. In patients receiving a GTT, risperidone-treated patients had higher glucose levels at 1 h than patients treated with olanzapine, and there were more patients on risperidone who met American Diabetes Association glucose metabolic criteria for diagnosis of diabetes. Although there were no significant differences in age or body mass index among the four drug groups, we cannot rule out some potential biasing factors we did not assess which could potentially influence our results. These include unknown physician preference in drug selection based on their beliefs about the weight-inducing or diabetes potential of different antipsychotics, differences in visceral fat, and differences in patients antipsychotic drug history.

ANATOMICAL ALIGNMENT FOR THE CORRECTION OF BURIED PENIS

PURPOSEnWe report a straightforward surgical technique for the correction and anatomical alignment of the skin in patients with various degrees of buried penis.nnnMATERIALS AND METHODSnA combined series of 74 patients 7 months to 10 years old who were treated for buried penis at 2 institutions during a 7-year period. Patients presented with various symptoms, including balanitis, urinary tract infection, painful voiding, ballooning of the foreskin and urinary retention. In 29 patients (38%) trapped penis was due to previous circumcision. In our estimation the major anatomical defect in buried penis is an insufficient attachment of the dartos fascia and penile skin to Bucks fascia. Our technique involves making a circumferential incision of the inner preputial skin layer proximal to the corona, unfurling it from the shaft skin and leaving a coronal collar of approximately 1 cm. The annular band that usually constricts the corpora on retraction of the penile skin is incised, and the remaining proximal penile skin and dartos fascia are dissected off Bucks fascia proximally to the base of the penis. The penile dermis is sutured to the lateral aspect of the tunica albuginea at the penopubic junction and mid shaft of the penis. This technique restores normal anatomical relationships with excellent cosmetic results and negligible complications.nnnRESULTSnAt a median 5-year followup cosmesis was excellent in all cases. Two patients with micropenis who required revision responded to endocrine therapy.nnnCONCLUSIONSnExcellent cosmetic results were obtained in all cases using this surgical technique.

Effects of transcranial direct current stimulation (tDCS) on cognition, symptoms, and smoking in schizophrenia: A randomized controlled study

Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved. Transcranial direct current stimulation (tDCS) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a randomized controlled study for these effects in schizophrenia. We conducted a randomized double-blind, sham-controlled study of the effects of 5 sessions of tDCS (2 milliamps for 20minutes) on cognition, psychiatric symptoms, and smoking and cigarette craving in 37 outpatients with schizophrenia or schizoaffective disorder who were current smokers. Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery (MCCB), with the primary outcome measure, the MCCB Composite score. Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score (p=0.008) and on the MCCB Working Memory (p=0.002) and Attention-Vigilance (p=0.027) domain scores, with large effect sizes. MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels (α=0.05). There were no statistically significant effects on secondary outcome measures of psychiatric symptoms (PANSS scores), hallucinations, cigarette craving, or cigarettes smoked. The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia outpatients that should be further investigated.