Posttraumatic stress disorder,smoking, and cortisol in a community sample of pregnant women

Background

The prevalence of posttraumatic stress disorder (PTSD) in the United States is higher among pregnant women than women generally. PTSD is related to adverse birth outcomes via physiological and behavioral alterations, such as smoking.

Methods

We utilize salivary cortisol measures to examine how traumatic stress, smoking and the hypothalamic–pituitary–adrenal axis interact. Pregnant women (n = 395) gave cortisol specimens as part of a cohort study of PTSD and pregnancy at three health systems in the Midwestern United States. Women were divided into three groups: nonsmokers, quitters (who stopped smoking during pregnancy), and pregnancy smokers. Mean cortisol values at three points, sociodemographics, trauma history, and PTSD were compared across groups. We assessed the association of smoking group and PTSD with late afternoon cortisol levels.

Results

Smokers, quitters, and nonsmokers differed on demographic risk factors and PTSD symptom load. Late afternoon and bedtime cortisol measures were significantly positively correlated with smoking in pregnancy, with smokers with PTSD presenting the highest cortisol levels. Regression analysis showed that smoking in pregnancy was associated with higher late afternoon cortisol in an additive manner with PTSD symptoms.

Conclusions

Smoking appears to have a different relationship with cortisol level for those with and without PTSD. This is the first study to show additive effects of smoking and PTSD on cortisol levels in pregnant women. Since high cortisol, smoking, and PTSD have been shown to adversely affect perinatal outcomes, and since those continuing to smoke in pregnancy had the highest PTSD symptom load, PTSD-specific smoking cessation programs in maternity settings are warranted.     

Traumatic stress in rats induces noradrenergic-dependent long-term behavioral sensitization: role of individual differences and similarities with dependence on drugs of abuse

Rationale

The aim of this paper is to provide evidence for the hypothesis that posttraumatic stress disorder (PTSD) and drug addiction rely on common processes.

Objective

Our objective is to show that a noradrenergic-dependent behavioral sensitization occurs after the development of PTSD, in a way similar to that recently demonstrated after repeated drug injections.

Methods

Rats classified into high and low responders to novelty (HR/LR) were subjected to a single prolonged stress (SPS). Cross-sensitization was evaluated after d-amphetamine injection (1.0 mg/kg) in a locomotor activity test given either 4, 15, or 90 days later. To determine the involvement of the noradrenergic system, rats were injected with the α2-receptor agonist, clonidine (20 μg/kg), during the SPS. Subsequently, their auditory startle response (ASR) and cross-sensitization were assessed.

Results

SPS affected both the hypothalamic–pituitary–adrenal axis and the ASR, replicating some PTSD-like symptoms. Behavioral sensitization was found after 15, 21, and 90 days after the SPS in LR rats, and a behavioral desensitization in HR rats after 15 days. Clonidine delivered during the SPS prevented the behavioral sensitization in LR rats, as well as the effects on ASR in HR and LR rats.

Conclusions

Exposure to SPS is shown to affect behavior and induce a behavioral sensitization to d-amphetamine that is modulated by individual differences. Both of these effects depend on the noradrenergic system. Altogether, the present results (1) replicate findings obtained after repeated drug exposure and (2) strengthen our hypothesis of a common physiological basis between PTSD and drug addiction.     

Effect of aripiprazole, risperidone, and olanzapine on the acoustic startle response in Japanese chronic schizophrenia

Background  

Studies have also shown that differences in the kind of the antipsychotics influenced disruption of the sensorimotor gating system, including prepulse inhibition (PPI), acoustic startle reflex (ASR), and habituation (HAB). We investigated the influence on startle response in chronic schizophrenia in 20 patients with schizophrenia taking risperidone, 21 patients with schizophrenia taking olanzapine, and 20 patients with schizophrenia taking aripiprazole.     

Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD

Rationale Exaggerated acoustic startle is a prominent symptom of post-traumatic stress disorder (PTSD); however, its physiological basis is not well understood, and there are few available treatments. Neurobiological research has suggested that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA antagonist that also demonstrates potent anti-kindling effects and may, therefore, have promise in treating trauma-enhanced ASR.Objective To evaluate the ability of topiramate to attenuate stress-induced increases in ASR in a previously validated animal model of PTSD.Methods Male Sprague-Dawley rats (n=36) served as controls or received single prolonged stress (SPS). SPS consisted of 2 h restraint, forced swim and ether anesthesia, then a 7-day undisturbed period. Animals then received vehicle, 10 mg/kg or 30 mg/kg of topiramate orally, twice daily for 7 days. ASR was assessed for all animals before and after the study, in light and dark environments.Results SPS produced a sustained increase in the ASR in both environments, an effect that was significantly reduced by topiramate. Meanwhile the ASR of control animals remained unaffected by topiramate.Conclusions The current results provide one of the few demonstrations of a single stress episode producing sustained enhancement of ASR. In addition, topiramate demonstrates promise in treating exaggerated acoustic startle symptoms in PTSD or other stress-related disorders.     

Do ethnicity and gender moderate the influence of posttraumatic stress disorder on time to smoking lapse?

Background

Following a smoking cessation attempt, smokers with posttraumatic stress disorder (PTSD) experience smoking relapse at a higher and faster rate. Black ethnicity and female gender are also associated with lower success rates following smoking cessation. No study to date has prospectively examined how ethnicity and gender may moderate the effect of PTSD on smoking relapse. It was hypothesized that female gender and Black ethnicity would significantly predict early lapse after quitting; further, it was predicted that ethnicity and gender would moderate the effect of PTSD on relapse rate.

Methods

Smokers with PTSD (n = 48) and without PTSD (n = 56) completed ecological momentary assessment (EMA) the week after a quit date, and self-initiated EMA entries after smoking lapse. Smoking abstinence was biologically verified. The sample included Black (62%) and White (38%) participants, and was 50% female. Study hypotheses were tested with Cox proportional hazards regression modeling time to first smoking lapse.

Results

Study results confirmed the main hypothesis, with a significant PTSD × Ethnicity interaction emerging. The effect of PTSD on smoking relapse was significant for White participants but not for Black participants. No significant gender moderation was found.

Conclusion

Taken together, study results support previous research, and suggest that the relationship between smoking and PTSD is stronger for White smokers than for minorities. This study has significant implications for research in smoking and mental disease, as well as for smoking cessation treatments for Black smokers.     

Acoustic startle reduction in cocaine dependence persists for 1 year of abstinence

Rationale  

Chronic cocaine use results in long-lasting neurochemical changes that persist beyond the acute withdrawal period. Previous work from our group reported a profound reduction in the acoustic startle response (ASR) in chronic cocaine-dependent subjects in early abstinence compared to healthy controls that may be related to long-lasting neuroadaptations following withdrawal from chronic cocaine use.     

Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids

Rationale

Non-daily, or intermittent smokers (ITS), are increasingly prevalent. Their smoking may be more situational than that of daily smokers (DS), and thus is hypothesized to be more influenced by cues.

Objectives

To assess ITS’ response to cues, and compare it to that of DS.

Methods

Samples of 239 ITS and 207 DS (previously reported in Shiffman et al. 2012a) were studied in 2,586 laboratory cue-reactivity sessions. Craving (Questionnaire of Smoking Urges) and smoking (probability, latency, puff parameters, and carbon monoxide increases) in response to cues was assessed following exposure to neutral cues and cues related to smoking, alcohol, negative affect, positive affect, and smoking prohibitions. Mixed effects models, generalized estimating equations and random-effects survival analyses were used to assess response to cues and differences between DS and ITS.

Results

ITS’ craving increased following exposure to smoking and alcohol cues and decreased following positive affect cues, but cues had little effect on smoking behaviors. Cue reactivity was similar in ITS and DS. Among ITS, craving intensity predicted smoking probability, latency, and intensity, and the effects on latency were stronger among ITS than DS.

Conclusions

Contrary to hypotheses, ITS were not more responsive to laboratory cues than DS. Results show that ITS do experience craving and craving increases that are then associated with smoking.     

PTSD symptomatology and readiness to quit smoking among women with serious mental illness

Introduction

Posttraumatic stress disorder (PTSD) is a risk factor for tobacco addiction. The majority of research on PTSD and smoking has been conducted with men, particularly combat veterans, and little is known about the association among women. In a clinical sample of women civilian smokers with serious mental illness (SMI), we examined the prevalence of PTSD symptomatology and associations with physical and mental health functioning, co-occurring substance use, nicotine dependence, and readiness to quit smoking.

Methods

376 adult women smokers aged 18–73 were recruited from 7 acute inpatient psychiatry units and screened by diagnostic interview for current PTSD symptomatology (PTSD⁺). In multiple regressions, we examined the associations of screening PTSD⁺ with physical and mental health functioning; past-month drug use; past-year substance use disorders; nicotine dependence and readiness to quit smoking.

Results

Nearly half the sample (43%) screened PTSD⁺, which was significantly associated with the use of stimulants (OR = 1.26) and opiates (OR = 1.98), drug use disorders (OR = 2.01), and poorer mental health (B = − 2.78) but not physical health functioning. PTSD⁺ status was unrelated to nicotine dependence, but predicted greater desire to quit smoking (B = 2.13) and intention to stop smoking in the next month (OR = 2.21). In multivariate models that adjusted for substance use disorders, physical and mental health functioning, and nicotine dependence, screening PTSD⁺ remained predictive of greater desire and intention to quit smoking.

Conclusion

PTSD symptomatology was common in our sample of women smokers with SMI and associated with not only worse substance use and mental health, but also greater readiness to quit smoking, suggesting the need for and potential interest in integrative PTSD-addiction treatment among women.     

Effects of intravenous nicotine on prepulse inhibition in smokers and non-smokers: relationship with familial smoking

Rationale

The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing. Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex. However, it remains unclear whether these effects are related to smoking susceptibility.

Objectives

The current study examined the effects of intravenously delivered nicotine on PPI in smokers and non-smokers, as well as its association with a quantitative index of familial smoking.

Methods

The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions. Separate doses were used in smoker and non-smoker samples.

Results

Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives. Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking.

Conclusions

These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk.     

Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study

Using ambulatory methods for 1 day of monitoring, the authors of this study investigated the association between smoking and situational cues in 63 smokers with posttraumatic stress disorder (PTSD) and 32 smokers without PTSD. Generalized estimating equations contrasted 682 smoking and 444 nonsmoking situations by group status. Smoking was strongly related to craving, positive and negative affect, PTSD symptoms, restlessness, and several situational variables among PTSD smokers. For non-PTSD smokers, the only significant antecedent variables for smoking were craving, drinking coffee, being alone, not being with family, not working, and being around others who were smoking. These results are consistent with previous ambulatory findings regarding mood in smokers but also underscore that, in certain populations, mood and symptom variables may be significantly associated with ad lib smoking.     

Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers

Objective

The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers.

Method

AD (n = 119) and control (n = 55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N = 34) and control (N = 19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B).

Results

Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS.

Conclusions

Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD.     

Corticotropin-releasing factor potentiates acoustic startle in rats: Blockade by chlordiazepoxide

A series of experiments was performed to investigate the effects of corticotropin-releasing factor (CRF) on the amplitude of the acoustic startle response (ASR) in rats. Intracerebroventricular (ICV) administration of 1 g rat CRF significantly potentiated acoustic startle amplitude; these effects were reversed in a dose-dependent manner by pretreatment with the benzodiazepine chlordiazepoxide (CDP). Doses of CDP that anatgonized CRF-potentiated ASR did not lower startle baseline or antagonize amphetamine-or strychnine-potentiated ASR. These results suggest that CRF has anxiogenic properties and may serve as a neuroendocrine modulator of stress-enhanced behaviors.     

Cigarette smoking, ambulatory cardiovascular monitoring, and mood in Vietnam veterans with and without chronic posttraumatic stress disorder

This study investigated the association among cigarette smoking, posttraumatic stress disorder (PTSD), and ambulatory cardiovascular and mood monitoring in 117 male Vietnam combat veterans (61 with PTSD and 56 without PTSD). Positive smoking status was associated with higher systolic blood pressure (SBP) and heart rate (HR), as well as greater diastolic blood pressure (DBP) variability. Compared to individuals without PTSD, PTSD patients had higher HR, anger/hostility ratings, and depression/anxiety ratings. Significant diagnosis by smoking status interactions were found indicating that compared to nonsmokers with PTSD, smokers with PTSD had higher DBP, mean arterial pressure (MAP), and positive affect. Ad lib cigarette smoking during the previous 30 min did not have a significant effect on mood or cardiovascular parameters, except in non-PTSD smokers who reported lower depression/anxiety ratings after smoking. Findings suggest that the effect of smoking on cardiovascular parameters may be amplified in smokers in PTSD. Findings suggest that the interrelationships among cardiovascular parameters, cigarette smoking, and PTSD deserve more research attention.     

Alprazolam treatment immediately after stress exposure interferes with the normal HPA-stress response and increases vulnerability to subsequent stress in an animal model of PTSD

BackgroundIn light of clinical reports suggesting that early benzodiazepine administration interferes with long-term recovery from traumatic stress, a prospective animal model for PTSD was employed to assess the short- and long-term effects of a brief course of alprazolam following stress exposure. Method: Animals exposed to stress were treated either 1 h or 7 days later with alprazolam or vehicle for 3-days. Outcome measures included behavior in the elevated plus-maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. One group was repeatedly exposed to the triggering trauma shortly before and after treatment and assessed as above. Circulating corticosterone levels were assessed 4 h after initiation of alprazolam and post-treatment. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into ‘extreme’, ‘minimal,’ or ‘partial’ behavioral response for analysis of prevalence rates. Results: Immediate alprazolam treatment was effective in alleviating anxiety at day 4. No observable anxiolytic effects remained at day 30. Immediate alprazolam also resulted in significantly greater freezing response to trauma-cue exposure and in extreme responses to double-exposure. Corticosterone levels were significantly suppressed by alprazolam during treatment and rebounded after cessation. Conclusion: A brief course of alprazolam in the immediate aftermath of stress-exposure is associated with less favorable responses to additional stress-exposure later on. Alprazolam was associated with a significant attenuation of the HPA-response, suggesting a possible link between initial HPA-axis response disruption and the subsequent unfavorable outcomes.     

Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder

Preclinical and clinical studies have suggested that the acoustic startle reflex (ASR) is a useful model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals and in healthy human controls. Because of the growing body of data that support the hypothesis that severe stress results in substantial alterations in noradrenergic neuronal reactivity, the present investigation evaluated the effects of yohimbine on the ASR of 18 patients with PTSD and 11 healthy combat controls. Subjects received IV yohimbine (0.4 mg/kg) or saline placebo on 2 separate days in a randomized double blind placebo control design. A trial of two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise and instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25–60 s, for a 40-ms duration. Startle testing was performed 80 min post-infusion and lasted 15–20 min. Yohimbine significantly increased the amplitude, magnitude and probability of the ASR in combat veterans with PTSD, but did not do so in combat controls. Overall startle was significantly larger in the PTSD subjects; however, this did not account for the differential effect of yohimbine, since yohimbine had no significant effect in the control group. This study demonstrates an excitatory effect of yohimbine on the amplitude, magnitude and probability of the ASR in PTSD patients that is not seen in combat controls. In the context of the key role of this reflex in the alarm response, this finding adds to the array of documented behavioral, biochemical and cardiovascular effects of yohimbine in humans which support the relationship between increased noradrenergic function and exaggerated startle symptomatology of PTSD.     

Nicotine differentially inhibits the acoustic startle reflex in African American and Caucasian American smokers

Research suggests that there are racial disparities in smoking behaviors, cessation rates, mortality, and morbidity. However, little is known regarding racial differences in affect regulation by smoking. The purpose of this study was to examine racial differences in the effects of nicotine deprivation and administration on smokers' startle responding to smoking and affective cues. 104 African American (AA) and Caucasian American (CA) smokers completed 4 laboratory sessions crossing nicotine deprivation (12-hour deprived vs. nondeprived) with nicotine nasal spray (active vs. placebo). Participants viewed affective (positive, neutral, and negative) and smoking slides while startle probes were administered. The results showed that relative to placebo, AA smokers given nicotine spray exhibited significantly lower startle responses when they were exposed to smoking cues and CA smokers given nicotine spray exhibited significantly lower startle responses when they were exposed to negative and neutral cues. Although nicotine suppresses startle responding in both AA and CA smokers, the effect is modulated by different cue conditions, suggesting that there may be racial differences in components of smoking motivation.     

Effects of smoking cessation, acute re-exposure and nicotine replacement in smokers on AIR inhaled insulin pharmacokinetics and glucodynamics

Aims

To explore the effects of smoking cessation and acute smoking re-exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR® inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT).

Methods

Nondiabetic smokers (n = 24) with normal pulmonary function completed a two-phase (four-period), open-label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8–12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4-week smoking-cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re-exposure on inhaled insulin PK and GD.

Results

Compared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4-week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced.

Conclusion

Smoking, smoking cessation and acute re-exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism.

What is already known about this subject

• Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the risk for hypoglycaemia and thus should not be used by active smokers.

What this study adds

• This is the first euglycaemic clamp study on the impact of smoking cessation, acute smoking re-exposure and nicotine replacement on AIR® inhaled insulin pharmacokinetics and glucodynamics.
• We demonstrate clinically and statistically significant shifts in glucodynamic response to acute re-exposure to a single cigarette, leading us to conclude that active smokers should be advised against inhaled insulin therapy until smoking abstinence is stable.
• Additionally, these results are also the first to demonstrate an apparent independent effect of nicotine replacement therapy on insulin exposure and glucodynamic response.

     

Does the exposure to smoking cues in movies affect adolescents' immediate smoking behavior?

Introduction

Various studies have demonstrated that environmental smoking cues elicit smoking-related responses in smokers. However, cue reactivity studies among adolescent smokers are scarce. Therefore, the aim of this study was to examine the effect of smoking portrayal in movies on immediate smoking behavior in adolescent smokers.

Method

A total of 65 adolescent daily smokers (between the ages of 16 and 18 years) were exposed to a one-hour movie clip, with or without smoking characters, and were allowed to smoke while watching the movie.

Results

The exposure to smoking cues in movies had no effect on immediate smoking behavior. This association was not affected by several smoking- and movie-related variables.

Conclusions

No influence of smoking cues in movies on immediate smoking behavior in adolescent daily smokers was found. More experimental research on the effects of environmental cues on adolescent smokers in different stages of addiction is needed.     

Cigarette smoking and white matter microstructure

Rationale  

Diffusion tensor imaging has been used before in testing associations between cigarette smoking and white matter integrity, with inconsistent results. Published reports indicate higher fractional anisotropy (FA, a measure of linear water diffusion) in some brain regions and lower FA in others in adult smokers compared to nonsmokers. Adolescent smokers exhibited elevated FA at several brain regions and a positive correlation of FA in the genu corpus callosum with exposure to smoking (pack-years).