Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.

OBJECTIVES: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke. METHODS: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression. RESULTS: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant. CONCLUSIONS: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

Randomized Controlled Trial of Aerobic Exercise for Smoking Cessation among Individuals with Elevated Depressive Symptoms.

INTRODUCTION: Adults with depression have higher rates of cigarette smoking and are more likely to relapse than those without depression. Pharmacological, psychological, and combined interventions have largely yielded small improvements in smoking outcomes for adults with depression. Aerobic exercise (AE) may facilitate smoking cessation in this subpopulation. METHODS: This study was a 12-week two-arm randomized controlled trial that evaluated the effect of a moderate-intensity AE program compared to a health education contact (HEC) control on smoking cessation in adults with elevated depressive symptoms (mild to severe). Participants (n=231) were randomized to AE or HEC and received smoking cessation treatment (telephone counseling and nicotine replacement therapy). Primary (biologically confirmed 7-day point prevalence abstinence) and secondary (depressive symptoms, objective and self-reported physical activity, and cardiorespiratory fitness) outcomes were assessed at baseline, 3-, 6-, and 12-months. Data were analyzed with mixed-effects generalized linear models controlling for age, gender, nicotine dependence, history of major depression disorder, and month of follow-up assessment. RESULTS: There were no significant differences in primary or secondary outcomes between the AE and HEC groups. CONCLUSIONS: The AE program was not superior to HEC in facilitating smoking cessation, increases in physical activity, or improved depressive symptoms. Given evidence for the positive acute effects of exercise on mood and smoking urges, future research should consider testing alternative exercise approaches for aiding smoking cessation beyond structured, aerobic exercise programs. IMPLICATIONS: This study found that an adjunctive aerobic exercise (AE) program was not superior to a health education contact control for adults with elevated depressive symptoms, all of whom also received standard smoking cessation treatment. This finding adds to the growing body of literature that structured aerobic exercise programs for smoking cessation may have limited efficacy for cessation outcomes. Future research is needed to test alternative methods of integrating AE into smoking cessation treatment, such as strategically using exercise to manage cravings and low mood in the moment.

An examination of the effects of distress intolerance and rating of perceived exertion on changes in mood and anxiety following aerobic exercise among treatment-seeking smokers.

Aerobic exercise is frequently used as an intervention for depression and smoking cessation because of its antidepressant and anxiolytic effects. Distress intolerance (DI) is a proposed individual difference factor that, coupled with a higher rating of perceived exertion during exercise, may significantly impact the acute mood and anxiolytic effects of exercise. The current study examined the interactive effect of maximum rating of perceived exertion (RPE) and DI on change in mood and anxiety. Treatment-seeking smokers (Mage = 45.32; 72% female) with elevated depressive symptoms completed a 1-mile treadmill walk at their preferred intensity and self-reported their RPE during the test. Analyses were conducted to examine whether there was an interactive effect of maximum RPE and DI on change in self-reported mood and anxiety from before to after the walk test. Findings indicate a significant moderating effect of RPE at lower ratings. Individuals reporting a low maximum RPE and higher DI exhibit a greater change in mood over the course of an exercise session, whereas individuals reporting a low maximum RPE and a lower DI exhibit smaller changes in mood. These results indicate that the subjective effects of exercise within a population of cigarette smokers could be improved by tailoring exercise intensity to individual characteristics. Mild to moderate-intensity exercise, as compared to high-intensity exercise, may result in greater changes in mood for individuals endorsing difficulty tolerating affective and physical distress.

Stakeholder perspectives on adjunctive mHealth services during transitions of care for patients with schizophrenia-spectrum disorders.

BACKGROUND: A growing body of research focuses on developing and testing interventions that leverage mental health-related mobile health (mHealth) services for patients with schizophrenia and other schizophrenia-spectrum disorders. Yet, most formative research has focused on patient perspectives, with little attention paid to clinical stakeholders. AIMS: This qualitative study aimed to explore clinical stakeholders' (i.e., administrative supervisors, support staff, and clinicians) perspectives on what might help or hinder the use of mHealth, particularly when patients transition from inpatient to outpatient care. METHODS: In-depth individual qualitative interviews were conducted with 18 stakeholders from inpatient and outpatient psychiatric settings. RESULTS: Four key themes were identified: (a) adherence challenges; (b) role of mobile technology in patient care; (c) clinical professionals' receptiveness to adjunctive mHealth services; and, (d) costs related to implementation of mHealth services. CONCLUSIONS: Overall, stakeholders agree with extant data showing that supportive networks are important in facilitating patients' return to the community following hospitalization. Stakeholders welcome mHealth services but suggest they should be appropriately tailored to the population, both in terms of usability and connection to ongoing traditional treatments. Demonstration of added value will likely facilitate wider implementation of mHealth services in the care of patients with schizophrenia and other schizophrenia-spectrum disorders.

Readiness to Quit Smoking among Smokers in Substance Use Treatment: Associations with Stress, Substance Use Severity, Relapse Concerns and Gender.

Smoking prevalence among individuals in substance use treatment remains higher than in the general population. Given that many smokers in substance use treatment are reluctant to quit smoking, it is important to understand the factors that impede smokers' readiness to quit. The current study used baseline data from a randomized controlled trial involving 60 adult smokers receiving substance use treatment to investigate relations between the severity of substance use problems (SSUP), perceived stress (PS), concerns about relapse (i.e., concerns that quitting smoking would hurt one's recovery process (CR)), and readiness to quit smoking. This study also investigated moderating roles of concerns about relapse and gender. Regression analyses showed a significant main effect of concerns about relapse on readiness to quit in the next 30 days, but no effect for either severity of substance use problems, perceived stress, or the SSUPxCR interaction. There were significant interaction effects between PS and both gender and CR. Among men and those with lower concerns about relapse, higher perceived stress was significantly associated with lower readiness to quit. Findings suggest that psychoeducation to alleviate concerns that quitting smoking could limit substance use recovery could be beneficial. Stress management interventions may be especially beneficial to men.

Anxiety sensitivity and daily cigarette smoking in relation to sleep disturbances in treatment-seeking smokers.

Although the association between anxiety and sleep disturbance is well-documented, the underlying mechanisms are less clear. Anxiety sensitivity (AS), the fear of physiological arousal and bodily sensations, is a risk factor for anxiety and poor sleep. Smoking also contributes to poor sleep and may compound the effects of AS on sleep quality. This study evaluated the main and interactive effects of AS and cigarettes/day on sleep quality among smokers. Participants (n = 190) were adult treatment-seeking daily smokers who completed a baseline assessment as part of a larger smoking cessation trial. Sleep quality was self-reported. Results indicated that AS was significantly correlated with greater disturbance in sleep duration, subjective sleep quality, sleep onset latency, sleep disturbance, daytime dysfunction, and sleep medication use. There was a significant interaction between AS and cigarettes/day in terms of sleep onset latency, but not other sleep quality indices. AS was associated with significantly longer sleep onset latency minutes among heavier smokers, but not lighter smokers. Specifically, the association between AS and sleep onset latency was significant for those who smoked ≥ 33 cigarettes/day. AS is a psychological factor that may contribute to poor sleep quality, especially in heavy smokers, and thus may be a promising intervention target.

Effects of Negative Affect, Urge to Smoke, and Working Memory Performance (n-back) on Nicotine Dependence.

BACKGROUND: Three key domains including negative emotionality, incentive salience, and executive function form the core functional elements of addictive behaviors. Variables related to these broader domains have been studied extensively in relation to one another; however, no studies to date, have examined models including variables from all three domains, in relation to nicotine dependence. METHOD: Smokers (N = 117), 65.8% female, 78% white, mean age of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures of negative affect (a component of negative emotionality), urge to smoke (incentive salience), and working memory (WM; a core executive function), during a baseline assessment period prior to initiating treatment. RESULTS: Negative affect was associated with greater urge to smoke, and this elevated urge to smoke was associated with higher levels of nicotine dependence. Further, a significant moderated mediation indicated that WM moderated the relationship between increased urge to smoke and nicotine dependence. For those with low to average WM, urge to smoke was significantly related to nicotine dependence; however, for those with higher WM (+1 SD), urge to smoke stemming from negative affect was not associated with nicotine dependence. CONCLUSIONS: To our knowledge, this is the first reported relationship between negative affect, urge to smoke, WM, and nicotine dependence. Although preliminary, results indicate that WM may moderate the relationship between urge to smoke associated with negative affect and nicotine dependence. Treatments targeting WM may be particularly useful for individuals with average to low WM who experience urge to smoke related to negative affect.

Development and preliminary pilot evaluation of a brief tablet computer intervention to motivate tobacco quitline use among smokers in substance use treatment.

BACKGROUND AND OBJECTIVES: The majority of individuals in substance use disorder (SUD) treatment also smoke cigarettes; yet, the availability of smoking cessation services in SUD treatment remains limited. In this study, we developed and piloted a brief intervention for smokers in SUD treatment intended to motivate engagement in tobacco quitline treatment (TIME-TQ). METHODS: First, we interviewed 19 smokers in SUD treatment to inform the development of TIME-TQ (Phase 1). Second, we delivered a prototype TIME-TQ to 16 smokers in the same SUD treatment program and followed them for 3 months post-discharge (Phase 2). RESULTS: Feedback from Phase 1 participants was used to refine response choices and video segments included in the prototype TIME-TQ. Phase 2 participants rated TIME-TQ high on relevance, interest, respectfulness, and helpfulness. Additionally, they reported significant increases in readiness to quit and perceived importance of quitting after receiving TIME-TQ. A total of 8 of the 16 accepted a quitline referral, and 8 of 13 reached for follow-up (four referral acceptors, four decliners) reported efforts to quit or reduce smoking during the follow-up period. However, only three received quitline counseling and none achieved a sustained period of abstinence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our results suggest that TIME-TQ activated these patients to quit smoking, but our referral method (standard fax referral) was unsuccessful in helping participants fully engage in quitline treatment or achieving a period of abstinence. SCIENTIFIC SIGNIFICANCE: We are now conducting an RCT to evaluate TIME-TQ with a revised referral procedure intended to increase treatment engagement and, ultimately, abstinence rates. (Am J Addict 2017;26:587-594).

Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk test among treatment-seeking smokers.

Smoking increases risk of early morbidity and mortality, and risk is compounded by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive factor that may amplify the subjective experience of exertion (effort) during exercise, subsequently resulting in lower engagement in physical activity. We examined the effect of anxiety sensitivity on ratings of perceived exertion (RPE) and physiological arousal (heart rate) during a bout of exercise among low-active treatment-seeking smokers. Adult daily smokers (n = 157; M age  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile submaximal treadmill walk test. RPE and heart rate were assessed during the walk test. Multi-level modeling was used to examine the interactive effect of anxiety sensitivity × time on RPE and on heart rate at five time points during the walk test. There were significant linear and cubic time × anxiety sensitivity effects for RPE. High anxiety sensitivity was associated with greater initial increases in RPE during the walk test, with stabilized ratings towards the last 5 min, whereas low anxiety sensitivity was associated with lower initial increase in RPE which stabilized more quickly. The linear time × anxiety sensitivity effect for heart rate was not significant. Anxiety sensitivity is associated with increasing RPE during moderate-intensity exercise. Persistently rising RPE observed for smokers with high anxiety sensitivity may contribute to the negative experience of exercise, resulting in early termination of bouts of prolonged activity and/or decreased likelihood of future engagement in physical activity.

Telomeres, early-life stress and mental illness.

Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying stress-response biomarker that crosses the brain/body distinction that is often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine for the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

Efficacy of sequential use of fluoxetine for smoking cessation in elevated depressive symptom smokers.

INTRODUCTION: Fluoxetine, a selective serotonin reuptake inhibitor, was examined in the treatment of smokers with elevated depressive symptoms. Specifically, this randomized, open-label clinical trial was designed to evaluate the efficacy of three logical, real-world alternatives for providing smoking cessation treatment to smokers with elevated depressive symptoms. METHODS: In a sample of 216 smokers (mean Center for Epidemiological Studies Depression Scale score = 11.41), participants were randomly assigned to (a) transdermal nicotine patch (TNP), beginning on quit date and continuing for 8 weeks thereafter; (b) standard administration of antidepressant pharmacotherapy with fluoxetine (20mg), beginning 2 weeks before quit date and continuing for 8 weeks following quit date + TNP (ST-FLUOX); or (c) sequential administration of fluoxetine (20mg), beginning 8 weeks before quit date and continuing for 8 weeks following quit date + TNP (SEQ-FLUOX). All participants received 5 sessions of brief behavioral smoking cessation treatment. RESULTS: Findings indicate that SEQ-FLUOX resulted in significantly higher point prevalence abstinence than ST-FLUOX at 6-month follow-up (OR = 2.35; 95% CI = 1.10-5.02, p < .03), a difference that was reduced at the 12-month assessment. Furthermore, sequential fluoxetine treatment, compared with standard fluoxetine treatment, resulted in significantly lower levels of depressive symptoms throughout smoking cessation treatment (p < .025) and significantly lower nicotine withdrawal-related negative affect (p < .004) immediately after quitting. CONCLUSIONS: Findings suggest that if one is going to prescribe fluoxetine for smoking cessation in smokers with elevated depressive symptoms, it is best to begin prescribing fluoxetine well before the target quit date.

Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers.

Evidence now implicates inflammatory proteins in the neurobiology of internalizing disorders. Genetic factors may influence individual responses to maltreatment; however, little work has examined inflammatory genetic variants in adults and none in children. The present study examined the role of an interleukin 1B gene (IL1B) variant in preschoolers exposed to maltreatment and other forms of adversity in internalizing symptom development. One hundred ninety-eight families were enrolled, with one child (age 3-5 years) from each family. Adversity measures included child protective service documentation of moderate-severe maltreatment in the last 6 months and interview-assessed contextual stressors. Internalizing symptoms were measured using the Child Behavior Checklist and the Diagnostic Infant and Preschool Assessment. Maltreated children had higher major depressive disorder (MDD) and posttraumatic stress disorder symptoms and marginally higher internalizing symptoms on the Child Behavior Checklist. Controlling for age, sex, and race, IL1B genotype was associated with MDD symptoms (p = .002). Contextual stressors were significantly associated with MDD and posttraumatic stress disorder and marginally with internalizing symptoms. The IL1B genotype interacted with contextual stress such that children homozygous for the minor allele had more MDD symptoms (p = .045). These results suggest that genetic variants of IL1B may modulate the development of internalizing symptoms in the face of childhood adversity.

Modeling the antidepressant treatment response to transcranial magnetic stimulation using an exponential decay function.

Recovery from depression often demonstrates a nonlinear pattern of treatment response, where the largest reduction in symptoms is observed early followed by smaller improvements. This study investigated whether this exponential pattern could model the antidepressant response to repetitive transcranial magnetic stimulation (TMS). Symptom ratings from 97 patients treated with TMS for depression were collected at baseline and after every five sessions. A nonlinear mixed-effects model was constructed using an exponential decay function. This model was also applied to group-level data from several published clinical trials of TMS for treatment-resistant depression. These nonlinear models were compared to corresponding linear models. In our clinical sample, response to TMS was well modeled with the exponential decay function, yielding significant estimates for all parameters and demonstrating superior fit compared to a linear model. Similarly, when applied to multiple studies comparing TMS modalities as well as to previously identified treatment response trajectories, the exponential decay models yielded consistently better fits compared to linear models. These results demonstrate that the antidepressant response to TMS follows a nonlinear pattern of improvement that is well modeled with an exponential decay function. This modeling offers a simple and useful framework to inform clinical decisions and future studies.

Corrigendum to "Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms" [Brain Behav. Immun. - Health 25 (2022) 100519].

[This corrects the article DOI: 10.1016/j.bbih.2022.100519.].

The role of avoidance in the phenomenology of obsessive-compulsive disorder.

BACKGROUND: Pathologic levels of ritualistic avoidance (also known as active avoidance) are common in the clinical presentation of obsessive-compulsive disorder (OCD). Despite its clinical relevance, there has been little examination of active avoidance as a ritualistic compulsion in adults with OCD. OBJECTIVE: The objective of this study is to determine if adults with OCD who engage in ritualistic avoidance have greater obsessive-compulsive, anxiety, and depressive symptom severity and different comorbidity patterns than adults who do not engage in ritualistic avoidance. METHOD: Adults with OCD (n = 133) completed an evaluation that included clinician ratings of obsessive-compulsive severity; overall illness severity; and self-reported ratings of anxiety, depression, and obsessive-compulsive severity. RESULTS: Ritualized avoidance was endorsed by greater than 25% of the sample. Avoidant subjects and, more specifically, contaminant avoidant and reading-writing avoidant subjects presented with elevated levels of obsessive-compulsive symptom severity and greater overall clinical severity than comparison patients who did not engage in each respective avoidance ritual. CONCLUSIONS: Patients who engage in ritualized avoidance exhibited greater obsessive-compulsive symptom severity than patients who did not. These findings suggest that ritualized avoidance functions as a compulsion for adults with OCD and that avoidance should receive careful consideration in assessment and treatment.

The nicotinic acetylcholine receptor as a target for antidepressant drug development.

An important new area of antidepressant drug development involves targeting the nicotinic acetylcholine receptor (nAChR). This receptor, which is distributed widely in regions of the brain associated with depression, is also implicated in other important processes that are relevant to depression, such as stress and inflammation. The two classes of drugs that target nAChRs can be broadly divided into mecamylamine- and cytisine-based compounds. These drugs probably exert their effects via antagonism at α4ß2 nAChRs, and strong preclinical data support the antidepressant efficacy of both classes when used in conjunction with other primary antidepressants (e.g., monoamine reuptake inhibitors). Although clinical data remain limited, preliminary results in this area constitute a compelling argument for further evaluation of the nAChR as a target for future antidepressant drug development.

Examining the effect of exercise on the relationship between affect and cravings among smokers engaged in cessation treatment.

Cigarette smoking is associated with multiple adverse health outcomes. When smokers attempt to quit smoking, one of the leading predictors of relapse are cravings. Recent research shows a relationship between positive and negative affect, exercise, and cravings, but the exact nature of this relationship has yet to be understood. This study explored the relationships between positive and negative affect and cravings in a sample of participants with elevated levels of depressive symptoms (N = 202; 68.8% female; mean age = 46.1 years) who were enrolled in a smoking cessation trial to test the efficacy of a 12-week exercise intervention relative to a health education control on smoking outcomes. Data on affect and craving were gathered before weekly study intervention sessions, and data on cravings were gathered again after each session. The results showed that negative affect had a significant and positive association with cravings before an exercise or health education session. After the session, positive and negative affect were not significant predictors of changes in cravings from pre-session. However, regardless of level of positive or negative affect participants in the exercise condition showed greater reductions in craving pre- to post-class than those in the control condition. These findings suggest that negative affect is associated with cravings, but cravings can be mitigated by exercise.

Associations of circulating cell-free DNA, C-reactive protein, and cardiometabolic risk among low-active smokers with elevated depressive symptoms.

Background and aims: Cell-free DNA (cfDNA) is elevated in several disease states. Metabolic syndrome is a constellation of factors associated with poor cardiometabolic outcomes. This study examined associations of cfDNA from the nucleus (cf-nDNA) and mitochondria (cf-mtDNA), C-reactive protein (CRP), and metabolic syndrome risk, in low-active smokers with depressive symptoms. Methods: Participants (N = 109; mean age 47) self-reported medical history. Physical activity was determined by accelerometry and anthropometrics were measured. Blood was collected and analyzed for cf-nDNA, cf-mtDNA, CRP, triglycerides, high-density lipoprotein, hemoglobin A1c. A continuous metabolic syndrome composite risk score was calculated. Relationships of cf-nDNA, cf-mtDNA, CRP, and cardiometabolic risk were examined with correlations and linear regression. Results: CRP and cf-nDNA were significantly associated with metabolic syndrome risk (r = .39 and r = .31, respectively), cf-mtDNA was not (r = .01). In a linear regression, CRP and cf-nDNA significantly predicted the metabolic syndrome risk score, findings that remained significant controlling for age, gender, nicotine dependence, and physical activity. Conclusions: Associations of cf-nDNA with both CRP and metabolic risk suggest a role for cf-nDNA in inflammatory processes associated with metabolic syndrome. The negative findings for cf-mtDNA suggest distinct roles for cf-nDNA and cf-mtDNA in these processes.

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking. METHOD: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, n = 25) or enhanced standard treatment (EST, n = 24) with noncontingent rewards. Participants in SMI-CM were prompted to practice audio-guided mindfulness five times per day for 38 days (vs. no comparison intervention in EST), and received monetary incentives for carbon monoxide (CO) ≤ 6 ppm. The primary outcome was biochemically verified 7-day point prevalence abstinence rates 2, 4, and 13 weeks after a target quit day. RESULTS: Of the 49 participants, 63.3% were Latinx and 30.6% Black; 75.5% reported household incomes < $25,000. Abstinence rates for SMI-CM were 40.0%, 36.0%, and 16.0% versus 4.2%, 8.3%, and 4.2% in EST at weeks 2, 4, and 13. A generalized estimating equations (GEE) model showed significant overall differences in abstinence rates in SMI-CM versus EST (adjusted odds ratio [AOR] = 8.12, 95% CI = 1.42-46.6, p = .019). Those who received SMI-CM reported significantly greater reduction in smoking-specific experiential avoidance from baseline to 3 days prior to quit date (ß = -7.21, 95% CI = -12.1-2.33, p = .006). CONCLUSIONS: SMI-CM may increase cessation rates among smokers with mood disorders, potentially through reduced smoking-specific experiential avoidance. SMI-CM is a promising intervention, and warrants investigation in a fully powered randomized controlled trial (RCT). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Variation in NGFB is associated with primary affective disorders in women.

Affective disorders (AFDs) are highly comorbid with substance dependence (SD) and both are genetically influenced. However, the specific etiology of the comorbidity is not well understood. We genotyped an array of 1,350 single nucleotide polymorphisms (SNPs) in or near 130 genes in 868 European-Americans (EAs), including 182 individuals with primary AFDs (PAFDs), 214 with SD comorbid with AFD (CAFD), and 472 screened controls. NGFB, which encodes nerve growth factor ß and was represented in the array by 15 SNPs, showed the strongest evidence of association, but only among women with PAFDs. Six of the SNPs showed nominally significant association with PAFDs in women (P's = 0.0007-0.01); three (rs2856813, rs4332358, and rs10776799) were empirically significant based on 1,000,000 permutations (P's = 0.008-0.015). Seven haplotypes were significantly associated with PAFDs in women (P's = 0.0014-0.01), of which six were significant based on empirical permutation analysis (minimal P = 0.0045). Four diplotypes were significantly associated with PAFDs in women (global P's = 0.001-0.01). The specific diplotype GG-TC, reconstructed from rs2856813 and rs6678788, showed the strongest evidence of association with PAFDs in women (OR = 4.07, P = 4.2E-05). No SNPs or haplotypes were associated with PAFDs in men or with CAFDs in either sex. We conclude that variation in NGFB is a risk factor for PAFDs in women, but not for CAFD.