The influences of stomatal size and density on rice abiotic stress resilience.

A warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice (Oryza sativa) yields. Elevated temperatures combined with vapour pressure deficit (VPD) rises are causing stomatal closure, further reducing plant productivity and cooling. It is unclear what stomatal size (SS) and stomatal density (SD) will best suit all these environmental extremes. To understand how stomatal differences contribute to rice abiotic stress resilience, we screened the stomatal characteristics of 72 traditionally bred varieties. We found significant variation in SS, SD and calculated anatomical maximal stomatal conductance (gsmax ) but did not identify any varieties with SD and gsmax as low as transgenic OsEPF1oe plants. Traditionally bred varieties with high SD and small SS (resulting in higher gsmax ) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties assessed were as resilient to drought or salinity as low SD OsEPF1oe transgenic plants. High SD and small SS rice displayed faster stomatal closure during increasing temperature and VPD, but photosynthesis and plant cooling were reduced. Compromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses.

The influence of stomatal morphology and distribution on photosynthetic gas exchange.

The intricate and interconnecting reactions of C3 photosynthesis are often limited by one of two fundamental processes: the conversion of solar energy into chemical energy, or the diffusion of CO2 from the atmosphere through the stomata, and ultimately into the chloroplast. In this review, we explore how the contributions of stomatal morphology and distribution can affect photosynthesis, through changes in gaseous exchange. The factors driving this relationship are considered, and recent results from studies investigating the effects of stomatal shape, size, density and patterning on photosynthesis are discussed. We suggest that the interplay between stomatal gaseous exchange and photosynthesis is complex, and that a disconnect often exists between the rates of CO2 diffusion and photosynthetic carbon fixation. The mechanisms that allow for substantial reductions in maximum stomatal conductance without affecting photosynthesis are highly dependent on environmental factors, such as light intensity, and could be exploited to improve crop performance.

Rice with reduced stomatal density conserves water and has improved drought tolerance under future climate conditions.

Much of humanity relies on rice (Oryza sativa) as a food source, but cultivation is water intensive and the crop is vulnerable to drought and high temperatures. Under climate change, periods of reduced water availability and high temperature are expected to become more frequent, leading to detrimental effects on rice yields. We engineered the high-yielding rice cultivar 'IR64' to produce fewer stomata by manipulating the level of a developmental signal. We overexpressed the rice epidermal patterning factor OsEPF1, creating plants with substantially reduced stomatal density and correspondingly low stomatal conductance. Low stomatal density rice lines were more able to conserve water, using c. 60% of the normal amount between weeks 4 and 5 post germination. When grown at elevated atmospheric CO2 , rice plants with low stomatal density were able to maintain their stomatal conductance and survive drought and high temperature (40°C) for longer than control plants. Low stomatal density rice gave equivalent or even improved yields, despite a reduced rate of photosynthesis in some conditions. Rice plants with fewer stomata are drought tolerant and more conservative in their water use, and they should perform better in the future when climate change is expected to threaten food security.

Molecular control of stomatal development.

Plants have evolved developmental plasticity which allows the up- or down-regulation of photosynthetic and water loss capacities as new leaves emerge. This developmental plasticity enables plants to maximise fitness and to survive under differing environments. Stomata play a pivotal role in this adaptive process. These microscopic pores in the epidermis of leaves control gas exchange between the plant and its surrounding environment. Stomatal development involves regulated cell fate decisions that ensure optimal stomatal density and spacing, enabling efficient gas exchange. The cellular patterning process is regulated by a complex signalling pathway involving extracellular ligand-receptor interactions, which, in turn, modulate the activity of three master transcription factors essential for the formation of stomata. Here, we review the current understanding of the biochemical interactions between the epidermal patterning factor ligands and the ERECTA family of leucine-rich repeat receptor kinases. We discuss how this leads to activation of a kinase cascade, regulation of the bHLH transcription factor SPEECHLESS and its relatives, and ultimately alters stomatal production.

Longitudinal associations between smoking cessation medications and alcohol consumption among smokers in the International Tobacco Control Four Country survey.

BACKGROUND: Available evidence suggests that quitting smoking does not alter alcohol consumption. However, smoking cessation medications may have a direct impact on alcohol consumption independent of any effects on smoking cessation. Using an international longitudinal epidemiological sample of smokers, we evaluated whether smoking cessation medications altered alcohol consumption independent of quitting smoking. METHODS: Longitudinal data were analyzed from the International Tobacco Control Four Country (ITC-4) Survey between 2007 and 2008, a telephone survey of nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States (n = 4,995). Quantity and frequency of alcohol consumption, use of smoking cessation medications (varenicline, nicotine replacement [NRT], and no medications), and smoking behavior were assessed across 2 yearly waves. Controlling for baseline drinking and changes in smoking status, we evaluated whether smoking cessation medications were associated with reduced alcohol consumption. RESULTS: Varenicline was associated with a reduced likelihood of any drinking compared with nicotine replacement (OR = 0.56; 95% CI = 0.34 to 0.94), and consuming alcohol once a month or more compared to nicotine replacement (OR = 0.43; 95% CI = 0.27 to 0.69) or no medication (OR = 0.63; 95% CI = 0.41 to 0.99). Nicotine replacement was associated with an increased likelihood of consuming alcohol once a month or more compared to no medication (OR = 1.14; 95% CI = 1.03 to 1.25). Smoking cessation medications were not associated with more frequent drinking (once a week or more) or typical quantity consumed per episode. Medication effects on drinking frequency were independent of smoking cessation. CONCLUSIONS: This epidemiological investigation demonstrated that varenicline was associated with a reduced frequency of alcohol consumption. Continued work should clarify under what conditions nicotine replacement therapies may increase or decrease patterns of alcohol consumption.

A preliminary study on the effect of combined nicotine replacement therapy on alcohol responses and alcohol self-administration.

BACKGROUND AND OBJECTIVES: Limiting alcohol consumption may help prevent alcohol-mediated smoking relapse in heavy drinking smokers. This pilot study examined whether combining a nicotine patch with nicotine nasal spray has stronger attenuating effects on alcohol response and consumption than a nicotine patch alone. METHODS: Twenty-two non-alcohol dependent heavy drinking smokers completed the double-blind cross-over, placebo-controlled study (21 mg nicotine patch + nicotine or placebo nasal spray). Six hours after 21 mg nicotine patch application, subjective and physiological responses to a priming drink (0.3 g/kg) were assessed, followed by two 1-hr alcohol self-administration periods, with possible consumption of up to 4 drinks per period (each 0.15 g/kg). Nasal spray (1 mg [active] or 0 mg [placebo] per dose) was administered 10 min prior to the priming dose and each self-administration period. RESULTS: Active nasal spray did not increase serum nicotine levels, compared with placebo administration. The number of drinks consumed did not differ by the nasal spray conditions. However, positive subjective responses to the priming drink were lower in the active nasal spray condition than the placebo nasal spray condition. During the self-administration period, urge to drink was also lower in the active spray condition than the placebo condition. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Augmenting the nicotine patch with nicotine nasal spray attenuated positive subjective alcohol response and craving and suggests that future studies should investigate whether these findings translate to a clinical setting.

Induced Genetic Variations in Stomatal Density and Size of Rice Strongly Affects Water Use Efficiency and Responses to Drought Stresses.

Rice (Oryza sativa L.) is an important food crop relied upon by billions of people worldwide. However, with increasing pressure from climate change and rapid population growth, cultivation is very water-intensive. Therefore, it is critical to produce rice that is high-yielding and genetically more water-use efficient. Here, using the stabilized fast-neutron mutagenized population of Jao Hom Nin (JHN) - a popular purple rice cultivar - we microscopically examined hundreds of flag leaves to identify four stomatal model mutants with either high density (HD) or low density (LD) stomata, and small-sized (SS) or large-sized (LS) stomata. With similar genetic background and uniformity, the stomatal model mutants were used to understand the role of stomatal variants on physiological responses to abiotic stress. Our results show that SS and HD respond better to increasing CO2 concentration and HD has higher stomatal conductance (gs) compared to the other stomatal model mutants, although the effects on gas exchange or overall plant performance were small under greenhouse conditions. In addition, the results of our drought experiments suggest that LD and SS can better adapt to restricted water conditions, and LD showed higher water use efficiency (WUE) and biomass/plant than other stomatal model mutants under long-term restricted water treatment. Finally, our study suggests that reducing stomata density and size may play a promising role for further work on developing a climate-ready rice variety to adapt to drought and heat stress. We propose that low stomata density and small size have high potential as genetic donors for improving WUE in climate-ready rice.

Rice Stomatal Mega-Papillae Restrict Water Loss and Pathogen Entry.

Rice (Oryza sativa) is a water-intensive crop, and like other plants uses stomata to balance CO2 uptake with water-loss. To identify agronomic traits related to rice stomatal complexes, an anatomical screen of 64 Thai and 100 global rice cultivars was undertaken. Epidermal outgrowths called papillae were identified on the stomatal subsidiary cells of all cultivars. These were also detected on eight other species of the Oryza genus but not on the stomata of any other plant species we surveyed. Our rice screen identified two cultivars that had "mega-papillae" that were so large or abundant that their stomatal pores were partially occluded; Kalubala Vee had extra-large papillae, and Dharia had approximately twice the normal number of papillae. These were most accentuated on the flag leaves, but mega-papillae were also detectable on earlier forming leaves. Energy dispersive X-Ray spectrometry revealed that silicon is the major component of stomatal papillae. We studied the potential function(s) of mega-papillae by assessing gas exchange and pathogen infection rates. Under saturating light conditions, mega-papillae bearing cultivars had reduced stomatal conductance and their stomata were slower to close and re-open, but photosynthetic assimilation was not significantly affected. Assessment of an F3 hybrid population treated with Xanthomonas oryzae pv. oryzicola indicated that subsidiary cell mega-papillae may aid in preventing bacterial leaf streak infection. Our results highlight stomatal mega-papillae as a novel rice trait that influences gas exchange, stomatal dynamics, and defense against stomatal pathogens which we propose could benefit the performance of future rice crops.

Nicotine deprivation and trait impulsivity affect smokers' performance on cognitive tasks of inhibition and attention.

Increased nicotine deprivation and impulsivity have been associated with relapse but the degree to which they together influence cognitive processing has not been explored. We examined the effects of increasing levels of nicotine deprivation on cognitive processing, and assessed the relationship of trait impulsivity with these effects in daily smokers (n=30). Using a within-subject design with three deprivation conditions (nondeprived, 5-hr, 17-hr), volunteers completed the Conners' Continuous Performance Task-II and the Cued Go/No-Go Task. Trait impulsivity was assessed at intake with the Barratt Impulsiveness Scale (Patton et al., 1995). Mixed-model regression analyses revealed deprivation slowed reaction time, increased errors, increased variability in responding, and increased failures of inhibitory control. Performance at 17 hours of deprivation was most likely to be affected. Significant deprivation and impulsivity interactions indicated impulsiveness was negatively correlated with deprivation-associated performance decrements. Less impulsive smokers were more affected by deprivation, demonstrating greater impairment. Research is needed to understand mechanisms by which impulsivity confers greater risk for relapse. Our results suggest deprivation may not increase relapse risk among impulsive smokers by increasing impairment of cognitive processing.

Effects of alcohol on simulated driving and perceived driving impairment in binge drinkers.

BACKGROUND: Binge drinking (heavy episodic alcohol use) is associated with high rates of impaired driving and myriad alcohol-related accidents. However, the underlying reasons for the heightened accident risk in this demographic group are not known. This research examined acute alcohol effects on simulated driving performance and subjective ratings of intoxication and driving ability in binge and nonbinge drinkers. METHODS: Young social drinking college students (24 binge drinkers and 16 nonbinge drinkers) participated in this study. Participants attended a session during which they received a moderate dose of alcohol (0.65 g/kg) and a session during which they received a placebo. A simulated driving task measured participants' driving performance in response to each dose. Subjective responses to each dose were also assessed, including ratings of sedation, stimulation, and driving ability. RESULTS: The acute dose of alcohol impaired multiple aspects of driving performance in both binge and nonbinge drinkers. Under alcohol, all participants had greater difficulty in maintaining their lane position, maintaining the appropriate speed and made multiple driving errors compared to placebo performance. By contrast, compared with nonbinge drinkers, binge drinkers reported feeling less sedated by the alcohol and reported having a greater ability to drive following the acute dose of alcohol. CONCLUSIONS: Reduced subjective intoxication and perceived driving impairment in binge drinkers may account for the greater accident risk in this demographic group. Binge drinkers may lack the internal sedation cue that helps them accurately assess that they are not able to effectively drive a vehicle after drinking.

Nondaily smoking and alcohol use, hazardous drinking, and alcohol diagnoses among young adults: findings from the NESARC.

BACKGROUND: Nondaily smoking and heavy alcohol use are prevalent behaviors among young adults, with nondaily smoking occurring primarily in the context of alcohol use. Although the relationship between drinking and daily smoking has been well characterized in young adults, few epidemiological investigations have investigated the association between nondaily smoking and drinking behavior. METHODS: We examined Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Grant et al., 2003b; n = 43,093). Young adults (aged 18 to 25 years; n = 5,838) were stratified on current smoking behavior (daily, nondaily, and nonsmokers in the past 12 months) and differences in weekly quantity of alcohol use, frequency of alcohol use, frequency of binge drinking behavior, rates of NIAAA-defined hazardous drinking, and rates of DSM-IV alcohol diagnoses were investigated. College student status was examined. RESULTS: Twenty-five percent were current smokers and 7% were smoking on a nondaily basis. Seventy-one percent were current drinkers, 39% reported binge drinking at least once a month, 41% met criteria for hazardous drinking, and 18% had alcohol use disorders. Across all measures of alcohol use, there was a significant effect of smoking status, with daily smokers having greater alcohol use patterns, compared with nondaily smokers, with nonsmokers consuming the least. Nondaily smokers were more likely to report any binge drinking in the past 12 months. However, daily smokers were more likely to report daily binge drinking. With regard to hazardous drinking and alcohol use disorders, nondaily smoking conferred the greatest risk, followed by daily smoking with nonsmoking as the reference group. Multinomial logistic regression demonstrated that the odds of being a hazardous drinker were 16 times greater (95% CI 9.46-26.48) in a nondaily smoker compared with a nonsmoker, whereas the odds for a daily smoker were increased by 7-fold (95% CI 5.54-9.36). A similar pattern of results was demonstrated for DSM-IV alcohol diagnoses. No differences across college student status were observed. CONCLUSIONS: The increased risk of hazardous drinking and alcohol use disorders conferred by nondaily smoking supports the findings that nondaily smoking and drinking are highly concomitant behaviors. Results such as these suggest that interventions disengaging alcohol and cigarette use patterns (e.g., smoking bans in alcohol venues) might serve to limit the occurrence of hazardous drinking among young adults at heightened risk for this behavior.

Acute disinhibiting effects of alcohol as a factor in risky driving behavior.

Automobile crash reports show that up to 40% of fatal crashes in the United States involve alcohol and that younger drivers are over-represented. Alcohol use among young drivers is associated with impulsive and risky driving behaviors, such as speeding, which could contribute to their over-representation in alcohol-related crash statistics. Recent laboratory studies show that alcohol increases impulsive behaviors by impairing the drinker's ability to inhibit inappropriate actions and that this effect can be exacerbated in conflict situations where the expression and inhibition of behavior are equally motivating. The present study tested the hypothesis that this response conflict might also intensify the disruptive effects of alcohol on driving performance. Fourteen subjects performed a simulated driving and a cued go/no-go task that measured their inhibitory control. Conflict was motivated in these tasks by providing equal monetary incentives for slow, careful behavior (e.g., slow driving, inhibiting impulses) and for quick, abrupt behavior (fast driving, disinhibition). Subjects were tested under two alcohol doses (0.65 g/kg and a placebo) that were administered twice: when conflict was present and when conflict was absent. Alcohol interacted with conflict to impair inhibitory control and to increase risky and impaired driving behavior on the drive task. Also, individuals whose inhibitory control was most impaired by alcohol displayed the poorest driving performance under the drug. The study demonstrates potentially serious disruptions to driving performance as a function of alcohol intoxication and response conflict, and points to inhibitory control as an important underlying mechanism.

Young adult non-daily smokers: patterns of alcohol and cigarette use.

Binge drinking and non-daily cigarette smoking are behaviors that are both problematic and prevalent in young adults. Although the relationship between drinking and daily smoking has been well categorized, the intersection between drinking and smoking in non-daily smokers has not been heavily researched. Past 30-day and within-episode patterns of alcohol and cigarette use were collected in young adult non-daily smokers (N=40). Results demonstrated that 79% of smoking occurred on drinking days. Alcohol use was significantly greater on smoking days with the result that drinking to risky binge levels was more likely to occur on a smoking day. Smoking typically occurred after a certain level of alcohol pre-load (2.87 drinks). Together these results confirm that young adult non-daily smokers often concurrently use alcohol and cigarettes. Research is needed to identify possible mechanisms underlying the association between binge drinking and cigarette use in this vulnerable population.

Stomatal development: focusing on the grasses.

The development and patterning of stomata in the plant epidermis has emerged as an ideal system for studying fundamental plant developmental processes. Over the past twenty years most studies of stomata have used the model dicotyledonous plant Arabidopsis thaliana. However, cultivated monocotyledonous grass (or Gramineae) varieties provide the majority of human nutrition, and future research into grass stomata could be of critical importance for improving food security. Recent studies using Brachypodium distachyon, Hordeum vulgare (barley) and Oryza sativa (rice) have led to the identification of the core transcriptional regulators essential for stomatal initiation and progression in grasses, and begun to unravel the role of secretory signaling peptides in controlling stomatal developmental. This review revisits how stomatal developmental unfolds in grasses, and identifies key ontogenetic steps for which knowledge of the underpinning molecular mechanisms remains outstanding.

Driver training conditions affect sensitivity to the impairing effects of alcohol on a simulated driving test [corrected].

Research shows that prior behavioral training in a challenging environment reduces alcohol-induced impairment on simple psychomotor tasks. However, no studies have examined if this relationship generalizes to driving performance. The present study examined simulated driving performance and tested the hypothesis that a challenging training history would protect against the impairing effects of alcohol on driving performance. The challenging training history involved driving in a visually-impoverished environment. Thirty adults were randomly assigned to one of three groups. Two groups were tested under alcohol (0.65 g/kg) after prior experience performing the task under either a visually-impoverished environment or a normal visual environment. The remaining group served as a control and was trained and tested under the visually-impoverished condition environment. Results showed that individuals trained in the impoverished environment displayed sober levels of performance when their performance was subsequently tested under alcohol. By contrast, volunteers trained in a normal environment showed impairment under alcohol. The findings suggest that differences in driving training history can affect a driver's sensitivity to the impairing effects of alcohol.

Effects of varenicline on alcohol cue reactivity in heavy drinkers.

RATIONALE: Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving. OBJECTIVE: The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers. METHODS: As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm. RESULTS: Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect. CONCLUSIONS: Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder.

Transfer of learning to compensate for impairment by alcohol and visual degradation.

RATIONALE: Past research on social drinkers shows that prior experience performing a task in a visually degraded environment results in the reduction of alcohol-induced impairment. It is possible that task experience under alcohol might similarly carry over to reduce impairment from visual degradation. OBJECTIVES: The purpose of this study was to test the symmetry of the transfer of learning between two distinct sources of impairment, visual degradation and alcohol. MATERIALS AND METHODS: Psychomotor impairment was measured by a pursuit rotor tracking task. Forty two participants were randomly assigned to one of six treatment groups. Two groups were tested under alcohol after having prior task experience performing with or without visual degradation. Two groups were tested under visual degradation after having prior task experience performing under active (0.65 g/kg) or inactive (placebo) doses of alcohol. The remaining two groups served as controls that tested the learning effects of repeating each active treatment. RESULTS: Clear evidence for asymmetrical transfer of learning was observed. Prior task experience with visual degradation reduced the impairing effects of alcohol. By contrast, prior task experience under alcohol had no effect on impairment produced by visual degradation. CONCLUSIONS: Evidence for differential transfer of learning to compensate for alcohol- and visual-degradation-induced impairment is of practical interest, given that the two disturbances commonly co-occur outside the laboratory. Reasons for the asymmetry are unclear, and likely involve differences in mechanisms by which each treatment impairs psychomotor function.

Social drinkers underestimate the additive impairing effects of alcohol and visual degradation on behavioral functioning.

RATIONALE: Studies have shown that social drinkers are poor estimators of alcohol-induced impairment. Underestimates of blood alcohol concentration and other indices of intoxication are associated with decisions to perform risky behaviors, such as operating a motor vehicle. It is possible that self-evaluations of impaired functioning under alcohol might be particularly compromised in the presence of other sources of impairment. A common source of impairment that co-occurs with alcohol is visual degradation. OBJECTIVES: The present study compared actual and self-evaluated impairment in response to four conditions (0.65 g/kg alcohol, degradation of task-relevant stimuli, alcohol plus visual degradation, and no-treatment control) to determine whether social drinkers would perceive an increase in impairment from the combined treatments. METHODS: Actual psychomotor impairment was measured in 16 social drinkers (eight men) by a pursuit rotor task and their self-evaluations of this impairment were obtained on a rating scale. RESULTS: Alcohol and visual degradation impaired participants' actual performance to a similar degree and, in combination, the impairing effects were additive. Participants' self-evaluation ratings showed that they underestimated the additive impairment produced by the combination of alcohol and visual degradation. CONCLUSIONS: The findings suggest that social drinkers might be unable to appreciate an increase in behavioral impairment when alcohol is consumed in the context of another impairing influence.

Are bad drivers more impaired by alcohol? Sober driving precision predicts impairment from alcohol in a simulated driving task.

The contribution of driver experience to risk for alcohol-related crashes is based on the tacit assumption that driver experience contributes to driver skill which could mediate the impairing effects of alcohol on driving performance. Surprisingly, few studies of alcohol effects on simulated driving performance have examined the role of driver skill as a mediator of the intensity of alcohol impairment. The present study examined the degree to which individual differences in driving skill mediated the intensity of impairment produced by a moderate dose of alcohol in a group of young adult drivers. Twenty-eight participants were familiarized with a simulated driving road test. After determining their baseline skill level, participants' driving performance was re-tested under either an active dose of alcohol (0.65 g/kg) or a placebo. Results showed that alcohol reduced driving precision, as evident by the increased within-lane deviation observed under the drug. Moreover, those individuals with poorer baseline skill levels showed the greater impairments in response to alcohol. The results highlight the importance of understanding interactions between driver skill level and the effects of alcohol and possibly other drugs.

Does co-morbid depression alter the inverse relationship between obesity and substance use disorders?

BACKGROUND: Substance use disorders and obesity are often inversely related to one another, hypothetically due to competition over shared neurobiological reward circuitry. However, obesity and substance use disorders share common risk factors, such as other psychiatric disorders. It is unknown whether the inverse relationship between obesity and substance use disorders continues to exist in the presence of shared risk factors. METHODS: For the current study, we examined the associations between major depression, alcohol and drug use disorders, and overweight/obesity status in a nationally representative sample of U.S. adults (n=40,715). RESULTS: Our findings demonstrated that adults with major depression were more likely to be obese, whereas adults with alcohol or drug use disorders were less likely to be obese. However, the inverse relationship between substance use and obesity continued to exist in adults with co-morbid depression. Adults with depression disorders co-morbid with alcohol (Relative Risk [RR]=0.63, 95% CI=0.47-0.84) or drug (RR=0.54, 95% CI=0.36-0.81) use disorders were less likely to be obese vs normal weight. CONCLUSIONS: Our findings provide support for the proposal that excess food consumption and excess drug use appear to compete over shared neurobiology even when the motivation to self-medicate with either food or substances might be elevated.