Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients.

INTRODUCTION: Alcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. METHODS: This retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. RESULTS: There were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). CONCLUSION: Protocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

Reward and inhibition in obesity and cigarette smoking: Neurobiological overlaps and clinical implications.

Cigarette smoking and obesity are the leading causes of premature morbidity and mortality and increase the risk of all-cause mortality four-fold when comorbid. Individuals with these conditions demonstrate neurobiological and behavioral differences regarding how they respond to rewarding stimuli or engage in inhibitory control. This narrative review examines the role of reward and inhibition in cigarette smoking and obesity independently, as well as recent research demonstrating an effect of increased body mass index (BMI) on neurocognitive function in individuals who smoke. It is possible that chronic smoking and overeating of highly palatable food, contributing to obesity, dysregulates reward neurocircuitry, subsequently leading to hypofunction of brain networks associated with inhibitory control. These brain changes do not appear to be specific to food or nicotine and, as a result, can potentiate continued cross-use. Changes to reward and inhibitory function due to increased BMI may also make cessation more difficult for those comorbid for obesity and smoking.

Exploration of the influence of body mass index on intra-network resting-state connectivity in chronic cigarette smokers.

BACKGROUND: Obesity and cigarette smoking are two leading preventable causes of death. Previous research suggests that comorbid smoking and obesity likely share neurobehavioral underpinnings; however, the influence of body mass index (BMI) on resting-state functional connectivity (rsFC) in smokers remains unknown. In this study, we explore how BMI affects rsFC and associations between rsFC and smoking-related behavior. METHODS: Treatment-seeking cigarette smokers (N = 87; 54 % men) completed a BOLD resting-state fMRI scan session. We grouped smokers into BMI groups (N = 23 with obesity, N = 33 with overweight, N = 31 lean) and used independent components analysis (ICA) to identify the resting state networks commonly associated with cigarette smoking: salience network (SN), right and left executive control networks (ECN) and default mode network (DMN). Average rsFC values were extracted (p < 0.001, k = 100) to determine group differences in rsFC and relationship to self-reported smoking and dependence. RESULTS: Analyses revealed a significant relationship between BMI and connectivity in the SN and a significant quadratic effect of BMI on DMN connectivity. Heavier smoking was related to greater rsFC in the SN among lean and obese groups but reduced rsFC in the overweight group. CONCLUSIONS: Findings build on research suggesting an influence of BMI on the neurobiology of smokers. In particular, dysfunction of SN-DMN-ECN circuitry in smokers with overweight may lead to a failure to modulate attention and behavior and subsequent difficulty quitting smoking. Future research is needed to elucidate the mechanism underlying the interaction of BMI and smoking and its impact on treatment.

Influence of the natural hormonal milieu on brain and behavior in women who smoke cigarettes: Rationale and methodology.

Women experience more severe health consequences from smoking, have greater difficulty quitting, and respond less favorably to nicotine replacement therapy than men. The influence of fluctuating ovarian hormones, specifically estradiol (E) and progesterone (P), on brain and behavioral responses during exposure to smoking reminders (i.e., cues) may be a contributing factor. Results from our laboratory suggest that women in the late follicular phase of their menstrual cycle (MC) have enhanced smoking cue (SC) vulnerabilities and reduced functional connectivity in neurocircuitry underlying cognitive control, potentially placing them at greater risk for continued smoking and relapse. The primary aim of this study is to examine and link hormonal status with brain and behavioral responses to SCs over the course of three monthly MCs in naturally cycling women who are chronic cigarette smokers. This longitudinal, counterbalanced study collects brain and behavioral responses to SCs at three time points during a woman's MC. Participants complete psychological and physical examinations, biochemical hormonal verification visits, and at least three laboratory/neuroimaging scan visits. The scan visits include a 10-min SC task during blood oxygen level-dependent (BOLD) data acquisition and are timed to occur during the early follicular phase (low E and P), late follicular phase (high E, unopposed by P), and mid-luteal phase (high P, high E). The primary outcomes include brain responses to SCs (compared to non-SCs), subjective craving, E and P hormone levels, and behavioral responses to SCs. This study addresses a critical gap in our knowledge: namely, the impact of the natural hormonal milieu on brain and behavioral responses to SCs, a powerful relapse trigger. Additionally, this study will provide a roadmap for human sex differences researchers who are obliged to consider the often confounding cyclic hormonal fluctuations of women.

Smoking-induced craving relief relates to increased DLPFC-striatal coupling in nicotine-dependent women.

BACKGROUND: Craving is a major contributor to drug-seeking and relapse. Although the ventral striatum (VS) is a primary neural correlate of craving, strategies aimed at manipulating VS function have not resulted in efficacious treatments. This incongruity may be because the VS does not influence craving in isolation. Instead, craving is likely mediated by communication between the VS and other neural substrates. Thus, we examined how striatal functional connectivity (FC) with key nodes of networks involved in addiction affects relief of craving, which is an important step in identifying viable treatment targets. METHODS: Twenty-four nicotine-dependent non-abstinent women completed two resting-state (rs) fMRI scans, one before and one following smoking a cigarette in the scanner, and provided craving ratings before and after smoking the cigarette. A seed-based approach was used to examine rsFC between the VS, putamen and germane craving-related brain regions; the dorsolateral prefrontal cortex (dlPFC), the posterior cingulate cortex, and the anterior ventral insula. RESULTS: Smoking a cigarette was associated with a decrease in craving. Relief of craving correlated with increases in right dlPFC- bilateral VS (r = 0.57, p = 0.003, corrected) as did increased right dlPFC-left putamen coupling (r = 0.62, p = 0.001, corrected). CONCLUSIONS: Smoking-induced relief of craving is associated with enhanced rsFC between the dlPFC, a region that plays a pivotal role in decision making, and the striatum, the neural structure underlying motivated behavior. These findings are highly consistent with a burgeoning literature implicating dlPFC-striatal interactions as a neurobiological substrate of craving.

An exploration of associations between smoking motives and behavior as a function of body mass index.

Objective: Cigarette smoking and obesity are the leading causes of premature morbidity and mortality and increase the risk of all-cause mortality four-fold when comorbid. Although research suggests that smoking motives may differ based on body mass index (BMI), it is unclear how these differences translate to smoking behavior. Method: Three groups of adults who smoke cigarettes (N = 79; obese n = 25, overweight n = 30, and lean n = 24) completed measures of smoking and the Smoking Motivations Questionnaire. Groups did not differ on age, education, cigarettes per day (CPD), pack-years, or nicotine dependence, as measured by the Fagerström Test for Cigarette Dependence (FTCD). Results: Analyses revealed different associations between reasons for smoking and smoking behavior depending on lean, overweight, or obesity status. Participants (N = 37 female, average age 39.8 years) self-reported smoking was positively associated with Addictive, and Automatic subscale scores among lean participants, with only the Addictive subscale score among those with overweight, and only the Automatic subscale score among those with obesity. Post hoc MANCOVA analysis revealed a significant interaction effect of Group x Automatic Smoking on Pack-years (F(2, 79)=3.34, p = 0.04). Conclusion: Findings suggest smoking motives are differentially associated with smoking behavior in adults who smoke depending on weight status. The daily smoking rate of participants with obesity may be less related to the addictive quality of smoking, and automaticity may be less associated with smoking history in those with overweight. Additional research on the influence of BMI on cigarette smoking is necessary to fully elucidate how obesity may impact treatment outcomes to optimize smoking cessation treatment among those with excess body weight.

Relationship Between Psychological Distress and Cognitive Function Differs as a Function of Obesity Status in Inpatient Heart Failure.

Heart failure (HF) is a chronic medical condition rapidly growing in prevalence. Evidence links HF to cognitive decline, obesity, and psychological distress. The current study examined the association between cognitive function and ejection fraction (EF%), anxiety, depression, and obesity in inpatient HF. Patients completed the Generalized Anxiety Disorder 7-Item Scale (GAD-7), Patient Health Questionnaire 9-Item Scale (PHQ-9), and Mini-Cog while hospitalized for HF. Additional demographic and medical information was gathered via chart review. All models controlled for age. Of 117 patients assessed (49% male), 55% (n = 64) were obese. ANCOVA analyses were conducted comparing those with obesity and without on cognitive function: model A included EF%, model B included depression, and model C included anxiety. All three models were significantly related to cognitive function. There was a significant interaction effect of EF% and obesity and of anxiety and obesity to predict Mini-Cog scores. Post hoc partial correlational analyses revealed that anxiety was negatively associated with Mini-Cog scores among only patients without obesity. Depression was not significantly related to cognitive function in either group. However, patients with obesity demonstrated higher depression and anxiety than patients without. Results suggest that at lower EF%, and with higher anxiety, patients without obesity may be at greater risk of cognitive dysfunction than those with obesity. Cognitive dysfunction among HF patients with obesity may be independent of psychological distress. These findings may reflect the "obesity paradox" observed among HF patients, in that patients with obesity may have a different biopsychosocial presentation, which may lead to unexpected clinical outcomes. Further research is necessary to articulate the relationship of obesity and cognitive function in HF.

Neural Insensitivity to the Effects of Hunger in Women Remitted From Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa. METHODS: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity. RESULTS: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group. CONCLUSIONS: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

Double jeopardy: Comorbid obesity and cigarette smoking are linked to neurobiological alterations in inhibitory control during smoking cue exposure.

Obesity and cigarette smoking are two of the leading preventable causes of death in the United States. Research suggests that overlapping pathophysiology may contribute to obesity and nicotine use disorder (NUD), yet no studies have investigated the effect of obesity on neural response to reward stimuli in NUD. This study used arterial spin-labeled perfusion functional magnetic resonance imaging (fMRI) to examine neural responses during exposure to smoking versus nonsmoking cues in 79 treatment-seeking participants with NUD, 26 with normal weight, 28 with overweight, and 25 with obesity. Given that deficits in behavioral inhibitory control have been associated with both obesity and NUD, participants completed an affect-congruent Go/NoGo task to assess the effect of body mass index (BMI) on this construct in NUD. Analyses revealed that BMI was negatively associated with activation in the right dorsolateral prefrontal cortex (dlPFC) in response to smoking cues, with significantly reduced response in smokers with overweight and smokers with obesity compared with normal-weight smokers. In addition, greater commission errors on the Go/NoGo task were correlated with reduced neural response to smoking cues in the right dlPFC only among those with obesity. Together, these findings provide evidence that obesity in treatment-seeking NUDs is related to neurobiological alterations in inhibitory control over cue-potentiated behaviors, suggesting that smoking cessation may be more difficult in individuals with comorbid NUD and obesity than in those without, requiring treatment strategies tailored to meet their unique needs.

A process approach to verbal memory assessment: Exploratory evidence of inefficient learning in women remitted from anorexia nervosa.

Introduction: Anorexia nervosa (AN) is associated with deficits in set-shifting and cognitive flexibility, yet less is known about the persistence of these deficits after recovery and how they might contribute to reported difficulties organizing and learning new information. To address this question, the current study applied a process-focused approach, that accounts for errors and strategies by which a score is achieved, to investigate the relationship between verbal memory and executive function in women remitted from AN. Method: Twenty-six women remitted from anorexia nervosa (RAN) and 25 control women (CW) aged 19-45 completed the California Verbal Learning Test, Second edition (CVLT-II) and the Wisconsin Card Sorting Test (WCST). Groups were compared on overall achievement scores, and on repetition, intrusion, and perseverative errors on both tests. Associations between learning and memory performance and WCST errors were also examined. Results: RAN and CW groups did not differ on overall CVLT-II learning and memory performance or errors on the WCST, though the RAN group trended towards greater WCST non-perseverative and total errors. On the CVLT-II, the RAN group made significantly more repetition errors than CW (p = 0.010), and within-trial perseveration (WTP) errors (p = 0.044). For the CW group, CVLT-II learning and memory performance were negatively associated with errors on the WCST, whereas among RAN, primarily delayed memory was negatively correlated with WCST errors. Notably, for RAN, greater WCST perseverative responses were correlated with greater CVLT-II repetition and WTP errors, showing the convergence of perseverative responding across tasks. Conclusions: Despite similar overall learning and memory performance, difficulties with executive control seem to persist even after symptom remission in patients with AN. Results indicate an inefficient learning process in the cognitive phenotype of AN and support the use of process approaches to refine neuropsychological assessment of AN by accounting for strategy use.

Response in taste circuitry is not modulated by hunger and satiety in women remitted from bulimia nervosa.

Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed. Twenty-six women remitted from BN (RBN) and 22 control women (CW) were administered water and sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a standardized breakfast. Significant Group × Condition interactions were found in the left putamen, insula, and amygdala. Post hoc analyses revealed CW were significantly more responsive to taste stimuli when hungry versus fed in the left putamen and amygdala. In contrast, RBN response did not differ between conditions. Further, RBN had greater activation in the left amygdala compared with CW when fed. Findings suggest that RBN neural response to rewarding stimuli may not be modulated by metabolic state. Data raise the possibility that disinhibited eating in BN could result from a failure to devalue food reward when fed, resulting in an exaggerated response. (PsycINFO Database Record

Anxiety Impacts Cognitive Inhibition in Remitted Anorexia Nervosa.

OBJECTIVE: Eating disorders are complex psychiatric disorders, associated with alterations in neural and cognitive functioning. Research suggests inhibition and set-shifting deficits in anorexia nervosa (AN), but less is known about the persistence of these deficits after recovery, or their relationship to comorbid psychiatric symptoms. METHOD: Women aged 19-45 remitted from AN (RAN, N = 47) and controls (CW, N = 24) completed the Delis-Kaplan Executive Function System Color-Word Interference Test. It was hypothesized that RAN, and those with higher anxiety or depression, would demonstrate worse Inhibition and Switching task performance than CW. RESULTS: Differences in performance between groups trended toward significance on Inhibition Ratio (p = 0.08) but were nonsignificant on Inhibition/Switching Ratio (p = 0.93). A model including State Anxiety and diagnosis revealed a significant independent effect of State Anxiety (p = 0.026), but not of diagnosis nor their interaction. Regressing State Anxiety on Color-Word Interference Test Inhibition among just the RAN group was significant [ß = 0.37, t(46) = 2.63, p = 0.012] but among just CW was not (p = 0.54). DISCUSSION: Interference control for neutral stimuli is influenced by anxiety in women with a history of AN. Anxiety is linked with greater symptom severity among AN individuals, and state anxiety may account for larger deficits seen on tasks using disorder-specific stimuli. Future research is warranted to elucidate the nature of neuropsychological deficits in eating disorders. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.

Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food.

Delayed discounting and hedonic hunger in the prediction of lab-based eating behavior.

Research suggests that characteristics identified in obese individuals, such as impulsive decision-making and hedonic hunger, may exist in nonobese populations. This study examined the independent and interactive effects of impulsive decision-making (measured via delay discounting, DD) and hedonic hunger (assessed with the Power of Food Scale, PFS) on food intake. Female participants (N=78) ate a self-determined amount of plain oatmeal, completed self-report measures and the delay discounting task, and participated in a sham taste test of palatable sweet and salty foods. Unexpectedly, PFS and DD scores interacted to predict consumption of the total amount of food consumed, and of oatmeal alone, but not of snack food alone. High-PFS participants consumed more when also high in DD, while low-PFS participants showed the opposite pattern of consumption. The findings identify variables that may increase propensity toward overconsumption and potential weight gain; future research is necessary to evaluate the utility of these constructs to predict increases in BMI over time.

The Binge and the Brain.

Who hasn't dipped into that pint of Häagen-Dazs with the best of intentions and ended up finishing the entire container? Knowing where the line is when it comes to out-of-control impulse consumption is at the heart of binge-eating disorder (BED), a newly recognized mental condition that effects affects millions of people and that we are just beginning to better understand-from both a neurobiological and clinical standpoint.

Hunger does not motivate reward in women remitted from anorexia nervosa.

BACKGROUND: Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN. METHODS: Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN. RESULTS: Interactions of Group (RAN, CW) × Visit (hunger, satiety) revealed that, for the CW group, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in the RAN group. A main effect of group revealed elevated response in the middle frontal gyrus for the RAN group compared with the CW group. CONCLUSIONS: Women remitted from AN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to the motivational drive of hunger may explain the ability of individuals with AN to restrict food when emaciated. Difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this disorder.

Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

The primary defining characteristic of a diagnosis of an eating disorder (ED) is the "disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food" (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

Differential reward response to palatable food cues in past and current dieters: a fMRI study.

OBJECTIVE: Prior neuroimaging research has shown that restrained and unrestrained eaters demonstrate differential brain activation in response to food cues that parallels their food intake in lab studies. These findings were extended by comparing brain activation in response to food cues in normal weight nondieters, historical dieters, and current dieters under the conditions that mimicked past lab studies. METHODS: Participants (N = 30) were shown pictures of highly and moderately palatable food and neutral cues while being scanned in an fMRI BOLD paradigm following an 8-h fast and again after a liquid meal. RESULTS: In the Fed state, historical dieters showed elevated reward circuitry activation in response to highly palatable food, as compared to nondieters and current dieters. In contrast, current dieters did not show the same pattern of activation as historical dieters, despite their shared history of frequent weight-loss dieting. CONCLUSIONS: The parallels between eating behavior and regional brain activation across groups suggest that (1) a neurophysiological response which could represent a vulnerability to overeat exists in some normal weight young women that may increase susceptibility to weight gain in the long term, and (2) current dieting temporarily reverses this vulnerability.

The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial.

STUDY OBJECTIVES: In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on γ-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia. DESIGN: In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning. SETTING: Academic research center. PARTICIPANTS: Twenty-one chronic, medicated schizophrenia outpatients. MEASUREMENTS AND RESULTS: We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement. CONCLUSION: Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia.

The generation and inhibition of hedonically-driven food intake: behavioral and neurophysiological determinants in healthy weight individuals.

Given the progressive weight gain of populations in numerous countries, it can be presumed that many people eat beyond the point of nutritional repletion, in other words, for hedonic rather than homeostatic reasons. This kind of overeating is hypothesized to be due to a combination of obesogenic food environments, hyperresponsivity to food reward and deficits in inhibiting pleasure-based food intake. This paper explores the interrelationship of the latter two constructs and their neurobiological underpinnings. It also examines the potential brain changes that may take place during the course of repeated hedonic overeating and weight gain. It is hypothesized that fronto-striatal circuitry plays a primary role in this process, and that, over time, inhibitory control is eroded as reward responsiveness to highly palatable food cues increases. The unique neurobiological profile of normal weight but at-risk individuals may perpetuate continued weight gain; the neurobehavioral consequences of overeating and weight may make the permanent reversal of such weight gain infeasible.