Serotonin transporter binding is reduced in seasonal affective disorder following light therapy.

OBJECTIVE: To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND ), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) during winter in seasonal affective disorder (SAD). 5-HTT BPND fluctuates seasonally to a greater extent in SAD relative to health. We hypothesized that in SAD, 5-HTT BPND would be reduced in the ACC and PFC following light therapy. METHODS: Eleven SAD participants underwent [11 C] DASB positron emission tomography (PET) scans to measure 5-HTT BPND before and after 2 weeks of daily morning light therapy. RESULTS: The primary finding was a main effect of treatment on 5-HTT BPND in the ACC and PFC (repeated-measures manova, F(2,9) = 6.82, P = 0.016). This effect was significant in the ACC (F(1,10) = 15.11 and P = 0.003, magnitude of decrease, 11.94%) and PFC (F(1,10) = 8.33, P = 0.016, magnitude of decrease, 9.13%). 5-HTT BPND also decreased in other regions assayed following light therapy (repeated-measures manova, F(4,7) = 8.54, P = 0.028) including the hippocampus, ventral striatum, dorsal putamen, thalamus and midbrain (F(1,10) = 8.02-36.94, P < 0.0001-0.018; magnitude -8.83% to -16.74%). CONCLUSIONS: These results demonstrate that light therapy reaches an important therapeutic target in the treatment of SAD and provide a basis for improvement of this treatment via application of [11 C]DASB PET.

Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (< 12 years), 2 adolescent (12-18 years), and 4 adults (>18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

Light therapy and serotonin transporter binding in the anterior cingulate and prefrontal cortex.

OBJECTIVE: To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND ), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) of healthy individuals during the fall and winter. Twenty-five per cent of healthy individuals experience seasonal mood changes that affect functioning. 5-HTT BPND has been found to be higher across multiple brain regions in the fall and winter relative to spring and summer, and elevated 5-HTT BPND may lead to extracellular serotonin loss and low mood. We hypothesized that, during the fall and winter, light therapy would reduce 5-HTT BPND in the ACC and PFC, which sample brain regions involved in mood regulation. METHOD: In a single-blind, placebo-controlled, counterbalanced, crossover design, [(11) C]DASB positron emission tomography was used measure 5-HTT BPND following light therapy and placebo conditions during fall and winter. RESULTS: In winter, light therapy significantly decreased 5-HTT BPND by 12% in the ACC relative to placebo (F1,9 = 18.04, P = 0.002). In the fall, no significant change in 5-HTT BPND was found in any region across conditions. CONCLUSION: These results identify, for the first time, a central biomarker associated with the intervention of light therapy in humans which may be applied to further develop this treatment for prevention of seasonal depression.

Gender differences in the association between stop-signal reaction times, body mass indices and/or spontaneous food intake in pre-school children: an early model of compromised inhibitory control and obesity.

BACKGROUND: Poor inhibitory control is associated with overeating and/or obesity in school-age children, adolescents and adults. The current study examined whether an objective and reliable marker of response inhibition, the stop-signal reaction time (SSRT), is associated with body mass index (BMI) z-scores and/or food intake during a snack test in pre-school children. METHODS: The current sample consisted of 193 pre-school children taking part in a longitudinal study of early brain development (Maternal Adversity, Vulnerability and Neurodevelopment (the MAVAN project)). Linear mixed-effect models were used to examine whether the SSRT measured at age 48 months associated with BMI z-scores and/or dietary intake during a laboratory-based snack test. RESULTS: After controlling for significant covariates including maternal BMI, there was a significant gender by SSRT interaction effect in predicting 48-month BMI z-scores. Post-hoc analysis revealed an association between longer SSRTs (poor response inhibition) and higher BMIs in girls but not boys. Across both girls and boys, longer SSRTs were associated with greater intake of carbohydrates and sugars during the snack test. The association between SSRT scores and BMI z-scores in girls was not statistically mediated by carbohydrate or sugar intake. CONCLUSIONS: At 48 months of age, slower response inhibition on the Stop-Signal Task associates with higher BMI z-scores in girls, and with higher intake of carbohydrates and sugars during a snack test across both genders. Ongoing follow-up of these children will help clarify the implications of these associations for longer term macronutrient intake, eating-related pathology and/or pathological weight gain over time.

Association between MC4R rs17782313 polymorphism and overeating behaviors.

BACKGROUND/OBJECTIVES: Melanocortins have a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behavior and depressed mood. SUBJECTS/METHODS: We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviors was obtained during the in-person assessment. RESULTS: BMI was associated with rs17782313 C allele; however, this finding did not survive correction for multiple testing (P = 0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviors, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n = 152). CONCLUSIONS: To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behavior, as well as to demonstrate possible mechanisms behind MC4R's influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating.

Better quality of mother-child interaction at 4 years of age decreases emotional overeating in IUGR girls.

BACKGROUND/OBJECTIVES: While most "fetal programming" area focused on metabolic disease, intrauterine growth restriction (IUGR) is also associated with a preference for less healthy food. Post-natal factors such as strained maternal-child interactions are equally related to obesogenic eating behaviors. We investigated if IUGR and the quality of the mother/child relationship affect emotional overeating in children. SUBJECTS/METHODS: Participants were 196 children from a prospective birth cohort (the MAVAN project). As part of the protocol at 4 years of age, mothers completed the Children Eating Behavior Questionnaire (CEBQ) and mother-child interactions were scored during a structured task. A GLM adjusted for BMI examined the interaction between the "Atmosphere" score (ATM) task, sex and IUGR on the emotional over-eating domain of the CEBQ. RESULTS: There was a significant interaction of BWR vs. sex vs. ATM (P = .02), with no effects of IUGR, sex or ATM. The model was significant for girls with low ATM scores (B = -2.035, P = .014), but not for girls with high (P = 0.94) or boys with high (P = .27) or low (P = .19) ATM scores. Only in IUGR girls, 48 months emotional over-eating correlated with BMI at that age (r = 0.560, P = 0.013) and predicted BMI in the subsequent years (r = 0.654, P = 0.006 at 60 months and r = 0.750, P = 0.005 at 72 months). CONCLUSIONS: IUGR and exposure to a negative emotional atmosphere during maternal-child interactions predicted emotional overeating in girls but not in boys. The quality of mother-infant interaction may be an important target for interventions to prevent emotional overeating and overweight in early development, particularly in girls with a history of IUGR.

The role of depression and childhood trauma on cortisol suppression in women with bulimia nervosa: a pilot study.

OBJECTIVE: Although some studies have shown cortisol nonsuppression following dexamethasone suppression test (DST) in current bulimia nervosa (BN), no study has looked at HPA axis abnormalities in behaviorally recovered BN patients. The purpose of this pilot study is to explore the role of current vs behaviorally recovered BN, as well as depression and childhood trauma in cortisol suppression in BN. METHODS: A 0.5 mg DST was performed on 21 patients with behaviorally recovered BN, 9 women with current BN and 14 controls. BN group also completed the Hamilton Depression Rating Scale and Childhood Trauma Questionnaire. RESULTS: There were no differences between the three groups in cortisol suppression, and BMI was not associated with cortisol levels following DST. Within the BN group, depression was significantly associated with afternoon cortisol nonsuppression (p=0.005). DISCUSSION: As researchers look for more accurate ways to identify biological phenotypes of BN, presence of comorbid depression may help explain differences in cortisol suppression.

Dopamine receptors D1 and D2 are related to observed maternal behavior.

The dopamine pathway and especially the dopamine receptors 1 and 2 (DRD1 and DRD2) are implicated in the regulation of mothering in rats. Evidence for this in humans is lacking. Here, we show that genetic variation in both DRD1 and DRD2 genes in a sample of 187 Caucasian mothers predicts variation in distinct maternal behaviors during a 30-min mother-infant interaction at 6 months postpartum. Two DRD1 single-nucleotide polymorphisms (SNPs rs265981 and rs686) significantly associated with maternal orienting away from the infant (P = 0.002 and P = 0.003, respectively), as did DRD1 haplotypes (P = 0.03). Two DRD2 SNPs (rs1799732 and rs6277) significantly associated with maternal infant-directed vocalizing (P = 0.001 and P = 0.04, respectively), as did DRD2 haplotypes (P = 0.01). We present evidence for heterosis in DRD1 where heterozygote mothers orient away from their infants significantly less than either homozygote group. Our findings provide important evidence that genetic variation in receptors critical for mothering in non-human species also affect human maternal behaviors. The findings also highlight the importance of exploring multiple dimensions of the complex human mothering phenotype.

Opiates, overeating and obesity: a psychogenetic analysis.

OBJECTIVE: This study provides an original perspective on the associations among endogenous opiates, overeating and obesity. The aim was to assess whether variability in the OPRM1 gene, as assessed by seven single-nucleotide polymorphisms, relates to individual differences in the preference for sweet and fatty foods. We also anticipated that these food preferences would be positively associated with binge eating, hedonic eating and emotionally driven eating-patterns of overeating that would, in turn, predict higher body mass index (BMI). DESIGN: Analysis of variance procedures examined genotype differences in food preferences; bivariate correlation coefficients examined the relationships among food preferences and the overeating variables; and a regression analysis tested the combined influences of the overeating variables on BMI. DNA was extracted from whole blood for the genotyping, and measures of food preferences and eating behaviours were obtained from well-validated self-report questionnaires. SUBJECTS: Participants were 300 healthy adult men and women recruited from the community. RESULTS: All the predicted associations were supported by statistically significant results. In particular, the G/G genotype group of the functional A118G marker of the OPRM1 gene reported higher preferences for sweet and fatty foods compared with the other two groups. Food preferences were also related to all overeating measures, which in turn accounted for a substantial proportion of the variance in BMI. CONCLUSIONS: Our findings suggest that some of the diversity in the preference for highly palatable foods can be explained by genotypic differences in the regulation of mu opioid receptors. The associations reported in this paper are important from a public-health perspective because of the abuse potential of sweet-fat foods and their strong relationship with obesity.

Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.

Maternal behavior in the new mother is a multidimensional set of responses to infant cues that are influenced by the mother's early life experiences. In this study, we wanted to test if mothers' early life experiences and mothers' genotype have interactive effects on maternal behaviors and attitudes, something which has not been previously explored. In a sample of 204 mothers, we assessed maternal genotype at the serotonin transporter-linked polymorphic region (5-HTTLPR) and an adjacent upstream polymorphism (rs25531), together giving rise to three alleles: short (S), L(G) and L(A). Controlling for maternal age and parity, we showed that this genotype can predict differences in maternal sensitivity at 6 months postpartum: mothers with an S (or the functionally similar L(G)) allele were more sensitive than mothers who lacked the allele during a 30-min recorded mother-infant interaction (F (4,140) = 3.43; P = 0.01). Furthermore, we found highly significant gene-environment interactions in association with maternal behavior, such that mothers with no S or L(G) alleles oriented away more frequently from their babies if they also reported more negative early care quality (F (5,138) = 3.28; P = 0.008). Finally, we found significant gene-environment associations with maternal attitudes; mothers with the S allele and with greater early care quality scored higher on ratings of their perceived attachment to their baby (F (5,125) = 3.27; P = 0.008). The regression results show significant interactions between the reported quality of care mothers received from their own parents and genotype on both their frequency of orienting away from the infant during the interaction (F(5, 138) = 3.28; P = 0.008, Fig. 1a) and their perceived attachment feelings to the infant (F(5, 125) = 3.27; P = 0.008, Fig. 1b); however the direction of the effects for these two outcome measures were different from one another. With increasing care quality, mothers with the L(A)L(A) genotype (no S or L(G) allele) oriented away less frequently, while S or L(G) allele carriers showed no significant change. In contrast, with increasing early care quality. L(A)L(A) (no S or L(G) allele) mothers scored lower on perceived attachment to their infants, whereas S or L(G) allele carrying mothers scored higher. [corrected].

Investigating associations between cortisol and cognitive reactivity to sad mood provocation and the prediction of relapse in remitted major depression.

OVERVIEW: In remitted depressed patients, an increase in dysfunctional thoughts following a sad mood induction can predict relapse over 18 months. The current analysis examined whether salivary cortisol levels could also predict relapse in these same individuals. METHOD: 99 subjects with major depression were first treated to full remission using either antidepressant medication or cognitive behavioural therapy. While in the remitted state, subjects were exposed to sad music to trigger dysfunctional thoughts. In a subset of 55 subjects, salivary cortisol levels taken before and after the mood challenge were also obtained. RESULTS: Unexpectedly, cortisol levels tended to decrease rather than increase following the mood challenge, suggesting that anticipation of the mood challenge was more stressful than the challenge itself. We thus used pre-challenge cortisol levels as the main grouping variable. Based on Kaplan-Meier survival curves, among subjects with low pre-challenge cortisol levels, those with a history of three or more prior episodes had significantly higher rates of relapse than did subjects with two or less prior episodes. In subjects with high pre-challenge cortisol levels, there was no significant difference in rates of relapse based on the number of prior episodes. CONCLUSION: In depressed patients with few prior episodes, assessing risk of relapse and thus establishing the duration for treatment can be a difficult clinical problem. Pending replication, the current results suggest that high anticipatory cortisol levels may have utility in predicting relapse even in patients with few prior episodes.

The serotonin-1Dbeta receptor gene and severity of obsessive-compulsive disorder in women with bulimia nervosa.

BACKGROUND: There is significant evidence that eating disorders have an important biological overlap with obsessive-compulsive disorder (OCD), though the specific mediators of this relationship remain unclear. Recent evidence suggests that the G861C polymorphism of the 5HT-1Dbeta receptor gene and the G allele in particular may play a role in OCD. We thus hypothesized that, among a heterogenous group of probands with bulimia nervosa (BN), this same G allele might predict the presence and/or severity of OCD pathology. METHODS: 165 consecutive female probands with BN were genotyped for the G861C polymorphism of the 5HT-1Dbeta receptor gene. Rates of full syndrome OCD, partial syndrome OCD and no OCD were compared across the three genotypic groups defined by this polymorphism. RESULTS: 45 out of 165 BN probands (27.3%) had either full or partial syndrome OCD. In the full sample, there was a significant difference in the distribution of the three diagnostic groups by genotype (chi2=10.07, df=4, p=.039). The G861C polymorphism did not strongly predict which probands had any vs. no OCD pathology. However, among the 45 probands with OCD symptoms, the G861C polymorphism did strongly differentiate full syndrome vs. partial syndrome OCD (chi2=9.26, df=2, p=.01; odds ratio for full syndrome OCD with GG genotype=7.69, 95% CI=1.45-40.9). DISCUSSION: In women with BN, the G861C polymorphism of the 5HT-1Dbeta gene does not appear to be associated with the generation of OCD symptoms; however, it might directly or indirectly be associated with a modulatory effect on syndrome severity in probands otherwise predisposed to OCD. While preliminary and in need of replication in other samples, this is the first association study to suggest how a particular gene might influence OCD pathology in an eating disorder population.

Initial anatomic investigations of the I-gel airway: a novel supraglottic airway without inflatable cuff.

The I-gel airway is a novel supraglottic airway that uses an anatomically designed mask made of a gel-like thermoplastic elastomer. We studied the positioning and mechanics of this new device in 65 non-embalmed cadavers with 73 endoscopies (eight had repeat insertion), 16 neck dissections, and six neck radiographs. A full view of the glottis (percentage of glottic opening score 100%) occurred in 44/73 insertions, whereas only 3/73 insertions had epiglottis-only views. Including the eight repeat insertions with a different size, a glottic opening score of > 50% was obtained in all 65 cadavers. The mean percentage of glottic opening score for the 73 insertions was 82% (95% confidence interval 75-89%). In each of the neck dissections and radiographs the bowl of the device covered the laryngeal inlet. We found that the I-gel effectively conformed to the perilaryngeal anatomy despite the lack of an inflatable cuff and it consistently achieved proper positioning for supraglottic ventilation.

Symptoms of attention deficit hyperactivity disorder in severely obese women.

OBJECTIVE: Past and current symptoms of Attention Deficit Hyperactivity Disorder (ADHD) were assessed in a clinical sample of severely obese females. METHOD: Core symptoms of ADHD were examined in 75 consecutive, severely obese (BMI > or = 35) women referred to a medical specialist for the non-surgical treatment of obesity. Subjects completed both a retrospective report of childhood symptoms of ADHD (Wender Utah Scale) and two standardized adult ADHD symptom scales. RESULTS: The frequency of clinically suggestive elevations in ADHD scores was substantially and significantly higher than the normative samples in 9 out of 11 symptom subscales. Inattentive symptoms, but not hyperactive symptoms of ADHD, were frequently reported. Overall, 26.7% of the sample reported significant symptoms of ADHD in both childhood and adulthood. CONCLUSIONS: This preliminary study suggests that severely obese women report significant symptomatology related to both childhood and adult ADHD.

Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder.

There is significant evidence that altered dopamine activity plays a role in seasonal affective disorder (SAD). The current study examined three separate genetic hypotheses for SAD related to the 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), a variant associated with decreased affinity for dopamine. We examined the possible contribution of 7R to the overall expression of SAD, attention deficit disorder (ADD) comorbidity, and body weight regulation. As part of an ongoing genetic study of increased eating behavior and mood in female subjects, 108 women with winter SAD and carbohydrate craving/weight gain were administered the Wender-Utah Rating Scale to measure childhood ADD symptomatology, and a questionnaire to assess maximal lifetime body mass index (BMI). To test for an association between 7R and the categorical diagnosis of SAD, the transmission disequilibrium test (TDT) was used in a subsample of probands providing familial DNA. Standard parametric tests were used to compare childhood ADD symptoms and maximal lifetime BMI across the two genotypic groups defined by the presence or absence of 7R. The TDT found no initial evidence for an association between 7R and the categorical diagnosis of SAD. However, 7R carriers reported significantly greater inattention and dysphoria in childhood (p=0.01 and 0.001, respectively) and a higher maximal lifetime BMI (p=0.007) than did probands without this allele. Furthermore, excluding probands with extreme obesity (maximal BMI >40), a strong correlation was found linking childhood inattentive symptoms and maximal lifetime BMI (r=0.35, p=0.001). In overeating women with SAD, the 7R allele of DRD4 may be associated with a unique developmental trajectory characterized by attentional deficits and dysphoria in childhood and mild to moderate obesity in adulthood. This developmental course may reflect different manifestations of the same underlying vulnerability related to central dopamine dysfunction. Given the possibility of population stratification when studying genotype/phenotype relationships, future use of genomic controls and replication of our findings in other overeating and/or ADD populations are needed to confirm these initial results.

The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.

BACKGROUND: Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case-control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. METHOD: One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. RESULTS: No association between 5-HTTLPR and SAD was found in the new case-control material, in the combined analysis of all samples, or when only including 316 patients with controls (N = 298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2.24 (1.03-4.91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. CONCLUSIONS: These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder.

INTRODUCTION: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the 5-HT2A receptor gene (HTR2A) contributes to both SAD and ADHD. The current study investigated whether variation in HTR2A was associated with symptoms of childhood ADHD in adult women with SAD. METHOD: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA. RESULTS: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD. LIMITATIONS: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall. CONCLUSION: These preliminary results suggest a possible association between variation in HTR2A, childhood ADHD, and the later development of SAD in women.

Polymorphism of the serotonin 5-HT1B receptor gene (HTR1B) associated with minimum lifetime body mass index in women with bulimia nervosa.

BACKGROUND: Preclinical research has shown that the serotonin-1B receptor has important modulatory effects on feeding behavior and thus body weight. In the current study, we examined whether genetic variation of the serotonin-1B receptor was associated with minimum and maximum lifetime body mass indices (BMIs) in a sample of women with bulimia nervosa (BN). METHODS: Ninety-eight women with BN were genotyped based on the G861C polymorphism of the serotonin-1B receptor gene (HTR1B). Minimum and maximum lifetime BMIs were compared across the three genotypic groups using analysis of variance. RESULTS: There was a highly significant difference in minimum lifetime BMI across the three genotypic groups (p =.001). Both the G/C and C/C genotypes were associated with significantly lower minimum lifetime BMIs than was the G/G genotype. Maximum lifetime BMI was not significantly different across groups. These results were not attributable to different lifetime rates of anorexia nervosa across the three genotypic groups. CONCLUSIONS: These preliminary findings suggest a possible association between HTR1B genetic polymorphism and minimum lifetime BMI in women with BN. These findings may shed light on why, in response to dieting, some BN patients achieve lower BMIs, whereas others have a natural limitation to their weight loss. Pending replication in a larger sample, these findings point to a possible genetic factor of fundamental importance to the BN population.