Binge Eating

Introduction

Binge eating is characterized by consuming an unusually large amount of food within a discrete period, typically less than two hours, accompanied by a subjective sense of loss of control over the eating behavior.^[1]This behavior is a trans-diagnostic feature of various eating disorders, serving as a defining symptom of bulimia nervosa and binge eating disorder, and potentially occurring in anorexia nervosa.^[1] It is a significant public health concern, estimated to affect 4.5% of the United States general population.^[2]

Clinical Relevance

The clinical significance of binge eating is further highlighted by its frequent co-occurrence with other psychiatric conditions. Bipolar disorder (BD), for instance, is positively associated with eating dysregulation traits, including binge eating behavior.^[1]Studies indicate that binge eating occurs in over 25% of individuals with BD, a rate considerably higher than in the general population.^[2]This comorbidity is associated with a greater psychiatric and general medical burden, suggesting that BD with comorbid binge eating may represent a distinct and important clinical subtype.^[1] Understanding the genetic architecture of such specific sub-phenotypes is crucial for uncovering the complex inheritance patterns of conditions like BD.^[1]

Biological Basis

Both binge eating and bipolar disorder are highly heritable conditions. The heritability of BD is estimated between 60% and 85%, while that of binge eating, including broadly defined binge eating, ranges from 46% to 74%.^[3]Furthermore, parental BD has been identified as a risk factor for eating disorders, including those involving binge eating, in offspring.^[4]Genetic studies have begun to explore the shared and unique genetic factors underlying these conditions. Genome-wide association studies (GWAS) have implicated specific genetic variants in the etiology of binge eating, particularly in the context of BD comorbidity. For example, a genome-wide significant association was found between single nucleotide polymorphisms (SNPs) in thePRR5-ARHGAP8gene region and binge eating in BD cases, with a notable variant beingrs726170 .^[1] PRR5-ARHGAP8 is a fusion protein involving PRR5, a subunit of mTORC2 (a kinase involved in food intake regulation), and ARHGAP8, a protein mediating Rho GTPase signaling pathways.^[1] Another GWAS identified a genome-wide significant association with SNP rs111940429 in an intergenic region near PPP1R2P5when comparing BD cases with comorbid binge eating to non-BD controls.^[1] Additionally, the APOBgene has been implicated in bipolar disorder with comorbid binge eating history.^[1]While some candidate gene studies suggested associations between binge eating and genes likeFTO in adolescents, HTR2A in young women, and NT5C1B in female twins, these findings were not consistently replicated in broader GWAS.^[5] Further research into these genetic associations, including the regulatory functions of implicated SNPs like rs726170 and rs8139558 which are linked to transcription factor binding sites and enhancer regions.^[1]is critical for understanding the biological mechanisms underlying binge eating and its clinical manifestations.

Methodological and Sample Size Constraints

The investigations into the genetics of binge eating are subject to several methodological constraints, primarily stemming from limited sample sizes. For instance, one discovery sample included only 206 bipolar disorder cases with binge eating, a number that, despite efforts to reduce phenotypic heterogeneity for increased power, inherently restricts the ability to detect genetic variants with moderate effects.^[6]Such limitations necessitate much larger cohorts to comprehensively identify additional genetic risk factors contributing to binge eating.^[1] The challenge of replicating genetic findings, a known issue for complex disorders like bipolar disorder, is often exacerbated by these moderate effect sizes, making it difficult to establish robust genetic associations without substantial sample power.^[1]

Phenotypic Definition and Diagnostic Specificity

A significant limitation in understanding binge eating genetics arises from the variability in its definition across different studies and datasets. For example, binge eating was defined as a lifetime history of food binges in one cohort, while another used a more recent criterion of eating a large amount of food with a sense of loss of control within the last six months.^[1]This inconsistency can introduce heterogeneity into the phenotype, complicating the interpretation and comparability of findings. Furthermore, the absence of binge eating history information in control subjects across several analyses means researchers cannot definitively determine whether observed genetic associations reflect a general risk for binge eating or a specific risk factor for binge eating as a comorbidity of bipolar disorder.^[1]This lack of control data hinders the ability to distinguish whether identified single nucleotide polymorphisms are associated with bipolar disorder, binge eating, or an interaction between the two conditions.^[6]

Generalizability and Remaining Knowledge Gaps

The generalizability of findings is constrained by the demographic characteristics of the study populations. To mitigate potential population stratification, some analyses were exclusively performed on European American subjects, which limits the applicability of the results to individuals of other ancestries.^[6]Moreover, the studies faced challenges in replicating previously suggested candidate gene associations for binge eating or related eating disorders, such as variants inFTO and HTR2A in adolescents and young women, respectively, and NT5C1Bin female twins with bulimia nervosa spectrum.^[1]This highlights the complex genetic architecture of these traits and the need for broader replication efforts. While genetic associations are identified, the precise causal pathways and functional mechanisms through which these variants influence binge eating behavior, particularly in the context of bipolar disorder, remain largely unknown, underscoring the necessity for future longitudinal and functional research.^[6]

Variants

Several genetic variants, particularly single nucleotide polymorphisms (SNPs), have been implicated in binge eating behavior, often in the context of co-occurring conditions like bipolar disorder. These variants span regions encoding functional proteins, long non-coding RNAs, and intergenic stretches, suggesting a complex genetic architecture underlying appetite regulation and impulse control. Understanding their roles offers insight into the biological pathways contributing to binge eating.

A significant focus in the genetics of binge eating has been on the_PRR5-ARHGAP8_ read-through transcript, a fusion protein combining elements from _PRR5_ and _ARHGAP8_. _PRR5_is a component of mTORC2, a crucial serine/threonine kinase involved in regulating food intake, while_ARHGAP8_ belongs to the RhoGAP family, mediating signaling pathways essential for cellular processes. The variant rs726170 within this region has shown a genome-wide significant association with binge eating in individuals with bipolar disorder, suggesting its involvement in this complex comorbidity.^[1] This SNP is in high linkage disequilibrium with other variants located at binding sites for the transcription factor STAT3, and also with rs8139558 , an enhancer region marked by H3K4me1 histone marks in adipose tissues, indicating a potential regulatory role in gene expression relevant to metabolic and neural functions.^[1] Another variant, rs6006893 , also located within or near the _PRR5-ARHGAP8_locus, further underscores the importance of this region in influencing the neurobiological underpinnings of binge eating and related psychiatric traits.

Other variants linked to binge eating are found in non-coding or intergenic regions, hinting at complex regulatory mechanisms. The variantrs111940429 , located in an intergenic region associated with _LINC01789_ and _LINC01885_, showed a genome-wide significant association when comparing individuals with bipolar disorder and binge eating to controls.^[1] Similarly, rs17810023 , associated with _RPL17P25_ and _RPSAP72_, is situated near RP11–250B2.3, an identified long non-coding RNA (lncRNA).^[1] LncRNAs and pseudogenes like _RPL7P40_ and _PSMC1P8_, associated with rs73057489 , play critical roles in regulating gene expression, influencing neural development, synaptic plasticity, and metabolic pathways that are central to appetite control and reward processing . Variants in these regions, including rs182107583 near _MMADHC-DT_, can subtly alter the regulatory landscape, affecting the expression of nearby genes involved in neurodevelopment or metabolism, thereby contributing to susceptibility to binge eating behaviors.^[7]Further genetic associations highlight the interplay between metabolic and neurological systems in binge eating. The_APOB_gene, encoding apolipoprotein B, a key component of low-density lipoprotein (LDL), has been implicated in bipolar disorder with comorbid binge eating history.^[6] Variants such as rs10198175 in the region encompassing _LINC02850_ and _APOB_ may influence lipid metabolism and brain function, impacting pathways related to satiety and reward. The variant rs145763646 , associated with _SLC25A26_, a mitochondrial carrier protein, points to the role of cellular energy metabolism in binge eating susceptibility.^[1] Alterations in mitochondrial function can affect neuronal excitability and neurotransmitter synthesis, which are crucial for regulating appetite and impulse control . Variants like rs13233490 in _NXPH1_ (Neurexophilin 1), involved in neuronal communication, rs76087671 in the lncRNA _LINC01721_, and rs7337127 near the pseudogenes _ATP6V1G1P7_ and _RPL7P45_, collectively suggest that subtle genetic variations across diverse functional categories can converge to influence complex eating behaviors by affecting neural circuits, metabolic regulation, and gene expression.^[4]

Key Variants

RS ID	Gene	Related Traits
rs13233490	NXPH1 - GAPDHP68	binge eating
rs17810023	RPL17P25 - RPSAP72	binge eating
rs111940429	LINC01789 - LINC01885	binge eating
rs182107583	MMADHC-DT	binge eating
rs726170 rs6006893	ARHGAP8, PRR5-ARHGAP8	binge eating
rs145763646	SLC25A26	binge eating
rs76087671	LINC01721 - GAPDHP53	binge eating
rs10198175	LINC02850 - APOB	binge eating polyunsaturated fatty acid
rs7337127	ATP6V1G1P7 - RPL7P45	binge eating
rs73057489	RPL7P40 - PSMC1P8	binge eating

Defining Binge Eating: Core Concepts and Operationalization

Binge eating (BE) is primarily defined by the consumption of an unusually large amount of food within a discrete period, typically less than two hours, accompanied by a subjective sense of loss of control over eating.^[1] This core definition emphasizes both the objective quantity of food and the crucial psychological experience of being unable to stop or control what or how much is being eaten. Operational definitions in research contexts often specify these criteria, for instance, through direct questions about “food binges” involving rapid consumption and large amounts.^[1] However, the precise definition can vary across studies; some may employ a broader definition of BE, while others use more stringent criteria, necessitating careful consideration of the specific operationalization in any given research.^[1]The conceptual framework of binge eating encompasses both trait-like predispositions and episodic behaviors, often evaluated for either a “lifetime history” or “current” manifestation within a specified timeframe, such as the past six months.^[1]The subjective experience of “loss of control” is a critical component, distinguishing binge eating from mere overeating, and is typically assessed by asking individuals if they felt they “couldn’t stop eating or control what or how much they were eating” during such episodes.^[6]This nuanced understanding allows for the of binge eating behavior across different temporal windows and clinical presentations.

Classification and Diagnostic Frameworks

Binge eating is recognized as a transdiagnostic feature across various eating disorders, serving as a defining symptom for both Bulimia Nervosa and Binge Eating Disorder, and potentially occurring in Anorexia Nervosa.^[6]Within broader nosological systems, such as those guided by the DSM-IV criteria, binge eating can also delineate important clinical subtypes of other psychiatric conditions. For example, the presence of binge eating behavior in individuals with Bipolar Disorder (BD) is associated with a greater psychiatric and general medical burden, leading to its proposal as a distinct and significant BD subtype.^[1]The classification of binge eating can involve categorical approaches, determining a simple “yes/no” presence of the behavior, or dimensional assessments that capture severity and frequency. Diagnostic interviews like the Diagnostic Interviews for Genetic Studies (DIGS) and the Structured Clinical Interview for DSM-IV (SCID) are standard tools used to establish the presence of binge eating based on established clinical criteria.^[6]This sub-classification based on comorbid symptoms like binge eating is crucial for reducing phenotypic heterogeneity in genetic research and for tailoring clinical practice.^[6]

and Research Criteria

approaches for binge eating in research typically involve structured questionnaires and diagnostic scales designed to capture specific criteria. A common research criterion for lifetime history of BE involves a direct question such as, “Has there ever been a time in your life when you went on food binges (i.e., rapid consumption of a large amount of food in a discrete period of time, usually less than two hours)?”.^[1]For assessing current BE, instruments like the Eating Disorder Diagnostic Scale (EDDS) are employed, which include questions that operationalize both the quantity of food consumed (e.g., “unusually large amount of food”) and the subjective loss of control, typically over a recent six-month period.^[1]These tools establish thresholds and cut-off values for identifying the presence of binge eating, though the specific phrasing and recall period can lead to variations in definitions across different studies. Despite these differences, such as one sample defining BE as lifetime history of food binges and another as current eating of a large amount with loss of control in the last six months, research has shown that rates of BE behavior can remain comparable across samples.^[6]The consistent application of these criteria is vital for reproducible research and for understanding the genetic and environmental influences on binge eating.

Core Clinical Presentation

Binge eating is primarily characterized by consuming an unusually large amount of food within a discrete period, typically less than two hours.^[1] A defining feature of these episodes is a profound sense of loss of control over eating, where individuals feel unable to stop or regulate the amount consumed.^[1]This behavior is considered a trans-diagnostic feature, meaning it is a core symptom found across various eating disorders, notably as a defining criterion for bulimia nervosa and binge eating disorder, and it can also manifest in individuals with anorexia nervosa.^[1] The quantity of food is often described as what other people would regard as unusually large, such as a quart of ice cream, given the circumstances.^[1]

Assessment and Diagnostic Methods

The assessment of binge eating relies on both structured clinical interviews and self-report measures to capture its subjective and objective components. Diagnostic tools such as the Structured Clinical Interview for DSM-IV (SCID) and the Diagnostic Interview for Genetic Studies (DIGS) are employed to ascertain a lifetime history of binge eating behavior.^{[1], [6]} These interviews often include specific questions, such as inquiring about any past experiences of “food binges” defined by rapid, large consumption within a discrete period, usually less than two hours.^[1]Self-report instruments like the Eating Disorder Diagnostic Scale (EDDS) further aid in assessing current or recent binge eating patterns, typically within the past six months.^{[1], [8]} The EDDS specifically evaluates whether individuals have consumed unusually large amounts of food and experienced a loss of control during such episodes.^[1] While these methods primarily capture subjective experiences and self-reported behaviors, the consistency in rates observed across different assessment definitions (e.g., lifetime history versus recent behavior) suggests their diagnostic utility.^[1]

Phenotypic Diversity and Variability

Binge eating exhibits considerable phenotypic diversity and inter-individual variation, influenced by both genetic and environmental factors, with heritability estimated between 46% and 74%.^{[1], [3]}Definitions of binge eating can vary across studies, such as a lifetime history of food binges versus episodes occurring within the last six months, though these different approaches can yield comparable rates of behavior.^[1]

Diagnostic and Clinical Significance

The presence of binge eating holds significant diagnostic value, as it is a core symptom in several recognized eating disorders, aiding in differential diagnosis.^[1]Binge eating behavior co-occurs more often than expected by chance with conditions such as bipolar disorder, with reported prevalence in over 25% of individuals with bipolar disorder compared to 4.5% in the general population.^{[1], [2]}Clinically, binge eating is often correlated with greater psychiatric and general medical burden, particularly when it co-occurs with conditions like bipolar disorder.^[1]This comorbidity suggests that binge eating may represent an important clinical subtype, impacting overall illness severity and prognosis.^[1]Recognizing binge eating as a distinct clinical phenotype is crucial for both clinical practice and genetic research. Sub-classification based on such phenotypes, by reducing heterogeneity, can increase the power of genetic studies to identify specific risk factors, as demonstrated by genome-wide significant findings in relatively smaller samples.^[1]However, the interpretation of genetic associations in comorbid presentations requires careful consideration, as it may reflect risk for binge eating generally or for a specific subtype of the comorbid condition.^[1]

Causes

Binge eating is a complex trait influenced by a combination of genetic, environmental, and developmental factors, often interacting with one another. Research indicates that binge eating behavior is highly heritable, with genetic factors playing a significant role in its development.

Genetic Predisposition and Molecular Pathways

Binge eating behavior has a substantial genetic component, with heritability estimates ranging from 46% to 74%.^[1]Genome-wide association studies (GWAS) have begun to identify specific genetic regions and variants associated with binge eating, particularly when it co-occurs with other psychiatric conditions. For instance, single nucleotide polymorphisms (SNPs) in thePRR5-ARHGAP8 region, such as rs726170 , have shown a significant association with binge eating in individuals with bipolar disorder.^[1] The PRR5-ARHGAP8 gene produces a fusion protein where PRR5 is a subunit of mTORC2, a kinase involved in regulating food intake, and ARHGAP8 is a member of the RhoGAP family that mediates cellular signaling pathways.^[1] Further genetic investigations have implicated other genes, such as APOB, in the predisposition to binge eating, particularly within the context of comorbid bipolar disorder.^[6] Another notable finding includes a genome-wide significant association with SNP rs111940429 in an intergenic region near PPP1R2P5.^[1]While some candidate gene studies have suggested associations between binge eating and genes likeFTO in adolescents, HTR2A in young women, and NT5C1B in female twins, these specific findings have not always been consistently replicated across different studies.^[5] These genetic discoveries highlight potential biological mechanisms involving neural circuits related to appetite, reward, and impulse control.

Shared Genetic Architecture with Psychiatric Comorbidities

Binge eating frequently co-occurs with other psychiatric conditions, most notably bipolar disorder, at rates significantly higher than expected by chance.^[1]Approximately 25% of individuals with bipolar disorder experience binge eating, and this comorbidity is associated with a greater overall psychiatric and general medical burden.^[1] This strong association suggests a shared genetic architecture, where common genetic factors may contribute to the vulnerability for both mood dysregulation and disordered eating behaviors.^[6]Studying binge eating in the context of comorbidities, such as within a subtype of bipolar disorder, can help uncover specific genetic risk factors that might be challenging to identify otherwise.^[6]The observation that parental bipolar disorder increases the risk for eating disorders, including those involving binge eating, in offspring further underscores the potential for shared genetic influences across generations.^[1] This interplay between genetic predispositions for mood disorders and eating behaviors highlights the complexity of disentangling specific causal pathways, often suggesting gene-environment interactions where genetic vulnerability is expressed under certain conditions.

Environmental and Developmental Factors

Beyond genetics, environmental factors also contribute to the development of binge eating. While specific environmental influences like diet, lifestyle, or socioeconomic factors are not extensively detailed in all genetic studies, their general contribution alongside genetic determinants is recognized.^[1]These external factors can interact with an individual’s genetic predisposition to either trigger or exacerbate binge eating behaviors.

Developmental experiences, particularly during early life, can also play a role. The finding that parental mental illness is a risk factor for eating disorders in offspring suggests that the family environment, potentially encompassing both genetic transmission and early life exposures, influences vulnerability.^[1]This indicates that a combination of inherited susceptibilities and the developmental context in which an individual grows up can shape the risk profile for binge eating.

Genetic Predisposition and Gene Regulation

Binge eating (BE) is a heritable trait, with estimates suggesting that genetic factors contribute between 46% and 74% to its development. Similarly, bipolar disorder (BD), which frequently co-occurs with BE, exhibits a strong genetic component, with heritability estimated at 60-85%.^[1] This suggests a significant underlying genetic architecture influencing both conditions. Parental BD is also identified as a risk factor for eating disorders, including those involving BE, in offspring.^[6]Genome-wide association studies (GWAS) have begun to uncover specific genetic loci associated with BE, particularly in the context of BD comorbidity. One notable finding implicates single nucleotide polymorphisms (SNPs) in thePRR5-ARHGAP8 region, with rs726170 showing a genome-wide significant association with BE in BD cases.^[6] Another GWAS identified an association with APOB for BD patients with a history of BE.^[6] While candidate gene studies have previously suggested associations between BE and genes like FTO in adolescents or HTR2A in young women, and NT5C1Bwith bulimia nervosa spectrum, these specific findings were not consistently replicated in later, larger GWAS.^[6]

Molecular Signaling and Metabolic Pathways

The PRR5-ARHGAP8 gene, identified in association with BE, is a read-through transcript that produces a fusion protein.^[6] The PRR5component of this fusion protein encodes a subunit of mTORC2, a crucial serine/threonine kinase that plays a role in regulating food intake.^[6] The ARHGAP8 component is a member of the RhoGAP family of proteins, which are known to mediate intricate cross-talk between Rho GTPases and other vital cellular signaling pathways.^[6] These interconnected molecular pathways highlight potential mechanisms through which genetic variations could influence appetite control and cellular communication relevant to eating behaviors.

Further investigation into molecular pathways linked to BE has revealed the canonical Wnt signaling pathway as a top-ranked pathway in gene-set analyses comparing BD cases with and without BE.^[6] This pathway is fundamental for processes such as neurogenesis and neurodevelopment, plays a role in mood stabilizer action, and influences energy balance.^[6] The effector of the canonical Wnt signaling pathway, TCF7L2, has been identified as a network hub and is implicated in the genetic risk of BD with comorbid obesity.^[6] These pathways underscore the complex interplay of cellular functions and regulatory networks that contribute to both neurological function and metabolic control.

Neurodevelopmental and Homeostatic Disruptions

The co-occurrence of bipolar disorder and binge eating behavior is more frequent than expected by chance, suggesting shared underlying pathophysiological processes.^[6] This comorbidity is associated with a greater overall psychiatric and general medical burden compared to BD without BE. The observed genetic associations, such as those with PRR5-ARHGAP8 and APOB, may reflect a general risk factor for BE, a specific risk for BE in individuals with BD, or even define a distinct subtype of BD characterized by BE.^[1] This indicates a disruption in normal homeostatic mechanisms that regulate both mood and eating.

The involvement of pathways like the canonical Wnt signaling pathway points to potential neurodevelopmental processes that could be affected in individuals predisposed to BE and BD.^[6] Disruptions in these pathways could lead to altered neural circuitry involved in reward, impulse control, and emotional regulation, contributing to the recurrent episodes of uncontrolled eating. While the specific mechanism of action for identified genetic risk factors on these phenotypes requires further examination, the evidence points towards an underlying construct responsible for both mood disorders and eating behaviors.^[6]

Neurotransmitter and Inflammatory Systems

Beyond direct metabolic regulation, other systemic biological processes are implicated in binge eating. Gene-set analysis comparing BD cases with BE to controls revealed the cytokine-cytokine receptor interaction pathway as a top-ranking pathway.^[6] Cytokines, which are critical signaling proteins in the immune system, are known to play roles in the sickness response, often leading to suppressed appetite and inducing anhedonia.^[6]Dysregulation in this pathway could therefore contribute to altered appetite control and mood states, potentially exacerbating or precipitating binge eating episodes.

While not replicated in recent GWAS, prior candidate gene studies have explored the role of specific neurotransmitter systems, such as serotonin, through genes like HTR2A.^[6] HTR2Aencodes a serotonin 2A receptor, a key biomolecule involved in brain function, mood regulation, and appetite. The broader context of eating dysregulation traits associated with BD, along with the potential for shared genetic factors influencing both mood disorders and eating behaviors, underscores the intricate relationship between neurological, endocrine, and immune systems in the pathophysiology of binge eating.^[6]

Neurotransmitter and Intracellular Signaling Pathways

Binge eating behavior is linked to dysregulation within complex intracellular signaling networks, notably involving thePRR5-ARHGAP8 read-through transcript. This fusion protein combines PRR5, which encodes a subunit of mTORC2—a serine/threonine kinase crucial for food intake regulation—withARHGAP8.^[1] ARHGAP8 itself encodes a member of the RhoGAP family of proteins, which are instrumental in mediating intricate crosstalk between Rho GTPases and various other signaling pathways, thereby influencing cellular processes relevant to neuronal function and appetite.^[1] Furthermore, candidate gene studies have implicated the serotonin receptor HTR2Ain binge eating among young women, suggesting a role for neurotransmitter signaling in this complex behavior.^[1]

Metabolic and Energy Balance Regulation

Central to metabolic and energy balance regulation in the context of binge eating is the mTORC2 complex, whose subunit is encoded byPRR5, a component of the PRR5-ARHGAP8 fusion protein. This kinase plays a direct role in modulating food intake, making its dysregulation a critical factor in eating behaviors.^[1] Beyond direct food intake, the canonical Wnt signaling pathway has emerged as a top-ranked pathway, fundamentally involved in neurogenesis, neurodevelopment, mood stabilizer action, and the broader regulation of energy balance.^[1] Its key effector, TCF7L2, acts as a significant network hub and is associated with the genetic risk of bipolar disorder with comorbid obesity, underscoring the systemic integration of metabolic and neurological pathways.^[1] Additionally, the FTOgene, known for its strong association with obesity, has also been suggested as a candidate gene for binge eating in adolescents, indicating a direct link between genetic predispositions for metabolic traits and disordered eating.^[1]

Immune and Inflammatory Signaling Crosstalk

The cytokine-cytokine receptor interaction pathway represents another significant mechanism implicated in binge eating, particularly in individuals with comorbid bipolar disorder. This pathway was identified as a top-ranking pathway in comparative genomic analyses, suggesting its prominent involvement in the etiology of the condition.^[1]Cytokines are crucial mediators of the immune response, and their dysregulation can lead to a ‘sickness response’ characterized by profound physiological and behavioral changes. Specifically, altered cytokine signaling can induce suppression of appetite and lead to anhedonia, both of which can paradoxically contribute to disordered eating patterns or compensatory behaviors.^[1]

Genetic Susceptibility and Pathway Dysregulation

Genetic studies provide crucial insights into the underlying susceptibility and dysregulation of pathways contributing to binge eating behavior. Genome-wide association studies have identified significant associations between single nucleotide polymorphisms in thePRR5-ARHGAP8 region, such as rs726170 , and binge eating in individuals with bipolar disorder.^[1] Another significant association was observed at rs111940429 in an intergenic region near PPP1R2P5when comparing cases with bipolar disorder and binge eating to non-bipolar disorder controls.^[1] These genetic variants likely modulate the activity of the associated proteins, impacting their roles in food intake regulation and intracellular signaling crosstalk.^[1] Furthermore, other candidate genes like APOB, HTR2A, FTO, and NT5C1Bhave been implicated in binge eating or related eating disorder spectrums, suggesting that diverse genetic factors contribute to the multifactorial nature of binge eating by perturbing various metabolic, neurodevelopmental, and signaling pathways.^[6]

Prevalence, Comorbidity, and Heritability

Binge eating (BE), characterized by the rapid consumption of an unusually large amount of food within a discrete period, typically less than two hours, accompanied by a subjective sense of loss of control, is a transdiagnostic feature observed across various eating disorders.^[1] Epidemiological studies estimate its prevalence at approximately 4.5% in the general United States population.^[6] However, BE is significantly more common among individuals with bipolar disorder (BD), affecting over 25% of this population.^[6] This comorbidity with BD is associated with a greater overall psychiatric and general medical burden compared to BD without BE.^[9] Both BD and BE exhibit substantial heritability, underscoring a significant genetic component in their etiology. Bipolar disorder’s heritability is estimated to range between 60% and 85%.^[1] while BE itself has a heritability estimated between 46% and 74%.^[1] Research indicates that parental mental illness, including bipolar disorder, serves as a risk factor for the development of eating disorders, specifically those involving BE, in offspring.^[1] These epidemiological associations highlight the importance of investigating shared genetic architectures underlying the co-occurrence of BD and BE.

Large-Scale Cohort and Biobank Initiatives

Population studies on binge eating frequently leverage large-scale cohorts and biobank resources to explore genetic and clinical associations. The Genetic Association Information Network (GAIN) study of BD, for instance, included a substantial number of participants, comprising European American (N=2035) and African American (N=1015) subjects.^[6] Within this cohort, BE was ascertained based on a lifetime history of food binges, though this information was not consistently collected for control subjects, which posed a limitation for certain analyses.^[6] Further insights come from the Mayo Clinic Biobanks, which include the Mayo Clinic Individualized Medicine Bipolar Biobank and the Mayo Clinic Community Biobank.^[6]The Bipolar Biobank, a collaborative effort across multiple sites, enrolled 855 individuals with confirmed BD diagnoses based on DSM-IV-TR criteria, where BE was defined as a lifetime history of binge eating disorder determined by structured clinical interview.^[10]A separate analysis utilizing the Mayo Clinic Bipolar Disorder Biobank and Mayo Clinic Biobank controls for a genome-wide association study (GWAS) defined current BE using the Eating Disorder Diagnostic Scale (EDDS), identifying 192 cases of BE among 700 BD subjects with available EDDS data.^[6] These biobank-based studies are crucial for identifying specific genetic risk factors and understanding the complex interplay between BD and BE.

Methodological Approaches and Cross-Population Insights

Investigating binge eating at the population level requires robust methodological approaches to account for confounding factors and ensure generalizability. To address potential population stratification in genetic studies, researchers often restrict analyses to specific ancestry groups, such as focusing solely on European American subjects from the GAIN study, and employ statistical methods like principal components analysis.^[11] Control groups are typically matched for key demographic factors like gender and ethnicity to minimize spurious associations.^[12] A significant methodological consideration in population studies of BE is the variability in its definition across different datasets. For example, some studies define BE as a lifetime history of food binges.^[1] while others assess current BE within a specific timeframe (e.g., past six months) using diagnostic scales and criteria such as feeling a loss of control.^[6] Despite these definitional differences, the observed rates of BE behavior have been comparable across various samples.^[6] A common limitation in many of these studies is the lack of BE information for mentally healthy control subjects, which restricts the ability to determine whether identified genetic associations reflect a general risk factor for BE or are specific to a subtype of BD with BE.^[1]Furthermore, while initial studies have yielded genome-wide significant findings, the relatively small sample sizes in some analyses suggest that much larger cohorts are needed to fully elucidate the genetic architecture of binge eating and its comorbidities.^[6]

Frequently Asked Questions About Binge Eating

These questions address the most important and specific aspects of binge eating based on current genetic research.

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1. Why do some people never seem to binge, no matter what they eat?

Your genetics play a big role in susceptibility. Binge eating is highly heritable, meaning some individuals have genetic predispositions that make them more prone to it. Others may have protective genetic variations that make them less likely to experience a loss of control around food, even in challenging situations.

2. My mom has bipolar disorder; am I more likely to binge eat?

Yes, if a parent has bipolar disorder, you have an increased risk for developing eating disorders, including those involving binge eating. Both conditions are highly heritable, and there are shared genetic factors that can increase your susceptibility. It’s important to be aware of this family history.

3. I feel like my binge eating is different from what my friend experiences. Why?

Binge eating can have different underlying biological roots. For instance, if your binge eating is linked to conditions like bipolar disorder, specific genetic variants in regions likePRR5-ARHGAP8 or near PPP1R2P5 might be involved, which could make your experience unique compared to someone without those specific genetic influences.

4. Could my genes make it harder for me to control my eating when I’m stressed?

Your genetic makeup can certainly influence your body’s response to stress and food intake. Genes linked to binge eating, such as those in thePRR5-ARHGAP8region, are involved in pathways that regulate appetite and control. For individuals with these genetic predispositions, stress might more easily disrupt these pathways, making it harder to resist binge eating.

5. Does my binge eating mean I’m at risk for other health problems?

Yes, binge eating frequently co-occurs with other psychiatric conditions, notably bipolar disorder. This comorbidity is associated with a greater overall psychiatric and general medical burden. Understanding these connections, which often have shared genetic underpinnings like theAPOB gene, is crucial for your health.

6. Why do I feel like I totally lose control when I’m binge eating?

The feeling of losing control during a binge has a biological basis, partly influenced by your genetics. Genes like PRR5-ARHGAP8 are involved in regulating food intake and signaling pathways in the brain. Variations in these genes can affect your brain’s ability to signal satiety and control impulses, leading to that subjective loss of control.

7. If I have a family history of binge eating, will my kids definitely inherit it?

Not necessarily “definitely,” but they will have an increased genetic predisposition. Binge eating is highly heritable (46-74%), meaning genes play a significant role. Your children will inherit a mix of your genes, so while the risk is higher, environmental factors and other genes will also influence whether they develop the behavior.

8. Is my binge eating just a bad habit, or is there a deeper reason I can’t stop?

It’s often much deeper than just a habit; there’s a strong biological and genetic component. Binge eating is a highly heritable condition, and specific genetic variants have been identified that influence brain pathways related to food intake regulation and impulse control. This means there are biological mechanisms at play beyond willpower.

9. Why do some diets work for others but not for my binge eating?

Your genetic makeup can influence how your body responds to food and dietary interventions. Genetic factors contribute significantly to binge eating and its comorbidity with other conditions. This means a “one-size-fits-all” approach may not work, as your unique genetic profile might require a more tailored strategy to address the underlying biological drives.

10. Can exercising regularly help overcome my genetic predisposition to binge eating?

While exercise is beneficial for overall health, simply exercising might not fully “overcome” a strong genetic predisposition to binge eating. Genetic factors contribute significantly to the condition’s heritability (46-74%), influencing brain pathways related to appetite and control. However, a healthy lifestyle, including exercise, can still be a valuable part of a comprehensive management plan.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] McElroy, S. L. et al. “Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.”Translational Psychiatry, vol. 8, no. 1, 2018, p. 40.

[2] Hudson, J. I. et al. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol. Psychiatry 61, 348–358 (2007).

[3] Lichtenstein, P. et al. “Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study.”Lancet, vol. 373, no. 9659, 2009, pp. 234–239.

[4] Bould, H. et al. “Parental mental illness and eating disorders in offspring.” International Journal of Eating Disorders, vol. 48, no. 3, 2015, pp. 383–391.

[5] Micali, N. et al. Are obesity risk genes associated with binge eating in adolescence? Obesity 23, 1729–1736 (2015).

[6] Winham, S. J. et al. “Bipolar disorder with comorbid binge eating history: A genome-wide association study implicatesAPOB.” Journal of Affective Disorders, vol. 165, 2014, pp. 151–158. PMID: 24882193.

[7] “Genetic Landscape of Bipolar Disorder and Comorbidities: A Comprehensive Review.” Biological Psychiatry.

[8] Krabbenborg, M. A. et al. “The eating disorder diagnostic scale: psychometric features within a clinical population and a cut-off point to differentiate clinical patients from healthy controls.”European Eating Disorders Review, vol. 20, no. 4, 2012, pp. 315–320.

[9] McElroy, S. L. et al. “Clinical features of bipolar spectrum with binge eating behaviour.”Journal of Affective Disorders, vol. 201, 2016, pp. 95–98.

[10] McElroy, S. L. et al. Bipolar disorder with comorbid binge eating: a review of the literature. J. Affect. Disord. 147, 1-13 (2013).

[11] Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

[12] Smith, E. N. et al. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol. Psychiatry 14, 755–763 (2009).