Even when the temporal stages of a psychiatric disorder cannot be so clearly delineated, it can be helpful to split diagnoses into endophenotypes that are associated with the disease of interest. For example, a recent GWAS of insomnia, which is a core symptom of multiple psychiatric disorders and a DSM criterion for MDD, identified 202 loci and showed strong genetic correlations with MDD and several other psychiatric conditions . Similarly, neuroticism, which shares a common genetic basis with MDD but can be more easily measured, could serve as a clinical stratifying factor for antidepressant actions. However, it can be difficult to determine what level of dissection is required; a recent study suggested that neuroticism reflected two genetic dimensions, one capturing depressed affect, and another capturing worry. Another example comes from several GWAS of impulsive personality, which has been proposed as an endophenotype for several psychiatric disorders including ADHD. The UPPS-P is a self-reported questionnaire that measures 5 different aspects of impulsive personality. Only two of those five were significantly associated with ADHD; in contrast, all three sub-scales of BIS-11, which is another impulsive personality questionnaire, were significantly associated with ADHD35. These examples illustrate how disease phenotypes can be dissected into component parts. Nonetheless, despite the original claim that endophenotypes would have a simpler genetic architecture, all studies conducted to date have shown that both disease diagnoses and endophenotypes are highly polygenic. Once the traits that reflect domains of normal function have been measured in genotyped cohorts,vertical grow racking system it becomes possible to explore their empirical relationships with one another beyond those that are already defined by traditional psychiatric nosology .
Genomic SEM and related techniques are now being used in a number of such efforts. Luningham et al used genomic SEM to test multiple models of psychopathology among fourteen psychiatric disorders and related traits. They identified three factors , and an uncorrelated Neuro developmental Disorders factor. These factors showed distinct patterns of genetic correlations and accounted for substantial genetic variance. These empirically identified clusters may provide better targets for GWAS than individual disorders. In another example, Baselmans et al showed that it was possible to increase power by using Genomic SEM to integrate multiple traits into a measure of “well-being spectrum”. By aggregating data from different sources of correlated traits, they reached a sample size of over 2.3 million individuals, which allowed them to identify 304 independent signals associated with well-being; a similar analysis suggested a two factor model that distinguishes “lower end” and “higher end” well-being factors. In a third example, Thorp et al used Genomic SEM to identify two factors, which they referred to as “psychological” and “somatic” from the 9-item Patient Health Questionnaire . Recently, several related methods have been developed . Using RGWAS, Dahl et al55 proposed a stress subtype in MDD, and identified three novel sub-types of metabolic traits. Using BUHMBOX , Han et al found that seropositive and seronegative rheumatoid arthritis could be subdivided to form a new subgroup within seronegative-like cases. Conversely, they identified a genetic correlation between MDD and SCZ, but there was no evidence that this correlation was due to subgroup heterogeneity.Clumping has been used to test the hypothesis, originally suggested by twin studies, that psychiatric disorders share a single common genetic factor. One of the earliest studies to use GWAS data to test this hypothesis showed that SNPs associated with schizophrenia were also associated with bipolar disorder.
Specific genes have been identified that confer risk for multiple psychiatric disorders . Evidence that the risk for substance abuse is shared across multiple substances is also consistent with earlier results from twin studies showing both substance-specific and substance-independent genetic risk. An example of this genetic overlap is the gene CADM2, which has been associated several substances and risky behavior. Joint analysis of correlated traits may outperform that of single phenotypes and allows the possibility to disentangle genetic effects that are specific to each trait from those that capture a latent construct . Clumping can also lead to new splits. For example, Bansal et al used GWAS results from two correlated traits: schizophrenia and educational attainment to propose two distinct etiologies of schizophrenia, one that resembled bipolar disorder and was characterized by high education, and another that reflected a cognitive disorder and was independent of education. Studies like this one provide greater flexibility to explore the phenotypic space, which can lead to novel insights and challenge established nosologies.Throughout this perspective, we have alluded to GWAS producing novel biological insights; however GWAS have numerous limitations and do not themselves produce actionable new knowledge. The influence of locus on a phenotype may be due to a coding difference or a regulatory difference.Indeed, a recent meta-analysis indicated that among those with ED, the lifetime prevalence rate of a comorbid SUD was 21.9% . Tobacco, caffeine, and alcohol are reported as the most prevalent SUDs for individuals with EDs . Sedatives, cannabis, stimulants, and over-the-counter products such as laxatives, diuretics, and diet pills are also commonly abused . Research suggests that ED patients with co-occurring SUDs experience lower rates of treatment response, higher relapse rates, more severe medical complications, greater impairment, poorer long-term outcome, and are at higher risk of early mortality . Given the high-risk nature of individuals with co-occurring EDs and SUDs , and poor outcomes associated with their treatment, it is important to identify whether effective treatment interventions for this population.
A major barrier to identifying treatment targets for ED-SUD is the paucity of research comprehensively characterizing the treatment-seeking ED-SUD patient population. Below, we outline the existing literature characterizing ED-SUD and associated features.Separately, EDs and SUDs have the highest and second-highest mortality rates of all psychological disorders . Both EDs and SUDs often present with comorbid mood disorders, anxiety disorders, post traumatic stress disorder , and borderline personality disorder . Becker and Grilo found that among patients with binge eating disorder , those with both mood and substance use disorders had the most severe ED symptoms, and higher rates of personality disorders. In a retrospective chart review, Kirkpatrick et al. found that for adolescents with ED, those with comorbid SUD had higher rates of self-harm and purging, and had a higher BMI at intake. Finally, a small study of an inpatient sample showed that those with ED-SUD were more likely to be diagnosed with a Cluster B personality disorder compared with those with ED alone . ED Diagnosis. Several studies have investigated whether co-occurring SUD is more common in anorexia nervosa-restricting type , anorexia nervosabinge-purge type , or bulimia nervosa . Theoretically, it is believed that binge-purge behaviors are more closely linked to substance abuse, as there is evidence for an increased association between these behaviors and impulsivity and emotion regulation difficulties . One large study found that within ED patients, BN, and AN-BP patients had the highest prevalence of comorbid substance use, whereas AN-R participants generally had the lowest . Root et al. found that across eating disorder groups,vertical growing cannabis the BN and AN-BP groups were more likely to report alcohol abuse and diet pill use relative to the AN group, and the AN-BP group was more likely than the AN-R group to have alcohol abuse, use diet pills, stimulants, and engage in poly substance abuse. Along the same lines, Fouladi et al. found patients with BN used substances with higher frequencies compared to patients with ANR, BED, and EDNOS, and those with AN-BP were more likely to use substances than those with AN-R. Moreover, higher frequencies of binge eating and purging were associated with higher frequencies of substance use. Finally, a meta-analysis on this topic by Bahji et al. revealed that prevalence rates of SUD were significantly higher among individuals with binge-purge behaviors than those with only restrictive behaviors.Temperament and underlying emotion regulation difficulties serve as common risk and maintenance factors for EDs and SUDs. Recent research provides compelling support for theories of emotion regulation to explain the co-occurrence of disordered eating and substance abuse . Specifically, these theories posit that individuals engage in these maladaptive coping strategies to alleviate negative affect . In support of this, existing findings indicate that affective instability, impulsivity, negative urgency, and novelty seeking are common in individuals with EDs who engage in substance abuse .
For example, a study investigating temperament found that binge eating was associated with increased impulsivity and risky decision-making . Similarly, in a study of undergraduate men and women, researchers found that negative urgency, a component of emotion dysregulation that includes the tendency to act rashly when distressed, was significantly associated with problematic alcohol use and disordered eating . Finally, Loxton and Dawe found that adolescent girls who abused alcohol and engaged in disordered eating were more sensitive to reward than adolescent girls who did not engage in any of these behaviors. Overall, extant literature highlights the complex nature of ED-SUD presentations. Thus, traditional treatment programs have targeted EDs and SUDs sequentially. However, interest in integrated treatment approaches has grown , and research indicates that patients who do not receive integrated treatment have poorer treatment outcomes . Nevertheless, there is limited research on what such an integrated approach should optimally target, and there is no consensus in the field about the best treatment modality for the ED-SUD population. One potentially promising intervention for ED-SUD is Dialectical Behavior Therapy , which is a treatment based on an emotion regulation model . In DBT, psychoeducation on this model is provided, and patients are encouraged to accept and learn to tolerate their emotional experiences, while also learning alternative methods of coping with their emotions. DBT is a well-established treatment for individuals with multiple and severe psychological disorders , and has been adapted for use with EDs . Its further adaptation and testing for individuals with co-occurring SUDs and BPD support its use to target multiple problem areas in an integrated manner. Only one study has investigated the application of DBT for co-occurring EDs and substance use. Findings from this study are promising, suggesting that integrated DBT for EDSUD treatment is associated with decreased substance use severity and frequency, decreased emotional eating, and increased levels of confidence in ability to resist urges for substance use . Given the limited research on DBT for ED-SUD, a better understanding of factors associated with ED-SUD compared to ED or SUD alone may be helpful in identifying potential treatment targets to address both disorders simultaneously. The impetus for the current study was to add to this limited literature by reproducing previous research findings in a treatment-seeking ED population and discussing how these empirical findings can guide treatment recommendations for ED-SUD. Consequently, the present study examined differences between patients with EDs only to patients with ED-SUD on demographics, psychiatric comorbidity, and self-reported eating disorder and related psychopathology. Given previous research findings, we hypothesized that individuals with EDSUD would be more likely than ED only to engage in binge eating/purging, and to have a bulimic-spectrum eating disorder, BPD symptoms, higher rates of psychiatric comorbidities, self-harm, and suicidality, greater difficulties with emotion regulation, and more reward sensitivity.Participants with ED only and ED-SUD were compared on demographic variables, comorbidities, psychotropic medications, and self-report measures at treatment admission. Categorical variables were compared using chi-square analyses and continuous variables were compared using one-way analyses of variance. To control for multiple comparisons, the threshold for significance was set at p = .01. Values below the threshold of p < .05 are discussed as trends, given the exploratory nature of the analyses and limited data on this topic to date.The present study sought to describe differences between ED patients with and without a SUD at treatment admission. Results demonstrated that ED-SUD patients reported a greater number of comorbid psychiatric diagnoses and were more likely to be prescribed mood stabilizers. They also reported greater difficulty engaging in goal-directed activity, higher impulsivity, more limited access to emotion regulation strategies, and higher reward sensitivity. There were trend-level differences suggesting that individuals with ED-SUD were more likely to engage in objective binge episodes, be diagnosed with panic disorder and post traumatic stress disorder, and to report higher trait anxiety, global emotion dysregulation, and sensitivity to punishment.