The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa

Dopamine has long been implicated as a critical neural substrate mediating anorexia nervosa (AN). Despite nearly 50 years of research, the putative direction of change in dopamine function remains unclear and no consensus on the mechanistic role of dopamine in AN has been achieved. We hypothesize two stages in AN– corresponding to initial development and entrenchment– characterized by opposite changes in dopamine. First, caloric restriction, particularly when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. Second, chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of now established AN behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility. If correct, our hypothesis has significant clinical and research implications for AN and other disorders, such as addiction and obesity.

Cognitive Behavioural Therapy for an Adolescent with Anorexia Nervosa

Introduction: The treatment of anorexia nervosa remains a matter of much debate. Though cognitive behavioural therapy would seem to offer good results, there is still no resounding evidence pointing to a single treatment of choice. The case presented in this paper examines the treatment with CBT of a patient presenting anorexia nervosa. Evaluation/diagnosis: An adolescent girl, 17 years of age, voluntarily attends psychological therapy to address eating behaviour problems. After administering the EAT-26, EDI-2, and BSQ standardised screening tests, as well as a clinical interview for assessment, a psychopathological profile is obtained, providing a diagnosis of anorexia nervosa, restricting subtype. Therapeutic goals: The therapeutic goals set were to reach a healthy weight for the patient’s age and height (specified as a minimum BMI of 18.5) and change the structure of thoughts, feelings, and behaviour that was justifying and maintaining the disorder. Treatment: Treatment lasted for 33 sessions and used cognitive behavioural techniques, such as cognitive restructuring, response cost, and positive reinforcement, in addition to family intervention techniques. Nutrition therapy was also carried out in parallel to the treatment sessions. Results: Following eight months of weekly sessions, the patient reached the target weight and changed attitudes towards food and body image, replacing them with healthy thoughts and behaviours. Follow-up made one and two years after the end of the treatment saw that these results were maintained. Discussion and conclusions: In this case, CBT proved effective in achieving the patient’s physical and psychological recovery. Therefore, this case contributes to the evidence of the efficacy of this therapeutic approach in certain cases of ED.

Genome-wide DNA methylation profiling in anorexia nervosa discordant identical twins

Up until now, no study has looked specifically at epigenomic landscapes throughout twin samples, discordant for Anorexia nervosa (AN). Our goal was to find evidence to confirm the hypothesis that epigenetic variations play a key role in the aetiology of AN. In this study, we quantified genome-wide patterns of DNA methylation using the Infinium Human DNA Methylation EPIC BeadChip array (“850 K”) in DNA samples isolated from whole blood collected from a group of 7 monozygotic twin pairs discordant for AN. Results were then validated performing a genome-wide DNA methylation profiling using DNA extracted from whole blood of a group of non-family-related AN patients and a group of healthy controls. Our first analysis using the twin sample revealed 9 CpGs associated to a gene. The validation analysis showed two statistically significant CpGs with the rank regression method related to two genes associated to metabolic traits, PPP2R2C and CHST1. When doing beta regression, 6 of them showed statistically significant differences, including 3 CpGs associated to genes JAM3, UBAP2L and SYNJ2. Finally, the overall pattern of results shows genetic links to phenotypes which the literature has constantly related to AN, including metabolic and psychological traits. The genes PPP2R2C and CHST1 have both been linked to the metabolic traits type 2 diabetes through GWAS studies. The genes UBAP2L and SYNJ2 have been related to other psychiatric comorbidity.

Effects of autism on 30-year outcome of anorexia nervosa

Background Long-term consequences of comorbid autism spectrum disorder (ASD) in individuals with anorexia nervosa (AN) are inadequately investigated. Methods In the 1980s, 51 adolescent-onset AN cases (AN group) and 51 matched controls (COMP group) were recruited from the community. They have been examined on five occasions. The four last assessments included the Morgan-Russell Outcome Assessment Schedule (MROAS) to assess eating disorder outcomes (weight, dieting, menstruation), and related problems including psychiatric, psychosexual and socioeconomic state. In the present study, at age 44, when 30 years had elapsed, MROAS data were compared with previous results. At age 16, 21, 24 and 32 years, all individuals had been assessed regarding ASD. At the 30-year follow-up, the impact of the ASD on the MROAS data was analysed. Results In the AN group, all core anorectic symptoms (weight, dieting, menstruation) were on a par with the COMP group at the 30-year follow-up, but the positive outcomes were limited to those who had never had an ASD diagnosis. Psychiatric state was significantly worse in the AN group, particularly in the subgroup who had an ASD diagnosis assigned. The AN group—again particularly those with ASD—had a more negative attitude to sexual matters than the COMP group. The AN group had worse outcomes than the COMP group for ‘personal contacts’, ‘social contacts,’ and ‘employment record’ at the 30-year follow-up and the outcomes were worse the more often an ASD diagnosis had been assigned. Limitations Rare data collection points throughout 30 years (only 5 assessments). ASD was assessed in the first four studies but was not assessed again at the 30-year follow-up. Conclusions Mental health, psychosexual, and socioeconomic status were compromised up to 30 years after AN onset. Coexisting ASD contributed to the poor outcome. Core anorectic symptoms had “normalised” three decades after AN onset. Plain English summary Some individuals with anorexia nervosa (AN) also suffer from autism. In this study we have investigated outcome of AN 30 years after the onset of AN and whether the presence of autism affects the outcome. Since the 1980s we have followed 51 individuals with teenage-onset AN and 51 healthy controls. They have been examined on five occasions, and an instrument that measures symptoms of AN (weight, dieting, body image), psychiatric symptoms, ability to work, and relationships with partner, family, and friends has been used to assess outcome. Autism was assessed in the first four studies. Symptoms of AN had normalised at 30-year follow-up, but only among those without autism. Psychiatric symptoms, ability to work, and relationships were issues that persisted after 30 years in the AN group, and those who had both autism and a history of AN had even more pronounced problems in these areas. The AN group had a more negative attitude to sexual matters than the control group, the outcome was worse the more often an autism diagnosis had been assigned. Conclusions Mental health, psychosexual, and socioeconomic status are affected up to 30 years after AN onset, particularly among those with autism.