Psychosis In Anorexia Nervosa: A Case Report and Review of the Literature

Introduction

Anorexia nervosa (AN) is a psychiatric disorder characterized by restriction of energy intake relative to requirements, fears about weight gain or behavior that interferes with weight gain, and disturbances in one’s perceptions about one’s body or shape. (1) The illness impacts approximately 1.4% of women, and 0.2% of men, with a bimodal age of onset with peaks during late adolescence and young adulthood. (2, 3) Adults often present with gradual but substantial weight loss and can show little insight about the etiology of their weight loss. (4) Although a common perception is that individuals with AN must overvalue shape or weight, the actual diagnostic criteria only require a persistent lack of recognition of the seriousness of the current low body weight. (1) Patients that are unaware or deny that body-image concerns contributed to weight loss may not be evaluated for an eating disorder, delaying appropriate treatment.

In contrast, an acute psychotic episode resulting in hospitalization is more commonly referred for psychiatric evaluation. The lifetime prevalence of psychotic disorders is approximately 3%, with 0.21% due to medical conditions and 0.42% due to illicit substances, and the peak age of onset is also in young adults.(5) Importantly, malnutrition can contribute to psychosis through many pathways. Both specific nutritional deficiencies, including niacin, thiamine, and vitamin B12, and complications common during malnutrition, such as sleep deprivation and metabolic derangements, are known medical causes of psychosis. Diagnosis of a primary psychotic disorder should be made only after nutritional rehabilitation has occurred so that other medical causes are excluded. Here we report a case where the diagnosis of AN was delayed due to the presence of psychotic symptoms, and provide a literature review covering cases of co-occurring psychosis in the presentation of AN.

Case Report

Ms. K, a 22-year-old black female, with no past medical or psychiatric history, presented for evaluation of weight loss and refusal to eat. Her mother reported changes in eating behaviors for the prior six months with a 13.6 kg weight loss. Ms K had recently graduated from a 4-year college and planned to move across the country to initiate employment. Ms K stated that the “voice of God” told her to not eat. She prayed constantly because she had pain in her body and could not determine if the source was “God or the enemy”. On exam, she was extremely thin (body weight 35.7 kg; height: 167.6 cm; body mass index [BMI]: 12.7), pale and withdrawn with psychomotor delay and minimal eye contact. Her first admission was to medicine for leukopenia and bradycardia. Work-up for infectious or malignant etiologies was negative. After receiving fluid and electrolyte repletion for mild hypokalemia (potassium 3.1 mmol/l) and acute kidney injury (creatinine 1.1 mg/dl), she was discharged five days later with follow-up in the psychiatric clinic. She refused initiation of any psychiatric medications.

Six days after discharge her mother brought her back to the ED for refusal to eat or drink anything. She was too weak to care for herself. During this second admission, she continued to have poor food intake and expressed uncertainty about further psychiatric treatment related to eating behaviors. She was discharged after two weeks because the medical team believed she was regressing in the hospital environment, exhibiting manipulative and attention seeking behavior.

Ms. K arrived for an outpatient psychiatric appointment four weeks later, and her weight had dropped an additional 2.7 kg (32.2 kg; BMI: 11.5). Because she now reported an indifference to dying and remained fixated on the belief that God told her not to eat, she was involuntarily admitted to the psychiatric unit. During her third hospital stay and first on a psychiatric floor, she struggled to characterize how God communicated with her, sometimes describing thoughts in her head or God speaking only to her. Her exam was notable for latency of speech, apparent thought blocking and frequent sudden staring episodes. She was started on olanzapine 2.5 mg at bedtime, and that was increased to twice a day for her psychosis. She reported that olanzapine didn’t help with the thoughts in her head. She continued to struggle with food intake and was witnessed chewing food and then spitting it out.

During this third admission, Ms. K was transferred from psychiatry to medicine because of medical complaints consistent with malnutrition: constipation, cold hands and feet, chest pain, dysuria, and multiple episodes of hypoglycemia. The two weeks spent on the psychiatric unit for involuntary treatment of new onset psychosis had resulted in an additional weight loss of 1.4 kg (30.8 kg; BMI: 11.0). On physical exam she had proximal muscle weakness requiring assistance to stand up from a seated position as well as acrocyanosis of her hands and feet. Even minimal exertion such as sitting up or speaking would cause her to go from bradycardia to tachycardia. A nasogastric tube was placed on day 14 of this hospital stay because of her physiological decompensation from malnutrition. Her oral intake was monitored with food logs and nasogastric feeds were adjusted such that her total caloric intake was started at 1400 calories and increased by 400 calories every 4 days.

Two weeks after initiation of nasogastric feeding her weight had increased to 41.3 kg. Once feeding began, she gradually became more interactive with reduced response latency, spontaneous dyadic conversations, and more elaborate responses. Olanzapine was increased to 7.5 mg daily to help with sleep and ruminating thoughts about food. She began drinking and eating food at meal times as well, but only after the hospital staff, including physicians, nurses, dietitians, and sitters, both supervised and enforced completion of meals on the medical floor. She reported anger towards the staff at this time, but attributed the anger to olanzapine, not the enforced changes to her eating or weight gain. She stopped hearing God talk to her but denied that his absence was bothersome. In therapy, she became more goal directed. Her daily routines became less rigid and she became more in touch with her physical needs, taking naps or sleeping in as needed.

In her early interactions with physicians and therapists, Ms. K reported a strong interest in religion during childhood but denied any visions or auditory hallucinations. She stated that she began hearing God speak to her about one year ago, after her boyfriend broke up with her. She believed God was directing her to not eat as punishment for her sins of sexuality outside of marriage. At this time, her weight was approximately 63.5 kg. She reported making a choice to become vegan and lose weight, and had installed a health app on her phone. She lost 4.5 kg in three months and stopped menstruating. Ms. K also described how her food restriction then became more systematic. She eliminated specific types of foods, choosing to only eat one type of item, such as soups, avocados, or cereal for days. She stopped eating almost entirely the week before her initial admission. Although she was able to recall these events with prompting, she lacked insight about how her food restriction contributed to her hospitalization.

After 4 weeks, weighing 45 kg, she was transitioned to nocturnal tube feeds only with 3 meals and boost plus four times per day. Two days later tube feeds were stopped entirely as she was able to eat >75% of her meals and snacks. Her insight and judgment had significantly improved. She advocated for herself during a therapy session, stating she was hungry and needed a snack. She set her own goal to become more comfortable eating in front of others, and had awareness that eating with others was difficult for her. She acknowledged a tendency to isolate herself and difficulty forming friendships throughout her life. She attributed this in part to her perfectionism and propensity to self-blame. Recognizing that her previous job offer might be a trigger for her eating disorder as it would be in a different city away from social support, she agreed to continue therapy at a residential eating disorder treatment facility.

After 6 weeks at a residential eating disorder treatment center, she returned home. Olanzapine was tapered off and her weight remained stable at her baseline 61.2 kg (BMI 21.8). Although she remained devout in her religious beliefs, she no longer reported hearing God directly. She was not bothered by this, and had become engaged in work-life activities.

Discussion

Psychotic episodes occur in 10–15% of eating disorder patients. (6) The prevalence of primary psychotic diseases like schizophrenia and schizoaffective disorders in eating disorder patients appears to be comparable to that in the general population. (7) To determine if specific features of presentations may assist in the differential diagnosis of psychosis and AN, we searched PubMed, MEDLINE, and PsychInfo with terms (psychosis or psychotic) and (anorexia nervosa or eating disorders). Cases of bulimia nervosa, orthorexia nervosa or review articles on the topic were excluded. Twelve cases of co-occuring psychosis and eating disorder symptoms were identified; this case is also summarized in Table 1. In nine of the other cases, the patients were severely underweight at presentation, and at the lower end of normal BMI in the remaining three. Restriction was predominant eating behavior, with purging in four cases. Auditory hallucinations were the most common psychotic component, present in seven cases. Ms K as well as the cases in our literature review highlight the difficulty in determining the etiology of psychosis in the setting of malnutrition, and also provide evidence about differences in treatment responses for these disease processes. Our presumptive diagnosis and rationale based on the evidence presented for each case is summarized in the far right column of Table 1.

Table 1.

Brief Review of Cases of Psychosis and Eating Disorder Behaviors and Low Body Mass

First Author	Age/Sex	BMI	Psychotic Symptoms	Eating Disorder Cognitions and Behaviors	Psychotropic Treatment (Medications)	Clinical Course and Treatment	Presumptive Diagnosis and Rationale
Brodrick, B. (This Article)	22/F	11.0	Auditory hallucinations – religious command to not eat	Restriction	Olanzapine	See text. One year history of progressive restriction of food and rapid weight loss, with increasing religious beliefs progressing to command auditory hallucination to not eat.	Anorexia Nervosa: eating symptoms preceded psychosis and psychosis resolved after nutritional rehabilitation
Delsedime, N. (14)	29/F	9.9	Delusions including mystic, omnipotence, and persecution features	Restriction, over exercise	Olanzapine	12 year history of eating behaviors prior to hospitalization. During the 2nd week she developed psychotic features such as loosening of associations, tangentially, persecutory ideas and marked perceptual alterations. Delusions improved with olanzapine; discharged at BMI 11.9.	Undetermined: eating symptoms precede psychosis so possible eating disorder but full weight restoration not obtained
Dodig-Curkovic, K (15)	15/F	14.5	Ambivalence regarding suicide, delusions and possessed ideas about external physical appearance	Restriction	Escitalopram, Fluvoxamin, Supiride, Olanzapine, Valproate	1.5 year history of eating behaviors prompting first hospitalization. Sulipiride and olanzapine initiated outpatient for mental deterioration and weight loss. Ten months later she was hospitalized a 2nd time due to worsening physical condition and psychosis. Resolved and discharged on olanzapine and valproate. Two months later, BMI had increased to 17.	Eating Disorder: eating symptoms preceded psychosis; delusions focused on physical appearance
Imran, N. (16)	12/M	16.3	Auditory hallucinations, odd behaviors, paranoid delusions, and multiple suicide attempts	Restriction, fear of weight gain, body image distortion	Olanzapine, Escitalopram	Symptoms began 1 year prior with aimless wandering and extremely limited diet. He subsequently reported auditory and visual hallucinations. He believed the voices were eating his brain. Family refused admission but agreed to pharmacologic treatment. Ultimately he was lost to follow-up.	Both – psychotic symptoms and disorganization coincide and precede eating; delusions more pronounced and less consistent with eating disorder ideas
Kiraly, B. (17)	23/M	20	Suicidal ideations, bizarre delusions, no auditory or visual hallucinations	Restriction, purging, over exercise	Fluoxetine, Olanzapine	6 month history of eating behaviors. One month into treatment he developed acute psychotic episode. Psychosis rapidly improved with olanzapine 10mg BID. One month later after stopping his medications he had a psychotic episode with bizarre delusions. He was lost to follow-up at 6 months.	Both – psychosis and eating appear to have separable timelines, and psychosis very responsive to olanzapine and separate from eating behaviors
Lyon, M (18)	14/F	15.3	Delusions and auditory hallucinations	Restriction, fear of weight gain, body image distortion	Not specified	Mild mental retardation as a result of traumatic brain injury at age 3. One month history of extreme food refusal and 2 year history of undetected psychosis. After 8 week hospitalization during which she was treated with psychotherapy and psychotropic medications, AN resolved and schizophrenia began to respond to medications.	Both – psychosis and eating have different timeframes and responses to medication and therapy
Moga, DE. (8)	42/F	13	Auditory hallucinations, thought insertion, paranoid delusions	Restriction, purging	Risperidone, Olanzapine, SSRI	History of AN binge/purge since high school. 3 years prior to admission she joined evangelical Christian church. She started fasting because she felt judged by God. She received behavioral therapy, psychotherapy and pharmacotherapy including initiation of atypical antipsychotic while hospitalized. Her symptoms improved and she was discharged at over 90% of her ideal body weight.	Eating disorder – psychotic symptoms are only present during severe eating disorder, with psychosis closely related to overvalued eating ideas
Rojo-Moreno, L. (19)	14/F	14	Auditory hallucinations	Restriction, fear of weight gain	Risperidone	8 month history of eating behaviors. One week after hospitalization reported male voice commanding her not to eat. After initiation of risperidone, voices gradually disappeared and she was symptom free at discharge.	Eating Disorder – psychotic symptoms limited to severe eating disorder timeframe, and related to overvalued eating ideas
Rojo-Moreno, L. (19)	18/F	16.4	Auditory hallucinations	Restriction	Risperidone	1 year history eating behaviors. During 2nd week of admission she complained of hearing voices that she perceived as external to herself with content relating to her fears. After 1.5 months of psychological and pharmacologic (risperidone and SSRI) treatment, she was asymptomatic and discharged.	Eating Disorder – psychotic symptoms are congruent with eating disorder and limited to expression of ideas that oppose eating disorder
Sarro, S. (20)	22/F	18.9	Auditory hallucinations	Restriction, over exercise, fear of weight gain, body image distortion	Sertraline, Olanzapine, Diazepam	8 year history of eating behaviors prior to entering day treatment program for recent decline. Several previous hospitalizations with auditory hallucinations. Restarted on intensive psychotherapy and pharmacologic therapy. Psychosis had not reappeared at follow-up but cognitive rigidity remained.	Eating Disorder-psychotic symptoms only present during eating disorder
Thorpe, M. (9)	19/M	17.7	Paranoid delusions, thought distortion, command hallucinations	Restriction, over exercise	Risperidone	After a 1 year history of eating behaviors he developed paranoid delusions prior to first hospitalization. Symptoms remitted with risperidone. 3 months later after stopping his antipsychotic medications he developed psychosis again with hallucinations and delusions that were distortions of his previous anorexic symptoms.	Both – Eating symptoms precede reported delusions but psychosis recurred rapidly even when nourished

Moga and colleagues (8) describe a case with many similarities to Ms. K. A 42 year old woman with a long history of AN, binge/purge type became convinced God was prohibiting her from eating. She believed God communicated with her directly in her thoughts, with bible passages, and in other people’s words. She prayed for hours and repented her sins, compulsively tracked in a notebook. Anxiety and psychotic symptoms diminished and insight improved in this patient shortly after initiation of antipsychotics. Psychosis and religious scrupulosity were in the differential for both this case and our own. Scrupulosity refers to behaviors or thinking in which individuals are overly attentive to religious rituals. Inconsistent with scrupulosity, the beliefs about food restriction for both patients were not commonly practiced within their religious community. In both cases their religious rituals intensified with weight loss and their compulsive behaviors improved with weight restoration, further demonstrating the importance of nutritional rehabilitation prior to establishment of a psychiatric diagnosis.

Cognitive processes in AN are more commonly described as overvalued ideas and ruminations, whereas cognitive disturbances in psychosis are often characterized as delusions and hallucinations. Psychotic symptoms were dominated by ideas about eating, body shape, and weight in all cases in this review. Importantly, there are no objective rules that distinguish an overvalued idea from a delusion and patients’ reports of internal symptoms such as hallucinations may be similar to ruminations. Many eating disorder patients will refer to ruminations and distorted beliefs about eating, food, and their body as their “eating disorder voice”. When Mountjoy and colleagues (4) compared body image distortions in AN to delusions in schizophrenia, they found individuals with AN reported higher distress about their beliefs than those with schizophrenia but were comparable in their conviction and disruption ratings. Thirty percent of the AN participants also showed low insight about their cognitive disturbances. Moreover, both AN and schizophrenia share neurocognitive deficits: difficulties in shifting attention, overestimation of detail, and weak central coherence. Acute clinical and cognitive symptoms may be insufficient to differentiate AN from primary psychotic disorders because both can present with low insight, similar neurocognitive deficits, and overvalued ideas.

Restriction serves as an emotional numbing agent so often anxiety intensifies with acute nutritional intake in AN. In addition, many patients with primary eating disturbances will experience increased anxiety as immediate physical discomfort after eating, a cycle that promotes more restriction. In contrast, the benefits from improved nutrition for memory, emotional processing and cognition may take weeks to observe. Nasogastric feeding can allow a more continuous source of nutritional intake for patients that are unable to consume sufficient calories orally due to emotional and physical distress. As Ms K’s weight increased, auditory hallucinations resolved and anxiety about eating diminished. Relatively quickly, she achieved the required caloric intake with meals and oral nutritional supplementation, and nasogastric feeding was tapered off. Concomitantly, she became aware of the emotional and psychosocial stressors contributing to the onset of her psychiatric symptoms. In contrast, cases where a primary psychosis process occurred can have worsening of psychotic symptoms with nutritional rehabilitation. (9) Disorganization became more prominent with feeding, a stark contrast to the highly rigid and ritualized behaviors seen in AN. Hugo and Lacey have postulated that eating restriction may be a defense mechanism to manage the disorganization of psychosis, emphasizing the need to obtain a history with a detailed chronology of symptoms to ascertain the order of psychiatric symptoms.(10)

In all cases, improvement in psychiatric symptoms occurred after initiation of antipsychotics. Hyperactivity, a common symptom in AN, can overcome dopamine pathway deficits present during starvation in AN rodent models, suggesting dopamine deficiency may be involved in the perpetuation of AN behaviors. (11) Further support for dopamine pathway involvement in AN is that olanzapine modestly improves weight restoration in adult outpatients with AN. (12) Therefore a positive response to antipsychotic medications does not necessarily confirm the presence of a primary psychotic disease. Dopamine signals are critical for both learning and motivation in animal models. (13) Thus, dopamine pathways may be crucial for executing the behavioral changes required for recovery from AN.

Our case as well as the others identified in the literature underscore the complexities in deciphering the etiology of psychosis in the setting of malnutrition. Nutritional rehabilitation was key to unraveling the etiology of the psychotic symptoms. After weight restoration, patients with AN, akin to Ms. K, are likely to have resolution of psychosis whereas patients with a primary psychotic disorder may require additional antipsychotic medications. Weight restoration should not be delayed while waiting for psychotic symptoms to respond to antipsychotics, as any delay can result in further physical deterioration, as demonstrated by Ms K. AN should remain high on the differential when delusions and hallucinations are related to food intake or body image.