Comorbidity of anorexia nervosa and schizophrenia: A systematic review

Abstract

Research on the intersection between eating disorders and schizophrenia has mainly focused on binge eating, since increased appetite and metabolic side effects are common during antipsychotic use. However, the prevalence of restrictive eating and anorexia nervosa may be higher in people with schizophrenia than in the general population, and evidence suggests shared genetic liability for schizophrenia and anorexia nervosa (AN). The aim of this systematic review was to examine the prevalence, psychological and biological mechanisms, and theoretical underpinnings underlying the co-occurrence of AN and schizophrenia. We identified 42 articles that met inclusion criteria. Evidence suggested that the prevalence of AN in patients with schizophrenia is higher than would be expected in the general population; conversely, evidence regarding the prevalence of schizophrenia in AN was mixed. Psychological mechanisms underlying AN in people with schizophrenia fell into three categories: positive symptoms, negative symptoms, and atypical pathways. A limited literature generally supports the hypothesis of higher prevalence of AN in patients with schizophrenia, but there are few studies in this area. Studies of the prevalence of schizophrenia in AN yield more mixed finding, although these studies are also relatively small and few. Further, studies of both types tend to include only clinically-ascertained samples, which limits the generalizability of findings beyond patients. Larger, better-designed studies may improve identification and treatment of people with co-occurring schizophrenia and anorexia nervosa.

1. Introduction

Research on disordered eating in SCZ has focused largely on binge-eating disorder (BED), since antipsychotics can cause increased appetite and weight gain (Kluge et. al., 2007; de Beaurepaire, 2021), which is a risk factor for development of cardiometabolic issues. However, the prevalence of other forms of disordered eating in people with SCZ is less well studied. Evidence from genome-wide association studies and reports of clinical comorbidity suggest that restricted eating may also affect a subset of people with psychosis (Watson, 2019; Zhang, 2023). Although restriction is common in all eating disorders, it is the hallmark of anorexia nervosa (AN). Individuals with AN can also experience psychotic symptoms either secondary to their AN or malnutrition (e.g. truly believing that touching food leads causes weight gain), or as the result of a co-occurring psychotic disorder. Additionally, the mechanisms by which AN and psychosis may co-occur are unclear. With clinical emphasis focused largely on identifying binge eating and weight gain associated with the use of antipsychotics, it is possible that restrictive eating behaviors are overlooked until symptoms become acute. Since AN can lead to serious medical complications and carries a high suicide risk, awareness of prevalence, risk factors, and early signs, are necessary to identify individuals who are beginning to restrict their food intake (Mehler et. al., 2022;. van Eeden et. al., 2021).

The goal of this review was to examine the phenomenon of co-occurring AN and SCZ. Here we systematically review the prevalence of comorbidity between AN and SCZ, and we examine biological and psychological mechanisms that may be associated with comorbidity.

2. Methods

This systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines.

Search Strategy

The search was conducted using PubMed and APA PsychInfo. The following search terms were used: ‘schizophrenia’ AND ‘anorexia,’ ‘schizophrenia’ AND ‘anorexia nervosa,’ ‘prevalence of anorexia and comorbid schizophrenia.’ Reference sections of selected papers were also reviewed to identify relevant articles.

Inclusion/Exclusion Criteria

Articles were included if they included participants with symptoms of both SCZ and AN, were in English, were empirical articles, reviews, or case reports. Articles that include disorders other than SCZ and AN and report findings separately by participants with SCZ and AN were excluded. Articles that included multiple eating disorders were included if they specified the number of individuals with AN. RH (1) conducted the searches and decisions about inclusion/exclusion, and this search was independently screened by KEL (2) using the same methods. Any discrepancies in inclusion/exclusion decisions were resolved by discussion and consensus.

3. Results

Study Characteristics and Risk of Bias

1,176 articles were identified based on our search, of which 39 met inclusion criteria (see Figure 1). Of the 39 studies included, 18 were case reports or case series. As case reports and case series have a small sample size by definition, there is a high likelihood that there is bias in our sample; however, the Joanna Briggs Institute (JBI) critical appraisal tool, a checklist to assess bias in case reports, was used. Significant bias was not found in the case reports.

Figure 1.

See Tables 1–3 for descriptions of all articles

Table 1.

Included case studies

Author(s)	Year	Country	Summary points
Andrew, M., & Harris, B.	1994	UK	A 54-year-old woman met criteria for both AN and SCZ. She had religious delusions and hallucinations that resulted in fasting and praying. She also had body image disturbance. She didn’t respond to antipsychotics, ECT, or behavioral interventions.
Brodrick BB, Jacobs MA, McAdams CJ	2020	USA	A 22-year-old black woman presented with weight loss and food refusal in the context of "the voice of God" telling her not to eat due to the sin of sexuality outside marriage. She decompensated nutritionally and required medical intervention for nutritional rehabilitation. After she was no longer malnourished, she no longer experienced the auditory hallucination.
Cinemre B, Kulaksizoğlu B. Olgu Sunumu: Bir Erkek Hastada Anoreksiya Nervoza ve Sizofreni Eşhastalanimi	2007	Turkey	A 14-year-old boy developed AN and went on to develop SCZ at 18. Olanzapine caused weight gain which caused ED to go untreated as the patient was at a normal weight. When psychotic symptoms were reduced, the patient lost weight.
Crișan C, Androne B, Barbulescu LD, Suciu BD	2022	Romania	A 44-year-old woman developed AN at 15 and SCZ at 22. She was admitted medically at 22 at which point she divulged that she was hearing voices and had elevated scores on the PANSS. The voices took on AN themes and never related to food being poisoned. She was prescribed olanzapine and the voices abated partly and she gained 2 kg but still struggled with her body image.
Dadić-Hero E, Ružić K, Grahovac T, Valković T, Petranović	2011	Croatia	A 38-year-old woman with chronic SCZ and significant weight loss in the context of worsening negative symptoms to be considered by a doctor to have “anorexic syndrome,” though she did not meet full criteria for AN. She was given olanzapine which resolved both the symptoms of SCZ and AN.
Grounds, A.	1982	UK	Over the course of 1961–1980 there were 7 cases of transient psychosis in individuals with AN. In almost all cases, psychosis started after the patients were admitted to the hospital and resolved in between 1–12 weeks of onset. All cases involved positive symptoms.
Hugo PJ, Lacey JH	1998	UK	Case 1: A 17-year-old woman with AN and a family history of SCZ rehabilitation started having delusions of reference and auditory hallucinations after some nutritional rehabilitation. Antipsychotics were started and symptoms abated. When she stopped medication, the AN recurred and psychotic symptom returned during weight restoration. Case 2: A 19-year-old woman with AN (B/P) had 2-year history of social withdrawal, self-harm, and alcohol use. When she was admitted, she endorsed the delusion of a blocked intestinal tract and denied distress about weight. Her writing indicated that she used her ED to escape psychotic thoughts. She was diagnosed with SCZ.
Imran N, Rumesa F, Jamil F	2018	Pakistan	A 12-year-old Pakistani boy developed command auditory hallucinations, food refusal due to fear of gaining weight, and low mood all in the same year. He was diagnosed with separate SCZ and AN along with depressive symptoms due to his food refusal not explained by content of hallucinations. Notably he made a suicide attempt resulting from both command hallucinations and his parents urging him to eat.
Kelly, L., Kamali, M., & Brennan, T.	2004	Ireland	There were 4 patients who presented with adolescent AN but later received diagnoses of SCZ. Negative symptoms that were previously attributed to ED were then attributed to SCZ and AN was considered the prodrome. Case 1: A 20-year-old male who was diagnosed with AN at 15 developed psychosis at 16. He heard voices that often commented on his fatness and ugliness. The AN waxed and waned but the psychotic and negative symptoms remained constant. Case 2: A 15-year-old male was admitted to inpatient program, presented as socially withdrawn and became paranoid that his food was poisoned. Antipsychotics were started which reduced delusional beliefs and helped with ED behavior (restriction, binging/purging), but aloof manner continued. Case 3: A 14-year-old girl admitted for treatment became aggressive, socially withdrawn and self-harming. She had delusional beliefs about the food. Paranoia reduced with antipsychotics as did ED behaviors. Case 4: A16- year-old adolescent with a 2-year history of AN, which had improved after a previous hospitalization, now came following an overdose in response to hallucinations calling him “fat and ugly.” He was socially withdrawn had manneristic behavior and required no further treatment for AN but needed antipsychotics to control his auditory hallucinations.
Kiraly B, Joy EA	2003	USA	A 23-year-old male triathlete developed AN and disorganized thinking, which led to a brief psychotic disorder. When he went of his antipsychotics, the psychosis re-emerged and he was diagnosed with SCZ.
Lai H, Tan S.	2014	Malaysia	A 13-year-old girl who was diagnosed with early onset SCZ developed AN along with binge eating and vomiting. The content of her voices became more food related and she viewed her binge eating as the result of an external force. She was switched from olanzapine to quetiapine to reduce binge eating episodes. She engaged in treatment with her family and achieved remission.
Lyon, M. E., & Silber, T. J.	1989	USA	A 14-year-old girl presented with weight loss and food refusal in the context of body image disturbance. She had an intellectual disability due to a head injury. The Diagnostic Interview Scale for Children revealed that her eating disorder cognitions were the result of psychosis and she was diagnosed with SCZ. She was hospitalized and treated with psychotherapy and medication.
Moga, DE, Cabaniss DL, Marcus ER, Walsh BT, Kahn DA	2009	USA	A woman with a history of AN since high school became intensely religious and began withholding food due to it. She thought that if she ate, God would get angry and give her a heart attack. Her doctors came to the conclusion that this was a delusion outside of her religious beliefs and not the result of scrupulosity OCD.
Rojo-Moreno, L., Plumed, J. J., Fons, M. B., Gonzalez-Piqueras, J. C., Rojo-Bofill, L., & Livianos, L.	2011	Spain	Two individuals with AN had auditory hallucinations with themes of food that resolved with antipsychotic treatment and nutrition.
Salmon, G.	1996	UK	Case 1: A 21-year old who was diagnosed with AN at 12 exhibited bizarre behavior during re-feeding and was treated with antipsychotics. She returned with olfactory hallucinations and accompanying delusions. At age 32, she deteriorated with psychosis and social functioning and her delusions revolved around eating others. She then stared binging and engaging in rumination. Case 2: A woman presented at 19 saying that her older sister was trying to poison her food. She had also lost interest in food but denied dieting. At 20, she was admitted after an overdose and severely underweight but thought she was overweight. Three years later, she had another overdose and was binging and purging. At age 27, she had auditory hallucinations saying that she had killed her mother. She was treated with ECT for depression but continued to have delusions that her stomach was rotting and that she could smell it as well as that she had swallowed devils who were trying to eat her from inside because she was a bad person. She was treated with clozapine but worried about weight gain and increased binging/purging while other symptoms improved. Case 3: A girl presented with at AN 15. She denied dieting but later said that she wanted to lose weight to become sick. She gained weight with family work but was re-admitted for weight loss and flat affect was noted. At 19, she was admitted for severe weight loss: regressed, uncommunicative, hostile. She eventually weight restored, but depression treatment didn’t work. She Came back at age 20 with auditory hallucinations and no eating pathology and dx with SCZ.
Wenokur B, Luby ED	1997	USA	A 41-year-old woman denied AN saying that restrictive eating was the result of allergies and feeling of choking due to “drainage” in her neck. Antipsychotics failed or were not tolerated and she was prescribed clomipramine which helped her to gained weight which continued upon discharge. Months later she started worrying about gaining too much weight and AN was diagnosed.
Yamashita Y, Takei N, Kawai M, Mori N.	1999	Japan	A 14-year-old girl with AN was medically hospitalized and received intravenous nutrition. The AN symptoms vanished and were replaced by psychosis. Antipsychotics resolved the psychosis but negative symptoms persisted.
Yum SY, Caracci G, Hwang MY	2009	USA	Case 1:A 53-year-old man with SCZ was preoccupied with keeping his weight at a certain place. He often put vinegar on his food which he believed helped him maintain his weight. Case 2: A 43-year-old woman with SCZ who refused to eat due to delusions; as starvation continued her delusions became increasingly bizarre in nature. These symptoms resolved with antipsychotics and re-feeding. Case: 3: A 50-year-old man with SCZ and strong negative symptoms and depression punished himself by not eating. Case 4: A 29- year-old women who had been a model before her SCZ diagnosis exhibited restrictive eating behaviors along with positive symptoms. Sometimes her body image concerns became grandiose and delusional in nature, however after her positive symptoms improved, the body image and food preoccupation continued.

Table 3.

Included reviews

Author(s)	Year	Country	Summary points
Bou Khalil, R., Hachem, D., & Richa, S.	2011	Lebanon	Men with SCZ appear to have a greater likelihood of AN than women. Those who struggle fall into the following categories: psychosis caused by malnutrition, prodromal ED, SCZ onset pre-ED, and medication induced ED.
Kouidrat, Y., Amad, A., Lalau, J. D., & Loas, G.	2014	France	This focuses on other EDs of for the most part but mentions that men are 3.6 times more likely to have both AN and SCZ and that the frequency of AN in SCZ is between 1–4%.
Morylowska-Topolska, J., Ziemiński, R., Molas, A., Gajewski, J., Flis, M., Stelmach, E., & Karakuła-Juchnowicz, H.	2017	Poland	This review examines the reciprocal relationships between AN and SCZ looking at the prodromal period, during remission of psychotic episodes, and over the course of acute AN.
Poletti, M., Preti, A., & Raballo, A.	2022	Italy	This review examines disembodiment as a transdiagnostic factor between EDs and SCZ. The author focuses on how people with EDs can have attenuated psychotic symptoms that cross the border between clinical high risk and first episode.

Prevalence of Comorbidity

Of the seventeen empirical studies included, eight reported evidence of higher comorbidity than would be expected based on prevalence in the general population for each disorder and one reported evidence of lower comorbidity (Binder, 2006; Striegel-Moore et. al., 1999; Malaspina et. al., 2019; Miotto, 2010;; Shiraishi et. al., 1992; Ferguson and Damluji, 1988; Hsu, 1981; Zhang, 2023) (See table 2). AN has a lifetime prevalence of 1% and SCZ about 0.53% in the US (Hudson et al., 2007; Udo and Grilo, 2018; Wu et. al.,2006), whereas prevalence of AN in SCZ ranged from 0.56% to 36% in these reports, and prevalence of SCZ in AN ranged from 0% to 5.2% (Malaspina et. al., 2019 ; Miotto, 2010; Striegel-Moore et. al., 1999; Zhang et. al., 2023). In addition, two reviews found that, despite AN being significantly more common in women, men were significantly more likely to have both AN and SCZ (Bou Khalil, 2011; Koudirat; 2014).

Table 2.

Included empirical studies

Author(s)	Year	Country	Purpose	Sample size	Summary Points
Blinder, B. J. , Cumella, E. J. & Sanathara, V. A.	2006	USA	to assess psychiatric comorbidities of inpatients with eating disorders	520 AN-R, 436 AN-B	SCZ was 3 times as likely in AN-R and twice as likely in AN-B/P compared with other EDs. Ten out of 2436 had a comorbid psychotic disorder.
Ferguson, J.M. and Damluji, N.F.	1988	USA	to assess symptoms of individuals with SCZ and AN	200 AN, 12 SCZ and AN	The 12 cases of AN and SCZ were examined. In this small population, negative symptoms were more pronounced than positive symptoms and they deteriorated more with their AN.
Goldstein M. J.	1981	USA	to compare the family environments of individuals with AN and SCZ	65 families	The SCZ families exhibited more communication difficulties and negative affect while the AN families showed more dependency.
Hsu, G., Metzler, E., Crisp, A.	1981	UK	to assess patients attending a hospital for the co-occurrence of SCZ and AN	6 AN	Between 1968 and 1972 105 female patients at a British hospital were assessed for AN and SCZ and 5 were diagnosed with them.
Hudson, J. I., Pope, H. G., Jr, & Jonas, J. M.	1984	UK	to assess the etiology of psychosis in individuals with AN and BN	6 AN and psychosis	The individuals with AN all had affective psychosis and not SCZ.
Jones E, Watson JP	1997	USA	to examine the difference between overvalued ideas in AN, delusions in SCZ as compared with religious beliefs in healthy controls	20 SCZ, 20 AN, 20 controls	Delusion was differentiated from overvalued idea in truthfulness, acceptability, imagination, use of perception, and use of thought. Overvalued idea and control beliefs were similar except that overvalued ideas influenced behavior and cognition. Delusions were thought about more frequently, were more important and had greater capacity to influence behavior than control beliefs. Delusions were more about conviction and AN overvalued ideas more about associations and implications.
Lu, Z. A., Ploner, A., Birgegård, A., Eating Disorders Working Group of the Psychiatric Genomics Consortium, Bulik, C. M., & Bergen, S. E.	2024	Sweden	to examine the shared genetic components of AN and SCZ through a GWAS study	53,386 SCZ, 16,992 AN	There were 69.9% concordant effect directions among shared variants of AN and SCZ. Ten shared loci between the two disorders were identified between the two disorders with high expression in the hippocampus during adolescence and the orbitofrontal cortex during infancy.
Lysaker, Paul H ; Chernov, Nikita ; Moiseeva, Tatyana ; Sozinova, Marta ; Dmitryeva, Nadezhda ; Makarova, Anastasiya ; Kukla, Marina ; Myers, Evan ; Karpenko, Olga ; Kostyuk, Georgiy	2023	USA	to test differences in levels of alexythymia, emotion recognition and metacognition across AN, schziophrenia spectrum disorders (SSD) and BN and examine levels of general psychopathology and eating disorder behaviors across these groups	53 SSD, 40 AN	Metacognition was most deficient in the SSD group, though the AN group displayed greater deficit than the BN group. The AN group had the most difficulties with alexithymia and the SSD group had poorer emotion recognition than the eating disorder groups. High levels of alexithymia were only related to eating disorder behaviors in the BN group and metacognition in the AN group. Deficits in emotion recognition was related to all PANSS components in the SSD group and metacognitive deficits were related to higher levels of negative symptoms.
Malaspina, Dolores ; Walsh-Messinger, Julie ; Brunner, Anna ; Rahman, Nadia ; Corcoran, Cheryl ; Kimhy, David ; Goetz, Raymond R. ; Goldman, Sarah Bellovin	2019	USA	to use a secondary analysis to compare SCZ groups with and without eating disorders	288 SCZ	9.4% of the 288 individuals with SCZ had an eating disorder and 5.2% had AN with or without BN. The eating disorder group had increased positive and disorganized symptoms with more gustatory hallucinations, higher anxiety and depression, and higher IQ than the individuals without eating disorders (though these were more likely to have nonverbal score deficits.) The eating disorder group had similar functioning and negative symptom scores to the non-eating disorder group.
Miotto, P., Pollini, B., Restaneo, A., Favaretto, G., Sisti, D., Rocchi, M. B. ., & Preti, A.	2010	Italy	to assess the prevalence of psychosis in AN and BN	61 AN 631 controls	Though patients with AN scored higher on some psychosis items, no patients with AN were found to have comorbid SCZ.
Mountjoy RL, Farhall JF, Rossell SL	2014	Austrailia	using the PSYRATS and BABS, determine the differences between overvalued ideas in AN to body dissatisfaction in healthy controls to delusions in SCZ	20 AN, 27 SCZ, 23 controls	Participants with AN were more likely to have insight and attribute thoughts to psychiatric origin than SCZ patients but they also have higher distress and preoccupation with their beliefs (only 10% AN rated to the delusional intensity.) Both had similar ratings in conviction and disruption.
Powers, P. S.	2005	USA	to summarize the results of a study in which the PANSS was used in a sample of participants with AN	39 AN, 240 SCZ	Over 70% of AN participants had some positive symptoms. 28 of 39 AN participants had evidence of delusions and 27 had evidence of suspiciousness. There was also significant overlap in negative symptoms and AN patients scored higher on depression.
Shiraishi, H., Koizumi, J., Suzuki, T., Yamaguchi, N., Mizukami, K., Hori, M., & Tanaka, Y.	1992	Japan	to assess SCZ in individuals hospitalized with eating disorders at a university hospital	21 AN, 5 AN and SCZ	This retrospective report from a university hospital between 1977 and 1991 found 21 individuals with AN and of those, 5 had SCZ as well as AN.
Small, A. C., Madero, J., Gross, H., Teagno, L., Leib, J., & Ebert, M	1981	USA	To compare individuals with SCZ and individuals with AN on the MMPI	14 SCZ, 14 AN	MMPI scores across subscales did not significantly differ between individuals with AN and SCZ.
Striegel-Moore RH, Garvin V, Dohm FA, Rosenheck RA	1999	USA	to examine comorbidities with eating disorders in a sample of hospitalized male veterans	25 AN	Of the veterans with AN, 36% of them had comorbid SCZ.
Watson, H. J., Yilmaz, Z., Thornton, L. M., Hübel, C., Coleman, J. R. I., Gaspar, H. A., Bryois, J., Hinney, A., Leppä, V. M., Mattheisen, M., Medland, S. E., Ripke, S., Yao, S., Giusti-Rodríguez, P., Anorexia Nervosa Genetics Initiative, Hanscombe, K. B., Purves, K. L., Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan, R. A. H., Alfredsson, L., … Bulik, C. M.	2019	USA	To examine the genome loci that determine AN risk	16992 AN	SNPs in this GWAS showed that SCZ, AN, and other metabolic markers such as type 2 diabetes and HDL cholesterol were on similar loci.
Zhang R, Kuja-Halkola R, Birgegård A, Larsson H, Lichtenstein P, Bulik CM, Bergen SE	2023	USA	to examine familial coaggrigation of EDs and SCZ and evaluate how this shapes clinical outcomes	12424 AN	Looking at AN specifically, 4.8% of individuals had family history of SCZ (up to third degree relatives.) 0.56 % had comorbid SCZ. Having a first degree relative SCZ was associated with great comorbidity of ADHD, SUD, anxiety disorders, higher lowest BMI, SCZ in any relative with AN associated with higher somatic and mental health burden but lower ED psychopathology scores.
Zhang, R., Larsen, J. T., Kuja-Halkola, R., Thornton, L., Yao, S., Larsson, H., Lichtenstein, P., Petersen, L. V., Bulik, C. M., & Bergen, S. E.	2021	USA		12863 AN, 3146 SCZ	This study found that individuals with any eating disorder have 6–7 times the risk of having SCZ. For AN specifically, they found an association between siblings but not parents.

Binder and colleagues (Binder, 2006) completed a study of 2,436 eating disorder inpatients where they found that individuals with AN-restricting subtype (n=520, 10 with a co-occurring psychotic disorder) had a 3 times greater chance of having a psychotic disorder than were those with other ED diagnoses with a prevalence of about 1.9%. Additionally, a study of male veterans hospitalized at 155 VA hospitals determined that of 466,590 patients, 25 were diagnosed with AN, and, of those, 36% had comorbid SCZ (Striegel-Moore et. al., 1999). One study assessed comorbid AN in people with SCZ, finding that of 288 people who were psychiatric inpatients diagnosed with SCZ, 5.2% met criteria for lifetime history of AN. Additionally, this study found that those with premorbid or prodromal eating disorders experienced higher positive and disorganized symptoms, higher anxiety and depression, and higher IQ scores (Malaspina et. al., 2019). Several studies using retrospective chart review found elevated prevalence of comorbid illness. One study found that 23.8% of patients with AN in a university hospital in Japan had SCZ (Shiraishi et. al., 1992). Six percent of patients with AN at a United States clinic had SCZ (Ferguson and Damluji, 1988). In a study of hospitalized patients in the UK, 5.7% of females were diagnosed with both SCZ and AN (Hsu, 1981). Lastly, a population-based study from Sweden and Denmark examining co-aggregation of AN and SCZ found that the rate of SCZ was elevated in probands with AN relative to people without AN or any other eating disorder diagnosis. Further, relatives of probands with AN also demonstrated higher rates of SCZ, with odds generally decreasing with decreasing genetic relatedness (Zhang et. al., 2023).

However, a study examining symptoms of psychosis in people with AN found that while 46.7% of participants endorsed 2 or more psychotic symptoms on the SCL-90R symptom dimensions “paranoid ideation” as compared with 27.3% of healthy controls, out of a sample of 61, none of the AN patients met full criteria for a psychotic disorder (Miotto, 2010).

Biological mechanisms

There were three genome-wide association studies as well as family studies. These studies suggest possible shared genetic contributions to SCZ and AN. A genome wide association study found that AN loci were associated with SCZ in the same places that correlated with metabolic concerns like Type 2 diabetes and high cholesterol (Watson et. al., 2019). One study found that 4.8% of individuals with AN have a history of SCZ in up to a third degree relative. Having a relative with SCZ was associated with increased mental health burden overall but lower eating disorder psychopathology scores (Zhang et. al., 2023). Associations between AN and SCZ also holds true for siblings (Zhang, 2021).

Psychological Mechanisms

There is also evidence of distinct psychological factors in AN and SCZ with five empirical articles examining these. Mountjoy et. al. examined the blurred boundary between over-valued ideas in AN and delusions in SCZ by comparing beliefs in AN to body dissatisfaction in healthy controls to delusions in SCZ measured by conviction, preoccupation, distress, and action. While patients in the SCZ group were more likely to experience delusions and have low insight (10 out of 27 individuals as opposed to 2 out of 20 individuals), those with AN were more likely to have higher distress and preoccupation with their beliefs (Mountjoy et. al., 2014). A 2018 study by Edgar and Jones separated beliefs into initial, or observational beliefs and derived or non-observational beliefs. They study found that, as expected, overvalued ideas were more likely to be derived beliefs, involving thought beyond perceptions whereas delusions were more uniquely perceptual (Edgar and Jones, 2018).

In addition, another study examined metacognition and alexithymia across AN and SSD. Metacognition was most deficient in the SSD group, though the AN group displayed greater deficit than the BN group. The AN group had the most difficulties with alexithymia and the SSD group had poorer emotion recognition than the eating disorder groups (Lysaker, et. al., 2023). Another study showed that AN and SSD groups didn’t significantly differ on dimensions of the MMPI (Small et. al., 1981). Still another found that the families of individuals with AN versus SCZ had distinct pathology (Goldstein, 1981).

Despite the distinct psychological mechanisms underlying AN and SCZ, many individuals with these disorders co-occurring experience delusions with content about food and body image disturbance. The case studies detailed below in which positive symptoms emerged exemplify this. Some of the psychotic experiences, like voices commenting on their bodies, cut close to the phenomenon called the “anorexic voice,” where a voice that a patient with AN feels is outside of themself is telling them their eating disorder thoughts (Powers, 2005). However, other aspects of the psychotic experiences seem to align more with typical delusions in SCZ such as poisoned food or the belief that there are devils in one’s rotting stomach.

It must be noted that individuals with solely AN do, in some cases, exhibit positive symptoms. A 2005 study compared AN and SCZ patients’ scores on the Positive Negative Syndrome Scale (PANSS) and found that the SCZ group scored higher on the positive symptom scale than the AN group (19.9 as opposed to 12.3.) However, over 70% of the AN patients had some positive symptoms (Powers, 2005). A few examples of this appear in case studies where individuals with AN experience auditory hallucinations or other psychotic symptoms that remit with nutritional rehabilitation in inpatient eating disorder treatment (Rojo-Moreno et. al, 2011; Brodrick et. al., 2020). Similarly, a case series reported transient psychosis lasting no longer than 12 weeks in individuals with AN (Grounds, 1982).

Case Reports

Eighteen case reports and case series examining AN in individuals with SCZ met criteria for inclusion. Of the 27 individual cases described, the majority exhibited AN in the context of positive symptoms of psychosis, 2 in the context of negative symptoms of psychosis, 2 had atypical presentation, and 3 presented with AN in the setting of desire to reduce weight, although with some possible delusional ideation in two cases (see table 1).

Religious themes were noted in several cases. In one, a 54-year-old woman believed that God had instructed her to fast, and, in another, a 22-year-old woman heard the voice of God telling her not to eat (see table 1)(Andrew and Harris, 1994; Brodrick et. al., 2020). Although these cases had similar presentations, the former did not respond to ECT, antipsychotics or behavioral interventions, whereas the latter improved with both olanzapine and nutritional rehabilitation.

Other delusional themes were found in 3 other cases. A woman stopped eating because she reported not wanting to be immortal, and nasogastric feeding had to be employed until she received olanzapine and the delusion subsided (Yum et. al., 2009). Other types of delusions have also been attributed to severe restricting including delusions that food had been poisoned (Kelly et. al., 2004).

In four cases auditory, somatic, or olfactory hallucinations were associated with AN. A case series reported patients hearing voices commenting on their bodies (Kelly et al., 2004). One report found that a patient experienced somatic hallucinations of food ripping through her stomach, and another patient reported believing that she had swallowed devils and could smell her stomach rotting from inside out (Sarró et. al., 2009; Salmon et. al., 1996). Lastly, a 50-year-old man experiencing a guilt delusion reported punishing himself by not eating (Yum et. al., 2009). Though this case does not meet full criteria for AN, his restriction was purposeful and notably disordered.

In two cases, AN emerged in the context of severe negative symptoms. In one report a 38-year-old woman with SCZ refused food due to lack of energy, interest, and appetite to the point that she was diagnosed with an “anorexic syndrome.” Although she did not meet criteria for AN due to her weight loss not being intentional, her restrictive eating led to significant health risk (Dadić-Hero et. al., 2011). Another case report described adolescent girl who was admitted for weight loss that she attributed to wanting to become sick. She also had a flat affect and was “regressed, uncommunicative, and hostile.” Positive symptom onset occurred later during adulthood. (Salmon et. al., 1996).

Two case studies reported atypical cases that do not fully fit in AN or SCZ categories with their patterns of delusions and food refusal. A 41-year-old woman was described as having a “somatic delusional disorder,” in which she did not eat due to self-described allergies and feelings of choking that she attributed to sinus drainage in her neck. Clomipramine was prescribed and she gained weight. A few months later, however, she reported that she thought she was gaining too quickly and discontinued the medication thereby losing weight, at which point she was diagnosed with AN (Wenokur and Luby, 1997). Additionally, a 12-year-old boy developed auditory hallucinations, low mood, and food refusal concurrently, and was diagnosed with SCZ and AN (Imran et. al., 2018). This was the only case report identified in which SCZ and AN onset concurrently.

In several cases patients with SCZ developed AN or restrictive eating in the setting of motivation for reduced bodyweight. In one, a woman with SCZ developed AN in the context of a belief that her boyfriend would marry her when she lost enough weight. She exhibited behaviors of food restriction and self-induced vomiting. At the time, she also reported being told to lose weight by her doctors. Her medical decompensation was swift due to lithium toxicity induced by dehydration. However, at the time of this decompensation she weighed 120 lbs. She did not begin to receive treatment for her weight loss until her weight reached 82 lbs. Many rounds of nutritional rehabilitation and medications were tried until the patient was stabilized on fluoxetine and fluphenazine decanoate (Muños et. al., 1997). In another, a 13-year-old girl with early onset SCZ had an onset of AN binge/purge type closely after. Starting on olanzapine worsened the symptoms due to fear of weight gain on the antipsychotic, and her parents encouraged her to vomit when she complained of fullness. Psychoeducation and cognitive behavior therapy were employed as well as a change in antipsychotic medication (Lai and Tan, 2014). Finally, a man with SCZ was described as having obsessive rituals around food including putting vinegar on all foods to keep his weight in a specific range.

4. Discussion

A systematic review of the prevalence and correlates of AN in people with SCZ identified 17 empirical studies, 18 case reports, and 4 reviews that met our inclusion criteria. The limited evidence suggests that the prevalence of AN diagnosis and symptoms in people with a primary diagnosis of SCZ are higher than in the general population, a finding that is in keeping with evidence of shared genetic liability between these disorders (Watson et. al., 2019; Zhang, 2021; Zhang 2023). The majority of the cohort studies in our review found an elevated prevalence of co-occurring SCZ and AN, and the reviewed case reports found several common correlates between symptoms of psychosis and restrictive eating behaviors, the most common being positive symptoms. Overall, despite a strong emphasis on the impacts of SCZ and its treatment on binge eating, assessment of restrictive eating and AN is an important and unmet clinical need. Of note, the evidence appears more mixed for SCZ in AN than AN in SCZ, though only the Malaspina study examines specifically AN in SCZ so more evidence is needed in this area.

The treatment of the SCZ, in particular the use of atypical antipsychotics, could have unintended consequences in individuals prone to restrictive eating and AN. In two separate case reports, individuals were distressed by the potential for, or experience of, weight gain attributed to medication (Lai and Tan, 2014; Wenokur and Luby, 1997). It may be important to monitor individuals with a history of or predisposition for disordered eating more closely when starting on antipsychotic medications. Notably, three of the cases involved themes of stigmatized beliefs around weight, including a case in which the patient reported that her doctor recommended weight loss and another in which an adolescent’s parents encouraged purging to avoid weight gain after starting olanzapine. Additionally, determining whether AN in such cases is the result of delusional beliefs or weight stigma – both self-stigma and stigmatizing messaging – is important for characterizing the nature of disordered eating behaviors and risk for development of an eating disorder. Increasing psychoeducation around elevated prevalence of AN in SCZ for both patients and providers may help address stigma and enhance monitoring of restrictive eating behaviors earlier in the course of AN illness.

Treating symptoms of one comorbid illness may have effects on symptoms of the other. For instance, a case series found that in people with AN experiencing malnutrition, nutritional restoration was associated with emerging symptoms of psychosis (Hugo & Lacy, 1998) In another case, when a 14 year old girl received intravenous nutrition, her AN cognitions were replace by psychosis (Yamashita et. al., 1999) . Mount Joy and Edgar and Jones posit that delusions in SCZ are different that overvalued ideas in AN based on both insight and perception—meaning that both the perceptual nature of the beliefs and the level of insight diverge. Taken together, these studies suggest that there is a difference between pathological beliefs in SCZ and AN (Edgar and Jones, 2018; Mountjoy et. al., 2014). This is important in terms of treatment because if the psychotic experiences are rooted in AN or a side effect of severe malnutrition, antipsychotics might not be necessary long term. By contrast, in one case series, the author posits that restriction could be a “defense against psychosis” and that it is clinically challenging to disentangle whether these patients are experiencing AN with psychosis or SCZ with AN. One review examined this by positing that disembodiment could be viewed as a transdiagnostic symptom that unites AN and SCZ (Poletti, Pretti, & Raballo, 2022).

A limitation of this review is that the search terms did not capture eating disorders under the other specified feeding or eating disorder category. For example, atypical anorexia, is an eating disorder in which all criteria of AN are met except that, despite significant weight loss, the individual does not reach absolute threshold low weight (i.e., a low weight relative to population norms). Indeed, a common theme throughout the case reports reviewed here was that disordered eating was not addressed until patients had decompensated significantly in terms of weight. This may be particularly problematic for people taking antipsychotic medications, as they may be less likely to experience an absolute low weight due to medication effects. Indeed, one of the included case studies exemplifying this phenomenon, describing a woman who did not receive treatment for her AN despite significant medical problems because her weight at the time did not fall below threshold level for diagnosis (Muños et. al., 1997). The disordered eating persisted, and she went on to lose sufficient weight to meet criteria for AN. Interventions for AN are most effective when started as soon as possible after the onset of restrictive eating behaviors, so delays in care may lead to poor outcomes (Allen et al.).

A limitation of the literature is that the studies were mostly clinically-ascertained samples. As a result, results may not generalize beyond specific patient populations, and it is advisable not to draw strong conclusions. For instance, individuals with SCZ and AN may be more likely to be treated on a psychotic disorder unit than an eating disorder unit, which is a potential explanation for why the prevalence of AN in SCZ seems higher than SCZ in AN.

The psychological and biological mechanisms examined in case reports in this review suggest that there is a link between the symptoms of SCZ and the onset of AN. In addition, the majority of empirical evidence suggest that AN occurs in individuals with SCZ at a prevalence that warrants further investigation. Future research should examine subthreshold disordered eating behaviors, extending this to restrictive eating in addition to binge eating, in people with SCZ to capture a more diverse array of experiences. Additionally, understanding risks for AN and related illnesses occurring both organically and in the context of antipsychotic use or malnutrition will be clinically relevant for effective care. Large scale longitudinal studies of individuals with psychotic disorders should examine the emergence and recurrence of eating pathology, in addition to other co-occurring disorders, to more definitively identify and characterize comorbidities of psychotic disorders and eating disorders including SCZ and AN.