Symptomatic Overlap Between Pellagra And Schizophrenia

  • Swati SharmaMaster of Dental Science - Operative Dentistry, King George’s Medical College, Lucknow, India
  • Tabassum Bint Sahar Biochemistry at King’s College London

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Introduction

Within medicine, neuropsychiatry and nutrition have traditionally operated in two distinct spheres of research and clinical treatment. Despite this, there is compelling evidence that nutritional deficiencies may have a causative link to the development of disruptive psychological symptoms.1 Patients often rely upon online services to gain clarity on the precise reasons that underpin complex symptoms such as psychosis, confusion, and cognitive impairment. These symptomatic categories can be observed in individuals suffering from pellagra, a nutritional deficiency of vitamin B3 (niacin) and tryptophan as well as schizophrenia, a chronic mental health disorder.2

Although there is no causative association between the two conditions, the nature of the mental disturbances experienced by pellagra patients have been described as ‘schizoid’.3 Pellagra occurs in those suffering from a range of psychiatric illnesses, including schizophrenia.4 Understanding the symptomatic overlap between these two diseases can reveal the complex and lasting psychological consequences of inadequate nutrition. If you are curious as to how exactly the clinical presentation of these conditions signals the importance of keeping your diet varied and nutritious, keep reading.

Pellagra: nutritional deficiency and neurological symptoms

Pellagra, a nutritional deficiency disease, is caused by chronically low levels of the B-3 vitamin niacin (nicotinic acid). The essential amino acid tryptophan helps to synthesise nicotinic acid.5 Essential dietary sources that are rich in niacin include:

  • Beef (liver, kidney)
  • Fish (salmon, tuna, trout, mackerel)
  • Poultry (chicken, duck)
  • Dairy (milk, cheese, yoghurt) 
  • Whole grains (brown rice, quinoa, barley)
  • Seeds (sunflower, sesame) 

The pellagra patient populace typically consists of individuals who are malnourished due to circumstances out of their control. Impoverished communities that cannot sustain or access a nutritious diet and corn-dependent populations that rely on maize (which contains a non-absorbable form of niacin), are unfortunately unable to tailor their diet to increase niacin intake.6 The patients suffering from particular forms of cancer, malabsorption, and anorexia are also at risk of developing pellagra.7,8

Pellagra develops as a result of malnutrition, and the clinical presentation of the disease can chronically and differentially impact an individual's skin, digestion and nervous system. 

Dermatitis symptoms include:9 

  • Facial rashes
  • Discolouration 
  • Thickened or scaly skin 
  • Burning skin patches 

The neurological symptoms of pellagra include:

  • Cognitive impairment
  • Dementia
  • Tremors
  • Depression
  • Delirium 
  • Psychosis

The clinical presentation of pellagra is not universal and absolute. Depending on the degree of niacin deficiency and how long a patient has suffered undernourishment, there are varying degrees of psychiatric disturbance. Irritability, anxiety, and depression are symptoms of an earlier display of psychological change.3 Chronic forms of pellagra have led to impairments in memory, as well as delirium, confusion, and even a comatose state.8 Several multi-system changes occur in the human body due to pellagra that may be life-changing. In the most chronic and untreated forms, pellagra can result in death. 

Niacin and tryptophan supplementation, tailored dietary changes to include niacin-rich foods, continued monitoring and neurological symptom assessments are essential to tackle pellagra.6 As nutritional deficiency diseases fundamentally impair nervous system function, early therapeutic intervention is essential to prevent irreversible damage.

Schizophrenia: hallmark diagnostic criteria and psychological symptoms

As a neuropsychiatric disorder that chronically impacts thought, perception, behaviour, and emotional affect, schizophrenia severely impacts individual functioning. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), provides a detailed classification system with symptomatologic criteria that is necessary for diagnosis.10 Aside from the duration of disturbance, identifying possible confounding causes, and classifying the corresponding sub-type, the disorder is characterised by the following criteria:

  • Cognitive impairment and psychosis: delusions, hallucinations, or disorganised speech 
  • Catatonic or disorganised behavioural effect
  • Restricted ability to express emotion and low emotional lability

It is difficult to establish the precise causes of schizophrenia; a combination and complex interplay of genetic, environmental, and neurodevelopmental factors influence the development of schizophrenia.2 Of these combinatorial risk factors, having a parent or sibling with schizophrenia significantly increases the chances of developing the disorder.11 Further, prenatal factors including maternal malnutrition and infection have been associated with the development of schizophrenia. 

Treating schizophrenia, as is in the case of pellagra, is absolutely crucial and time sensitive. Schizophrenic individuals must be afforded with a precise, targeted, and individual therapeutic approach. This includes antipsychotic medication, cognitive behavioural therapy and psychosocial observation and intervention.10

The link between pellagra and schizophrenia: nutritional deficiency and psychosis

Historic associations between pellagra and schizophrenia are rooted in the physiological state of nutritional deficiency. Whilst pellagra does not cause schizophrenia, the neurological symptoms observed in both disorders are clinically significant, similar and enduring. Decreased niacin levels can result in aberrant cognitive change, as niacin is essential for the synthesis of neurotransmitters and the maintenance of neuronal integrity.12,13

Therefore, if left untreated, neurological damage manifests in impaired cognitive function and changes in patient behaviour.12 Disorientation, memory loss, confusion and hallucinations occur in pellagra patients.3,10 Schizophrenic patients also display these exact symptoms, which similarly lead to severe impairment of daily function and quality of life. However, schizophrenia is inherently a multi-factorial neuropsychiatric disease. It cannot be attributed to any single nutritional factor alone.

Studies attempting to examine a concrete link between the two conditions have suggested that maternal prenatal niacin deficiency due to malnourishment may limit foetal capacity to use niacin efficiently for neuronal processing.13 Although this is speculative, we must recognise that psychosis is a widespread and life-altering psychiatric disturbance that develops from a wide range of pathologies, and critically requires immediate treatment. The life-threatening nature of both conditions is due to different aetiologies – death in schizophrenic patients is often due to attempted suicide rather than from direct damage to the nervous system as is the case in pellagra patients.4,10

The core aspects of symptomatic overlap observed are:

  • Cognitive impairment leading to changes in the nature of thoughts, emotions, memory, and speech
  • Depressive and anxious behavioural effects with increasing severity if left untreated
  • Delirium and hallucinations as a result of psychosis
  • Nutritional deficiency may have a contributory role in the severity of psychotic symptoms observed in schizophrenia, but is the central causative factor in the development of pellagra

Dietary intervention and planning for clinical treatment

As failure to intervene in both disorders can result in a patient's death, it is essential to introduce precise, targeted treatments. Therapeutic intervention must be introduced soon after diagnosis.

In the case of schizophrenia, with a specific focus on nutrition and dietary management, a controlled diet has been hypothesised to contribute to the severity of patient symptoms. Vitamins B6, B12 and B3 are crucial for brain development and neuronal function. A chronic deficiency can worsen existing dysfunctional neural patterns.5,13 Neuropsychiatric dysfunction in this case, is a causal factor for the psychotic symptoms observed in schizophrenic patients. To avoid worsening psychiatric symptoms, the following dietary and psychosocial interventions can be taken:

  • Ensure a varied and balanced diet, rich in nutrients that are essential for neurological function, including B vitamins
  • Avoid poor dietary habits such as high sugar consumption, low fibre intake and overconsumption of ultra-processed foods. It is associated with changes to symptomatic severity
  • Observe the impact of antipsychotic medication on metabolic health
  • Ensure access to a nutritionist for educational and management purposes
  • Psychotherapy to manage behavioural changes that may impair the ability to sustain a balanced diet necessary for general health

Similarly, pellagra patients suffering from cognitive impairment and corresponding psychosis should seek the following dietary and psychosocial interventions:

  • Ensure a varied and balanced diet, with niacin-rich produce combined with niacin supplementation
  • Examine the precise causal factors, including pre-existing diseases and inaccessible nutritional resources, that have led to niacin-deficiency
  • Provide therapeutic intervention in combination with dietary change, in order to manage psychiatric symptoms that include depression, anxiety, and psychosis

To avoid an impact on cognition, a balanced diet rich in all B vitamins is required.12 Biomedical research efforts on the impact of human nutrition on psychiatric disturbance makes clear that nutritional deficiency can result in critical and aberrant changes in neurological function and integrity.13 Observing the overlapping psychological changes in both pellagra and schizophrenia demonstrates the far-reaching and devastating impact on cognitive impairment.

FAQs

Can nutritional supplements treat pellagra?

Pellagra can be treated by following lifestyle changes; limiting alcohol intake, eating a balanced diet, not smoking and regularly taking supplements.

What are the complications of pellagra?

Dementia and depression are the most common complications.

How long does it take to recover from pellagra?

With supplements, most people improve in a few days. Gastrointestinal symptoms are the first to heal, usually within the first week. Sores on the skin and mouth heal within two weeks. Advanced cases may take a long time to recover. Severe nerve damage and dementia may be irreversible.

Summary

For those with pellagra and schizophrenic patients with unidentified psychosis, nutritionists and physicians should strive to develop dietary literacy for B vitamins to inform and improve clinical and individual dietary planning. Chronic cognitive impairment is a characteristic symptom of niacin deficiency in pellagra patients. It signals the indispensable utility of vitamin B3 for the neural integrity and the mental health of individuals.

The clinical similarities between both disorders indicate that psychosis is a widely experienced and severely limiting feature of cognitive impairment. It is indisputable that dietary balance and nutrition are integral to body and brain function. Ultimately, there is no substitute for adequate nutrition. Thus, proper dietary intervention and planning is crucial for both schizophrenic and pellagra patients.

References

  1. Firth J, Gangwisch JE, Borsini A, Wootton RE, Mayer EA. Food and mood: how do diet and nutrition affect mental wellbeing? BMJ [Internet]. 2020 [cited 2024 Mar 19]; 369:m2382. Available from: https://doi.org/10.1136/bmj.m2382
  2. Redzic S, Hashmi MF, Gupta V. Niacin Deficiency. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Mar 19]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557728/
  3. Marques JG. Pellagra With Casal Necklace Causing Secondary Schizophrenia With Capgras Syndrome in a Homeless Man. Prim Care Companion CNS Disord [Internet]. 2022 [cited 2024 Mar 19]; 24(2):40040. Available from: https://doi.org/10.4088/PCC.21cr03014
  4. Hoffer A. Pellagra and Schizophrenia. Psychosomatics [Internet]. 1970 [cited 2024 Mar 19]; 11(5):522–5. Available from: https://www.sciencedirect.com/science/article/pii/S003331827071623X
  5. Dickerson JWT, Wiryanti* J. Pellagra and mental disturbance. Proceedings of the Nutrition Society [Internet]. 1978 [cited 2024 Mar 19]; 37(2):167–71. doi:10.1079/PNS19780021. Available from: https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/pellagra-and-mental-disturbance/BD5D4011A11BD34E63E6F7B3E11EC566.
  6. Carpenter KJ. The relationship of pellagra to corn and the low availability of niacin in cereals. Experientia Suppl. 1983; 44:197–222. Available from: https://pubmed.ncbi.nlm.nih.gov/6357846/ 
  7. Shah GM, Shah RG, Veillette H, Kirkland JB, Pasieka JL, Warner RRP. Biochemical assessment of niacin deficiency among carcinoid cancer patients. Am J Gastroenterol. 2005; 100(10):2307–14. Available from: https://pubmed.ncbi.nlm.nih.gov/16181385/ 
  8. Prousky JE. Pellagra may be a rare secondary complication of anorexia nervosa: a systematic review of the literature. Altern Med Rev. 2003; 8(2):180–5. Available from: https://pubmed.ncbi.nlm.nih.gov/12777163/ 
  9. Hegyi J, Schwartz RA, Hegyi V. Pellagra: Dermatitis, dementia, and diarrhea. Int J Dermatology [Internet]. 2004 [cited 2024 Mar 19]; 43(1):1–5. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4632.2004.01959.x
  10. Administration SA and MHS. Table 3.20, DSM-IV to DSM-5 Psychotic Disorders [Internet]. 2016 [cited 2024 Mar 19]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519704/table/ch3.t20/
  11. Le L, R K, B M, Mj G. Risk of schizophrenia in relatives of individuals affected by schizophrenia: A meta-analysis. Psychiatry Research [Internet]. 2020 [cited 2024 Mar 19]; 286:112852. Available from: https://www.sciencedirect.com/science/article/pii/S0165178119318608
  12. Ibrahim WW, Sayed RH, Kandil EA, Wadie W. Niacin mitigates blood–brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor. Progress in Neuro-Psychopharmacology and Biological Psychiatry [Internet]. 2022 [cited 2024 Mar 19]; 119:110583. Available from: https://www.sciencedirect.com/science/article/pii/S0278584622000756
  13. Young LM, Pipingas A, White DJ, Gauci S, Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and ‘At-Risk’ Individuals. Nutrients [Internet]. 2019 [cited 2024 Mar 19]; 11(9):2232. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770181/.

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Rithika Nalli

Master of Laws – LLM, University of Edinburgh

Rithika is a graduate in Medical Law & Ethics and Biological Sciences, interested in the intersection of neurology, biotechnology, and law. Her research experience includes bioinformatic analyses of gene regulation in schizophrenia, assessing UK regulations for neuromodulatory devices, and exploring the ethical implications of using implantable neurotechnology to treat neurological and neuropsychiatric disorders. She is interested in promoting legal and neuroethical discourse in this area to advance neuroscience and improve clinical outcomes.

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