Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 10  |  Issue : 1  |  Page : 71-74  

Is there an autoimmune basis for schizophrenia?


1 Department of Psychiatry, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India
2 Department of Medicine and Neurology, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India

Date of Web Publication9-Jan-2017

Correspondence Address:
Dr. (Brig.) Daniel Saldanha
Flat No. 1102, N Block, Grevillea, Magarpatta City, Pune - 411 013, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.197914

Rights and Permissions
  Abstract 

Etiology of schizophrenia still remains a mystery. Schizophrenia with coexistence of myasthenia gravis in the same patient raises the suspicion of autoimmune mechanisms involved in causation of schizophrenia.

Keywords: Autoimmunity, myasthenia gravis, schizophrenia


How to cite this article:
Tewari A, Saldanha D, Ostwal P, Chaudhari B. Is there an autoimmune basis for schizophrenia?. Med J DY Patil Univ 2017;10:71-4

How to cite this URL:
Tewari A, Saldanha D, Ostwal P, Chaudhari B. Is there an autoimmune basis for schizophrenia?. Med J DY Patil Univ [serial online] 2017 [cited 2024 Mar 29];10:71-4. Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2017/10/1/71/197914


  Introduction Top


Schizophrenia, a severe, disabling psychiatric disorder, is the fifth leading cause of years lost to disability for men and sixth leading cause for women.[1] Now classified as a schizophrenia spectrum and other psychotic disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,[2] it affects approximately 1% of the general population. Illness is characterized by personality deterioration, disturbances in affect, thought disorder, delusions, and hallucinations. Etiopathogenesis of schizophrenia being a mystery, various hypotheses proposed include neurodevelopmental, environmental, genetic, and infectious causes. Researchers in the 1980s had drawn attention toward autoimmunity as a possible mechanism for schizophrenia. Knight et al.[3] assembled evidence to show that schizophrenia is an autoimmune disease caused by autoantibodies that react with neuronal receptors influencing the limbic system. Chen et al.[4] did find occurrence of autoimmune disorders in schizophrenia having an association with 15 autoimmune disorders, which included celiac disease, Graves' disease, ankylosing spondylitis, psoriasis, and systemic lupus erythematosus among others. Myasthenia gravis is one such autoimmune disorder that has been reported in patients with schizophrenia disorder. We report a case of schizophrenia in which myasthenia gravis was also seen.


  Case Report Top


A 22-year-old unmarried, graduate male belonging to low socioeconomic status was admitted to a tertiary care hospital with complaints from his elder sister of being withdrawn and a tendency to wander around aimlessly, muttering to self, unprovoked aggression, neglecting self-care, and sleeping at odd hours of a month's duration. These abnormalities in his behavior had been seen soon after his mother's transient psychotic episode. There was no other psychiatric and medical history. Father, a case of alcohol dependence syndrome, had been treated in the past at the same tertiary care center.

General and systemic examination revealed bilateral fatigable ptosis [Figure 1], restriction of eye movements in all directions, and bifacial weakness of lower motor neuron type. There was no diplopia, muscles of mastication were normal, and palatal movements were good. The patient was of generalized thin built and there was no focal wasting of muscles. Power in shoulders was 3/5, elbow/wrist 4/5, hip 3/5, knee 4/5, and ankle 5/5. On tests of fatigability, there was reduction in arm abduction time - 20 s (normal: more than 3 min). Deep tendon reflexes were normal. Plantars were flexor.
Figure 1: The patient showing bilateral ptosis

Click here to view


On mental status examination, the patient was conscious and appeared oriented to surroundings, but it could not be checked formally as the patient was minimally communicative and passively cooperative and did not make eye contact; overall, psychomotor activity was reduced. Absorbed in self, he showed irritability at times. Silly smile was apparent. Speech was nonspontaneous, reduced in rate, tone, and volume. He was perplexed. Poverty of ideas was predominant. Hallucinatory behavior was observed; insight/judgment was impaired.

In view of abnormal neurological examination, we probed the relatives and it was revealed that he had easy fatigability and drooping of eyelids for the last few years, which was not investigated or treated.

Hemogram, renal function test, liver function test, random blood sugar, electrolytes, thyroid function test, and urine routine were within normal limits. Magnetic resonance imaging of the brain was normal. Neostigmine test showed positive response in terms of improvement in ptosis, arm abduction time, and the ability to get up from squatting [Table 1]. Repetitive nerve stimulation (RNS) at 3 Hz showed decremental response in bilateral orbicularis oculi and right abductor pollicis brevis muscles [Figure 2]. Contrast-enhanced computed tomography of the thorax showed thymic enlargement with patchy enhancement [Figure 3]. Anti-acetylcholine receptor (AChR) antibodies were negative.
Table 1: Neostigmine test

Click here to view
Figure 2: Repetitive nerve stimulation test shows slowing and decrement

Click here to view
Figure 3: Computed tomography of the thorax with contrast showing thymic enlargement with patchy enhancement

Click here to view


Based on the clinical features and investigations, a diagnosis of schizophrenia and myasthenia gravis was made. He was started on oral olanzapine 5 mg twice a day which was up-titrated to 15 mg per day at night. For myasthenia symptoms, neurological team had started him on oral prednisolone 5 mg per day, which was increased by 5 mg per day weekly to 20 mg per day. Oral pyridostigmine 60 mg three times a day was also given over 1 month in the hospital. The patient became more interactive and his self-care improved. Affect became more reactive and congruent to the thoughts, no perceptual abnormalities were reported at the end of 1 month, and patient gradually regained insight into his illness. His fatigability, ptosis, and motor power improved during this 1 month of inpatient stay. He was followed up on the outpatient department basis and maintained on olanzapine 5 mg, pyridostigmine 60 mg, and prednisolone 5 mg. The plan is to gradually taper off prednisolone and pyridostigmine if he continues to show improvement.


  Discussion Top


The clinical presentation of myasthenia gravis can be confused with symptoms of catatonia, especially in patients with prior undiagnosed myasthenia gravis as in our case. It can mimic extrapyramidal symptoms. The treatment with antipsychotic drugs can worsen myasthenic symptoms. Hence, there is need for evaluation of all cases to rule out possibility of a cooccurring neurological disorder for a proper management of the patient. Our patient's clinical features were a rare combination of psychosis and peripheral neuromuscular disease.

With more than 1 month of formal thought disorder and negative symptoms, the diagnosis of schizophrenia was established. Decremental response on RNS, positive neostigmine test, and fatigability were indicative of myasthenia gravis. In our patient, anti-AChR antibodies were not present. However, the absence of anti-AChR antibodies can be seen in a number of patients of myasthenia gravis. Thymic enlargement seen in our case is an indicator of autoimmune pathogenesis.

That autoimmunity plays an important role in the pathogenesis of myasthenia gravis is beyond doubt. In a recent review of literature on the autoimmune model of schizophrenia, Jones et al. highlighted the possibility of an autoimmune mechanism in a subset of schizophrenia patients based on associations with other autoimmune disorders and particularly major histocompatibility complex (MHC) haplotypes as well as increased serum levels of autoantibodies.[5] Eaton et al. examined a wide range of autoimmune diseases, revealing a higher co-prevalence with schizophrenia than assumed earlier. They concluded that patients with one or more autoimmune disorders had a 45% higher risk of schizophrenia, and their parents had a higher prevalence of 12 autoimmune diseases.[6] Musha et al. had proposed paraneoplastic autoimmune neuropsychiatric syndrome based on three cases of myasthenia gravis with thymoma presenting with psychotic symptoms in 1993.[7] Kim et al. too reported a chronic case of schizophrenia of over 20 years with myasthenia gravis; however, there was no thymoma.[8]

Increased autoantibodies and cytokine dysfunction, proinflammatory cytokine interleukin-6 (IL-6), have been seen to be higher in schizophrenia.[9] Most studies show an increase in IL-2 and soluble IL-2R in schizophrenia, indicating activation of T-cells in autoimmunity. Schizophrenia is also associated with an increase in the pro-inflammatory IL-1 and IL-6.In vitro production of interferon gamma from the lymphocytes may be dampened in schizophrenia patients. These findings are also consistent with an autoimmune disease. Studies do show dysregulation of inflammatory markers in cases of schizophrenia.[10]

Alterations in the production and circulation of systemic (not limited to nervous tissue) and organ-specific (limited to nervous tissue) antibodies have been demonstrated in the acute phase of schizophrenia.[11] Susceptibility to any illness due to various factors such as immune responses may involve multiple interacting genes. It has been observed that a gene family implicated in immunity and autoimmunity is also involved in schizophrenia. Jia et al. confirm genomic association of the MHC region with schizophrenia.[12]


  Conclusion Top


Association of autoimmune disorders points to an autoimmune cause in at least a subset of schizophrenia patients as outlined above. Evidence suggests a genetic component that predisposes the patients toward certain types of immune response and could be responsible for development of schizophrenia. However, more evidence is required to conclude an autoimmune basis for schizophrenia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
World Health Organization. The Global Burden of Disease. Geneva, Switzerland: World Health Organization; 2008.  Back to cited text no. 1
    
2.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013. p. 83-110.  Back to cited text no. 2
    
3.
Knight JG. Dopamine-receptor-stimulating autoantibodies: A possible cause of schizophrenia. Lancet 1982;2:1073-6.  Back to cited text no. 3
    
4.
Chen SJ, Chao YL, Chen CY, Chang CM, Wu EC, Wu CS, et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: Nationwide population-based study. Br J Psychiatry 2012;200:374-80.  Back to cited text no. 4
    
5.
Jones AL, Mowry BJ, Pender MP, Greer JM. Immune dysregulation and self-reactivity in schizophrenia: Do some cases of schizophrenia have an autoimmune basis? Immunol Cell Biol 2005;83:9-17.  Back to cited text no. 5
    
6.
Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, et al. Association of schizophrenia and autoimmune diseases: Linkage of Danish national registers. Am J Psychiatry 2006;163:521-8.  Back to cited text no. 6
    
7.
Musha M, Tanaka F, Ohuti M. Psychoses in three cases with myasthenia gravis and thymoma – Proposal of a paraneoplastic autoimmune neuropsychiatric syndrome. Tohoku J Exp Med 1993;169:335-44.  Back to cited text no. 7
    
8.
Kim H, Hong M, Bahn GH. Myasthenia gravis, schizophrenia, and colorectal cancer in a patient: Long-term follow-up with medication complexity. Psychiatry Investig 2013;10:300-2.  Back to cited text no. 8
    
9.
Ganguli R, Brar JS, Chengappa KN, Yang ZW, Nimgaonkar VL, Rabin BS. Autoimmunity in schizophrenia: A review of recent findings. Ann Med 1993;25:489-96.  Back to cited text no. 9
    
10.
Schwarz MJ, Chiang S, Müller N, Ackenheil M. T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun 2001;15:340-70.  Back to cited text no. 10
    
11.
Zandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, et al. Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 2011;258:686-8.  Back to cited text no. 11
    
12.
Jia P, Wang L, Fanous AH, Chen X, Kendler KS; International Schizophrenia Consortium, Zhao Z. A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia. J Med Genet 2012;49:96-103.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Table 1], [Figure 2], [Figure 3]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed3069    
    Printed111    
    Emailed0    
    PDF Downloaded197    
    Comments [Add]    

Recommend this journal