Shridhar Sharma: Insulin coma treatment: Facts and controversies
Shridhar Sharma’s reply to Hector Warnes’ comments
I am thankful to Hector Warnes for his detailed comments on my essay Insulin Coma Treatment (ICT). You have personal experience of using ICT in schizophrenia in Lima. I agree with his observation that schizophrenia has a much higher insulin resistance than normal or neurotics. In his own words, “I was impressed with its immediate positive effects on severe acute schizophrenics”.
He has also reiterated the view that ICT was cumbersome and labor intensive. In ICT treatment, the role of nurses was very important. Recently, in a historical document, the role of nursing in the use of ICT for schizophrenia in Britain between 1936-1965 was reviewed (Adams, 2014). The report suggests that nurses in Britain were supportive of ICT. It also points out that “faced with a lack of rigorous research findings, clinicians preferred to rely on their clinical judgment. It may be emphasized that before 1950 there were hardly any controlled studies. Even the drug chlorpromazine was introduced in the market without any controlled studies based on the observation of a single patient. Similarly, our knowledge about brain receptors was also very limited.
I agree with Hector’s comments that I should have elaborated on the relationship between negative symptoms and plasma level of insulin-like growth factor I and the faulty modulation of dopaminergic neurotransmission. Recently, some researchers have suggested relationship between negative symptoms and plasma levels of insulin like growth factor I in first episode schizophrenics (Palomino A et al, 2013) and further explain that IGF-1 could have a role in the pathophysiology of negative symptoms. There is also evidence for a negative association between schizophrenia and polymorphism in the insulin receptor substrate 3 (IRS-3) gene suggesting that individuals carrying the A allele of this A/G SNP in the IRS-3 gene as well as the estimated haplotypes 5 or 3X including this A allele may offer protection against development of schizophrenia (Melkersson K and Persson B, 2012).
Some researchers have suggested altered levels of circulating insulin and other neuroendocrine hormone associated with the onset of schizophrenia. This could have important implication for future biomarker discovery efforts and personalized medicine strategies (Guest PC et al 2011). Several lines of evidence suggest that insulin receptor functioning may be abnormal in the brains of schizophrenics. Post mortem studies have also shown that persons with schizophrenia have less than half the number of cortical insulin receptors compared to healthy persons (Cara Vaggio F. et al, 2015). Association between diabetes and schizophrenia is well known (Suvisaari et al, 2016). People with schizophrenia have 2 to 5 fold higher risk of type 2 diabetes than the general population. Further, antipsychotic medications increase the risk of type 2 diabetes both directly by affecting insulin sensitivity and indirectly by causing weight gain.
References:
Adams J. The nursing role in the use of insulin coma therapy for schizophrenia in Britain,
1936-1965. J Adv Nurs. 2014; 70(9):2086-94.
Caravaggio F, Hahn M, Nakajima S, Gerretsen P, Remington G, Graff-Guerrero A.
Reduced insulin-receptor mediated modulation of striatal dopamine release by basal
insulin as a possible contributing factor to hyperdopaminergia in schizophrenia. Med
Hypotheses. 2015; 85 4): 391-6.
Guest PC, Schwarz E, Krishnamurthy D, Harris LW, Leweke FM, Rothermundt M, van Beveren NJ, Spain M, Barnes A, Steiner J, Rahmoune H, Bahn S. Altered levels of
circulating insulin and other neuroendocrine hormones associated with the onset
of schizophrenia. Psychoneuroendocrinology. 2011 Aug; 36(7): 1092-6.
Melkersson K, Persson B. Evidence for a negative association between schizophrenia and
a polymorphism in the insulin receptor substrate-3 (IRS-3) gene. Neuro Endocrinol +Lett. 2012; 33(3):321-30.
Palomino A, González-Pinto A, Martinez-Cengotitabengoa M, Ruiz de Azua S, Alberich S, Mosquera F, Matute C. Relationship between negative symptoms and plasma levels of insulin-like growth factor 1 in first-episode schizophrenia and bipolar disorder patients. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:29-33.
Suvisaari J, Keinanen J, Eskelinen S, Mantere O. Diabetes and Schizophrenia Curr Diab
Rep. 2016; 16(2): 16.
Vonberg FW, Bigdeli TB. Genetic Correlation between Schizophrenia and Epilepsy JAMA
Neurol. 2016; 73(1): 125-6.
Shridhar Sharma
October 27, 2016