Friday, 12 September 2014

Insulin, growth hormone and risk of schizophrenia?

"Overall, the present findings suggest that metabolic and hormonal disturbances such as effects on insulin and growth hormone may represent a vulnerability factor to develop mental disorders". That was the conclusion reported by van Beveren and colleagues [1] (open-access) looking at "disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia".
"Years ago you served my father in the Clone Wars"

Drawing on data derived from participants taking part in the Genetic Risk and Outcome of Psychoses (GROUP) study [2] researchers looked at blood serum samples "to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls". Multiplex immunoassay was the analytical weapon of choice.

The results indicated that "10 proteins were present at significantly different levels between schizophrenia patients and controls" which can be seen here. The insulin synthesis pathway showed more than a passing connection to group differences as per the appearance of insulin and precursor molecules such as proinsulin and C-peptide (connecting peptide). Some of these pathway molecules were also reported to be altered in the sibling group(s) too. Growth hormone also featured as a potentially distinguishing marker, as did adiponectin among others.

The authors conclude (again) their findings for "the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia". Perhaps even more interesting is their view of the body of work [3] suggesting that "antipsychotic drugs are known to increase peripheral glucose levels" and how, in light of their findings, "these effects may be intrinsically related to the therapeutic mechanism of action by increasing the peripheral blood glucose levels and thereby increasing glucose availability in the brain".

As the authors point out, there is still quite a bit more to do in this area including examining larger samples sizes and importantly, looking at blood glucose levels as a measure of insulin resistance to further complement their findings. I note however that issues with insulin function being potentially related to mood and other psychiatric conditions are nothing new as per the various literature in this area. Anderson and colleagues [4] for example, talked about a diagnosis of diabetes doubling the odds of comorbid depression. Bearing in mind, the possible interfering effect of medication, Verma and colleagues [5] found that in drug-naive (unmedicated) patients with first-episode psychosis there was a significantly increased likelihood of diabetes to be present compared with age and sex-matched asymptomatic control participants. I don't doubt however, that any relationship is going to be complicated.

Finally, and bearing in mind the prime directive of this blog (no medical or clinical advice given or intended), there is the question of how this research might translate into therapeutic intervention. A final quote from the authors on this and the possibility of: "novel disease prevention approaches, which could involve nutrition modification, stress reduction and pharmaco-therapeutic interventions, including the application of well-tolerated drugs that combat insulin resistance". Alongside the dietary aspect (which is something very favourable to this blog for lots of reasons), I am wondering whether we could also learn something from times gone by [6]? Perhaps even the appliance of prophylactic psychiatry [7]?

Music to close and Andrea Bocelli sings Funiculì, Funiculà...


[1] van Beveren NJM. et al. Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia. Translational Psychiatry. 2014; 4: e430.

[2] Korver N. et al. Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort study focused on gene-environment interaction: objectives, sample characteristics, recruitment and assessment methods. Int J Methods Psychiatr Res. 2012 Sep;21(3):205-21.

[3] Wirshing DA. et al. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002 Oct;63(10):856-65.

[4] Anderson RJ. et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001 Jun;24(6):1069-78.

[5] Verma SK. et al. Metabolic risk factors in drug-naive patients with first-episode psychosis. J Clin Psychiatry. 2009 Jul;70(7):997-1000.

[6] Anderson K. et al. Salsalate, an old, inexpensive drug with potential new indications: a review of the evidence from 3 recent studies. Am Health Drug Benefits. 2014 Jun;7(4):231-5.

[7] Sawa A. & Seidman LJ. Is Prophylactic Psychiatry around the Corner? Combating Adolescent Oxidative Stress for Adult Psychosis and Schizophrenia. Neuron. 2014; 83: 991-993.

---------- van Beveren NJ, Schwarz E, Noll R, Guest PC, Meijer C, de Haan L, & Bahn S (2014). Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia. Translational psychiatry, 4 PMID: 25158005