Limits...
Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.

van Beveren NJ, Schwarz E, Noll R, Guest PC, Meijer C, de Haan L, Bahn S - Transl Psychiatry (2014)

Bottom Line: Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation.In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117).Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands [3] Department 'Nieuwe Kennis', Delta Center for Mental Health Care, Rotterdam, The Netherlands.

ABSTRACT
Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.

Show MeSH

Related in: MedlinePlus

Boxplots showing altered levels of insulin and growth hormone in schizophrenia patients and siblings compared with controls. Serum concentrations of insulin (blue) and growth hormone (GH, yellow) were determined using multiplexed immunoassays for control, asymptomatic siblings (AS), symptomatic siblings (SS) and schizophrenia patients (SZ). The levels of insulin in controls were 4.3±5.0 μIU ml−1 and those for growth hormone were 3.7±6.3 ng ml−1. All values were log10 transformed to account for unequal distribution of the data. Bold horizontal bars reflect median protein levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150237&req=5

fig1: Boxplots showing altered levels of insulin and growth hormone in schizophrenia patients and siblings compared with controls. Serum concentrations of insulin (blue) and growth hormone (GH, yellow) were determined using multiplexed immunoassays for control, asymptomatic siblings (AS), symptomatic siblings (SS) and schizophrenia patients (SZ). The levels of insulin in controls were 4.3±5.0 μIU ml−1 and those for growth hormone were 3.7±6.3 ng ml−1. All values were log10 transformed to account for unequal distribution of the data. Bold horizontal bars reflect median protein levels.

Mentions: Of 10 altered proteins in schizophrenia patients, 5 of these showed significant differences in symptomatic siblings and 5 were also altered in asymptomatic siblings (Table 2). Four proteins (insulin, C-peptide, T-lymphocyte-secreted protein I 309 and growth hormone) were significantly altered in both symptomatic and asymptomatic siblings. Interestingly, insulin was consistently increased and growth hormone decreased in patients and both sibling groups compared with controls. Likewise, the insulin/growth hormone ratio was increased in patients (ratio=2.2; P<0.001), symptomatic siblings (ratio=1.9; P=0.0214) and asymptomatic siblings (ratio=1.4; P=0.0021) compared with controls (Figure 1). We next determined the proportion of subjects in each group that had high insulin/growth hormone ratios in schizophrenia patients and siblings compared with controls. Insulin/growth hormone values were dichotomized such that patients below the median (9.8 μIU ng−1) were partitioned into low group and those above the median were assigned to the high group. This showed that the highest proportion of subjects with high insulin/growth hormone values were found in the schizophrenia patient group (67%), followed by the symptomatic siblings (45%) and the asymptomatic siblings (43%) (Figure 2). The controls had a significantly lower proportion of high insulin/growth hormone values (30% P<0.001).


Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.

van Beveren NJ, Schwarz E, Noll R, Guest PC, Meijer C, de Haan L, Bahn S - Transl Psychiatry (2014)

Boxplots showing altered levels of insulin and growth hormone in schizophrenia patients and siblings compared with controls. Serum concentrations of insulin (blue) and growth hormone (GH, yellow) were determined using multiplexed immunoassays for control, asymptomatic siblings (AS), symptomatic siblings (SS) and schizophrenia patients (SZ). The levels of insulin in controls were 4.3±5.0 μIU ml−1 and those for growth hormone were 3.7±6.3 ng ml−1. All values were log10 transformed to account for unequal distribution of the data. Bold horizontal bars reflect median protein levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150237&req=5

fig1: Boxplots showing altered levels of insulin and growth hormone in schizophrenia patients and siblings compared with controls. Serum concentrations of insulin (blue) and growth hormone (GH, yellow) were determined using multiplexed immunoassays for control, asymptomatic siblings (AS), symptomatic siblings (SS) and schizophrenia patients (SZ). The levels of insulin in controls were 4.3±5.0 μIU ml−1 and those for growth hormone were 3.7±6.3 ng ml−1. All values were log10 transformed to account for unequal distribution of the data. Bold horizontal bars reflect median protein levels.
Mentions: Of 10 altered proteins in schizophrenia patients, 5 of these showed significant differences in symptomatic siblings and 5 were also altered in asymptomatic siblings (Table 2). Four proteins (insulin, C-peptide, T-lymphocyte-secreted protein I 309 and growth hormone) were significantly altered in both symptomatic and asymptomatic siblings. Interestingly, insulin was consistently increased and growth hormone decreased in patients and both sibling groups compared with controls. Likewise, the insulin/growth hormone ratio was increased in patients (ratio=2.2; P<0.001), symptomatic siblings (ratio=1.9; P=0.0214) and asymptomatic siblings (ratio=1.4; P=0.0021) compared with controls (Figure 1). We next determined the proportion of subjects in each group that had high insulin/growth hormone ratios in schizophrenia patients and siblings compared with controls. Insulin/growth hormone values were dichotomized such that patients below the median (9.8 μIU ng−1) were partitioned into low group and those above the median were assigned to the high group. This showed that the highest proportion of subjects with high insulin/growth hormone values were found in the schizophrenia patient group (67%), followed by the symptomatic siblings (45%) and the asymptomatic siblings (43%) (Figure 2). The controls had a significantly lower proportion of high insulin/growth hormone values (30% P<0.001).

Bottom Line: Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation.In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117).Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands [3] Department 'Nieuwe Kennis', Delta Center for Mental Health Care, Rotterdam, The Netherlands.

ABSTRACT
Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.

Show MeSH
Related in: MedlinePlus