2026 ECNP Congress

PS02-2232

Tendency towards association between a single nucleotide polymorphism in the insulin–insulin-like growth factor 2 transcript and schizoaffective disorder

Kristina Melkersson — B. Persson · Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden

2026 ECNP Congress

Introduction

Schizophrenia is a psychotic disorder with high heritability. A variety of genes, each with small or moderate effect, have been suggested to be involved, and of all approximately 300 schizophrenia-associated genetic risk loci identified to date, it is the gene region encompassing the major histocompatibility complex on chromosome 6p22.1, playing an important role in the immune system, that is the most significant and consistent [1]. Evidence has also accumulated indicating that an autoimmune-mediated process may underlie the development of schizophrenia, and in two earlier studies, we found increased antibody reactivity against the insulin receptor-A and insulin-like growth factor 1 receptor and their ligands (insulin and insulin-like growth factor 1) in cerebrospinal fluid (CSF) and/ or serum from patients with schizophrenia or related psychosis, compared with from control subjects [2,3]. Hypothetically, the newly-identified insulin-insulin-like growth factor 2 (INS-IGF2) protein [4] may be a ligand to these receptors too, and in a recent study, a significantly higher antibody reactivity against a part of this protein was found in CSF and/ or serum in patients with schizophrenia or related psychosis in partial than full symptom remission [5]. However, the INS-IGF2 transcript that codes this protein has been little studied in schizophrenia and related psychosis.

Aims

The aim of this study was to identify single nucleotide polymorphisms (SNPs) in the part of the INS-IGF2 transcript that codes this present part of the protein [5] in patients with schizophrenia or schizoaffective disorder and control subjects.

Methods

The part of interest of the INS-IGF2 transcript was DNA-sequenced by the Sanger method in both directions in a study population, consisting of 94 patients with schizophrenia, 11 patients with schizoaffective disorder and 58 control subjects. In the statistical analyses, categorical data were summarized using frequency counts and percentages. Associations between genotype or allele frequencies and disease (schizophrenia or schizoaffective disorder versus controls) were analyzed with Chi-square test or Fisher’s exact test. A p-value of less than 0.05 was considered statistically significant.

Results

The DNA-sequenced part of the INS-IGF2 transcript was compared to the corresponding reference sequence, and totally two SNPs were identified. The two SNPs were found solely in patients, and not in control subjects. In comparison between patients with schizophrenia, patients with schizoaffective disorder and control subjects, tendencies towards overall significant differences in genotype- and allele frequencies were found for SNP no 1 (p=0.067 and p=0.067, respectively) that tended to be more common in patients with schizoaffective disorder. Single nucleotide polymorphism no 1 was present in 1 (9.1%) of 11 patients with schizoaffective disorder, and SNP no 2 was present in 1 (1.1%) of 94 patients with schizophrenia. The patient who carried SNP no 1 was a woman diagnosed with both schizoaffective disorder and polycystic ovary syndrome, and the patient who carried SNP no 2 was a woman diagnosed with schizophrenia (paranoid type with affective features).

Conclusions

The findings in this study point to that SNPs in the INS-IGF2 transcript may confer risk for psychosis, specifically for schizoaffective disorder.

References

  1. Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2022. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604, 502-508.
  2. Melkersson, K., Bensing, S., 2021. Increased antibody reactivity against insulin receptor-A and insulin like growth factor 1 receptor and their ligands in cerebrospinal fluid and serum of patient with schizophrenia or related psychosis. Neuroendocrinol. Lett. 42(5), 339-358.
  3. Melkersson, K., Bensing, S., 2023. Higher concentration in serum of insulin autoantibodies in patients with schizophrenia or related psychosis, compared to in control subjects. Neuroendocrinol. Lett. 44(6), 358-367.
  4. Cook, T.W., Wilstermann, A.M., Mitchell, J.T., Arnold, N.E., Rajasekaran, S., Bupp, C.P., et al., 2023. Understanding insulin in the age of precision medicine and big data: under-explored nature of genomics [review]. Biomolecules 13, 257.
  5. Melkersson, K., 2025. Antibody reactivity in cerebrospinal fluid and serum against the insulin-insulin-like growth factor 2 (INS-IGF2) protein is associated with psychotic symptomatology in patients with schizophrenia or related psychosis. Neuroendocrinol. Lett. 46(1), 1-14.