At last, the relationship between Schizophrenia and Bipolar disorder begins to clear – Highlights from RCPsychIC 2019

Posted on:August 14, 2019
Last Updated: December 8, 2021
Time to read: 3 minutes

This summary is based on Prof Robin Murray’s talk at the RCPsych IC 2019.

1. Many patients diagnosed with treatment-resistant schizophrenia are found to have a mood disorder which requires treatment before patients begin to improve.

2. Genes that predispose to schizophrenia can be used to calculate the polygenic risk score (PRS) and estimate an individual’s liability to schizophrenia. [Allardyce J et al., 2018]

3. Polygenic risk scores (genetic risk score) is the cumulative risk derived from the combined contributions of several genes associated with a disease. The scores are derived from the variation of multiple genetic loci and their relative weights. PRS are not diagnostic and do not indicate that a person with a high score will develop the disease.

4. The polygenic risk score can also be applied to other conditions, and from a genetic point of view, there is an overlap between schizophrenia and bipolar disorder, [Allardyce et al., 2018] with around two-thirds of susceptibility genes in common.

5. One of the most striking differences between people with schizophrenia and bipolar disorder is cognitive difference.

Schizophrenia is characterized by significant deficits in premorbid intellectual function but the evidence regarding premorbid function in Bipolar Disorder is equivocal. After illness onset, patients with both disorders seem to suffer a further decline in cognitive function but the magnitude of the impairment remains greater in Schizophrenia than in Bipolar disorder. [Trotta A, et al., 2015]

6. The genes which determine this cognitive difference difference are simply those that identify lower IQ in the general population, and not genes associated with the illness.

This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. [Richards A et al., 2019]

7. GWAS reveals an overlap between schizophrenia (lower IQ genes), bipolar disorder (higher IQ genes), and intelligence. Genome wide association studies scan the genome for SNP’s (Single nucleotide polymorphisms) that occur more frequently in people with disease linking them to that disease or trait.

There is evidence for an early-childhood, persistent, pan-developmental impairment that is specifically associated with schizophreniform disorder and that predicts psychotic symptoms in childhood and adulthood. [Cannon M et al., 2002]

8. The mechanism underlying positive psychotic symptoms is an excess of striatal dopamine and several risk factors for psychosis impact on striatal dopamine. [Jauhar et al., 2019]

Risk factors such as cannabis use and childhood adversity are associated with striatal dopamine synthesis, and striatal dopamine dysregulation is recognised as the final common pathway underlying most psychoses. Learn more about the dopamine hypothesis of schizophrenia.

A recent study examined the role of dopamine synthesis capacity in bipolar psychsois comparing it to schziophrenia and if there is a link of excess dopamine sysnthesis capacity to positive psychotic symptoms irrespective of symptoms.  According to the authors:

Dopamine synthesis capacity is elevated in psychotic bipolar affective disorder to a similar degree to schizophrenia, and is related to severity of psychotic (positive) symptoms, extend previous findings that dopamine synthesis capacity is elevated in schizophrenia and psychosis associated with temporal lobe epilepsy, and increases with the onset of psychosis, to suggest that presynaptic dopamine dysfunction is associated with psychosis across diagnostic categories.

This provides a potential neurobiological explanation for why antipsychotic drugs, which are all dopamine 2/3 receptor blockers, are effective in bipolar psychosis as well as schizophrenia, and identifies the regulation of dopamine synthesis as a potential target for novel treatments for bipolar psychosis as well as schizophrenia. [Jauhar et al., 2017]

9. Shared polygenes with psychotic bipolar disorder influence liability to schizophrenia, and predispose to the development of dopamine dysregulation following environmental stressors.