New insights into the genetic risk for schizophrenia, the role of inflammation in schizophrenia pathophysiology, the relationship between negative symptom domains and basic emotions, and cognitive endophenotypes for schizophrenia were presented in an oral presentation session at EPA 2022.
Risk associated with protein-truncating variants in genes implicated in schizophrenia
"The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium has identified protein-truncating variants (PTVs) in 10 genes associated with schizophrenia", said Professor David Curtis, London, UK.
Most carriers of protein-truncating variants in genes implicated in schizophrenia do not develop schizophrenia
He presented his study of exome-sequenced relatively healthy volunteers from the UK Biobank to determine whether these PTVs increase the risk of schizophrenia in the general population. He identified 251 UK Biobank participants who had PTVs in one of the 10 SCHEMA genes and analyzed the prevalence of psychiatric illness and educational and occupational function among these participants.
"The results showed that most carriers of protein-truncating variants in genes implicated in schizophrenia pathogenesis do not have subclinical manifestations of schizophrenia and do not develop schizophrenia",1 concluded Professor Curtis.
Support for an inflammatory role
Long-term antipsychotic treatment significantly reduced the osteopontin level and the neutrophil-to-lymphocyte ratio
Dr Marton Kovacs, Pecs, Hungary, presented a study of 22 patients with schizophrenia he had carried out with colleagues to evaluate the role of inflammation in the pathogenesis of schizophrenia.
"Elevated osteopontin (OPN) and interferon gamma (IFNɣ) serum levels and an increased neutrophil-to-lymphocyte ratio (NLR) were associated with more severe symptoms of schizophrenia", said Dr Kovacs.
In addition, serum OPN level (but not the IFNɣ level) and NLR were significantly decreased in patients on long-term antipsychotic therapy (8.8±5.9 years) compared to patients on short-term therapy (3.5±1.9 weeks).2
Relationship between negative symptom domains and basic emotions
A significant negative correlation between blunted affect and recognition of happiness was detected
Dr Marco Zierhut, Berlin, Germany presented a study he carried out with colleagues to explore the relationship between negative symptom domains and six basic emotions (anger, disgust, fear, happiness, sadness, surprise) in 66 patients with schizophrenia spectrum disorders (SSD).
"The results showed a significant negative correlation between blunted affect and recognition of happiness", said Dr Zierhut.3
Cognitive endophenotypes for schizophrenia
Executive function and attention appear to be cognitive endophenotypes for schizophrenia
Dr Rosa Ayesa-Arriola, Madrid, Spain, presented a family study of 133 first-episode psychosis (FEP) patients and 244 of their first-degree relatives she carried out with colleagues to explore cognitive function as an endophenotype.4
The results revealed that:
- FEP patients had the lowest function in all cognitive domains
- First degree relatives had an intermediate cognitive function between that of FEP patients and healthy controls
- Parents of patients with FEP who had a diagnosis of schizophrenia had impaired executive function and attention similar to that of their affected offspring4
"Executive function and attention could therefore be suitable cognitive endophenotypes for schizophrenia", concluded Dr Ayesa-Arriola.
EPA : European Psychiatric Association
SCHEMA : Schizophrenia Exome Sequencing Meta-analysis
PTV : protein-truncating variant
UK : United Kingdom
OPN : osteopontin
IFNɣ : interferon gamma
NLR : neutrophil-to-lymphocyte ratio
FEP : first-episode psychosis
BE-NOTPR-0258, approval date : 02.23
