C- reactive protein in schizophrenia-spectrum disorders; relationship to cognitive functions and medications
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Background: Schizophrenia spectrum disorders are severe mental illnesses characterized by psychotic symptoms, cognitive dysfunction and functional decline. Cognitive impairments have been recognized as core features of schizophrenia, with great impact on functional outcome. Emerging evidence indicates involvement of immune system and inflammation in the pathophysiology of schizophrenia, and elevation of the inflammatory marker C-reactive protein (CRP) has been observed with association to pathogenesis and symptomatology including cognitive dysfunctions. Aims: To investigate the association between CRP level and cognitive performance in both acute phase of psychosis (paper 1) and during a 6 month follow-up (paper 2), and study the differences between antipsychotics with regards to effect on CRP levels during a one year follow-up of schizophrenia spectrum disorders patients in acute phase psychosis (paper 3). Methods: Participants from the Bergen psychosis project study were assessed with measurement of the CRP level and cognitive assessments at baseline and first followup visit at discharge/latest after 6 weeks (paper 1), in addition to cognitive assessments after 3 months and 6 months (paper 2). Patients from BestIntro study were assessed with measurement of CRP level at baseline, and after 1, 3, 6, 12, 26, 39 and 52 weeks (paper 3). Main results: Inverse relationship between baseline CRP level and overall cognitive performance, delayed memory and attention were found. During the 6 month followup global cognitive performance improved, and was associated with the initial CRP level reduction (paper1 and 2). Amisulpride, aripiprazole and olanzapine showed different effects on CRP levels, with a statistically significant increase in CRP levels during the first 1-3 weeks which lasted for 52 weeks for all groups. The aripiprazole group showed decrease in CRP level during the first week of treatment, and the change in CRP differed depending on whether or not the patient was antipsychotic-naïve (paper 3). Conclusions: Findings support an inflammatory component to the cognitive impairment in schizophrenia spectrum disorders, which is partly state dependent. The CRP level changes in the acute phase of psychosis may predict cognitive function in later phases. Amisulpride, aripiprazole and olanzapine showed different effects on the immune system in acute phase psychosis, which might be both phase related and dependent on whether or not there was prior use of antipsychotics. All three antipsychotics showed, however, an overall pro-inflammatory effect for the whole follow-up.
Består avPaper I: Erik Johnsen1, Farivar Fathian1, Rune A. Kroken, Vidar M. Steen, Hugo A. Jørgensen, Rolf Gjestad, Else-Marie Løberg: The serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis, BMC psychiatry. 2016:16-60. The article is available at: http://hdl.handle.net/1956/11957
Paper II: Farivar Fathian, Else-Marie Løberg, Rolf Gjestad, Vidar M. Steen, Rune A. Kroken, Hugo A. Jørgensen, Erik Johnsen: Associations between C-reactive protein levels and cognition during the first 6 months after acute psychosis, Acta Neuropsychiatrica. 2018:1-10. The article is available in the main thesis. The article is also available at: https://doi.org/10.1017/neu.2018.25
Paper III: Farivar Fathian, Rolf Gjestad, Rune A. Kroken, Else-Marie Løberg, Vidar M. Steen, Solveig Klæbo Reitan, W. Wolfgang Fleichhacker, Maria Rettenbacher, Tor K Larsen, Inge Joa, Lena Antonsen Stabell, Eirik Kjelby, Igne Sinkevicute, Renata Alisauskiene, Erik Johnsen.: Associations between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis. Manuscript. The article is not available in BORA.