Depression, negative symptoms and neuro-inflammation in schizophrenia

Krynicki, Carl Ryszard ORCID: 0000-0003-0943-5142 (2019). Depression, negative symptoms and neuro-inflammation in schizophrenia. University of Birmingham. Ph.D.

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Symptoms of depression such as low mood and apathy are common in schizophrenia. However, these overlap with negative symptoms such as apathy, poverty of speech and social avoidance and it remains very unclear the extent to which they share underlying pathogenic mechanisms and the degree to which distinct mechanisms converge to produce similar symptoms. Two pathogenic profiles have been proposed for negative symptoms; social amotivation and diminished emotional expressiveness. Recent evidence suggests a pro-inflammatory predisposition to both depression and negative symptoms of schizophrenia. The studies presented in this thesis aim to i) explore the relationship between depression and negative symptoms, ii) investigate whether they are driven by a common pro-inflammatory process, and iii) determine whether this may be a viable target for anti-inflammatory treatments. The analyses are based on data from a placebo-controlled clinical trial of minocycline (an anti-inflammatory antibiotic) to treat negative symptoms and reduce inflammatory markers.

Both in cross-section, and longitudinally over the course of the 12 months, depressive symptoms were associated with the avolition-apathy. Expressive deficits appeared specific to negative symptoms. The expressive deficit domain rather than depression-related avolition-apathy was associated with an immune abnormality throughout the 12-month clinical trial; namely increased TNF-α. Finally, the prescription of minocycline does not lead to a reduction in depressive and negative symptomology, nor inflammatory marker status.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: None/not applicable
Subjects: R Medicine > R Medicine (General)


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