Digital archive of theses discussed at the University of Pisa


Thesis etd-10182015-174041

Thesis type
Tesi di dottorato di ricerca
Thesis title
Neuroplasticity and neurodegeneration in patients suffering from mood disorders: putative blood biomarkers and cognitive functions.
Academic discipline
Course of study
tutor Prof.ssa Dell'Osso, Liliana
  • mood disorders
  • depression
  • bipolar disorder
  • bdnf
  • beta-amyloid
  • neurodegeneration
  • neuroplasticity
Graduation session start date
The aim of my PhD program has been to explore the potential role of Brain-Derived Neurotrophic Factor (BDNF) and beta-amyloid (Aβ) peptides as blood biomarkers respectively of neuroplasticity and neurodegeneration in mood disorders. My research on the topic during PhD years lead to three original papers that I co-authored and included in this dissertation.
There is increasing evidence that BDNF is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The first presented study, conducted on samples of bipolar patients suffering from depressive and mixed episodes, shows that plasma BDNF levels are lower in both groups of patients than in healthy controls. These results appear largely in line with data reported in Literature, suggesting a role of peripheral (serum/plasma) BDNF levels as a state marker of mood episodes. Comparable BDNF levels in manic, depressive and mixed states suggest a shared biological trait strengthening the hypothesis of a unitary model for mood disorders. In spite of the apparent lack of diagnostic specificity of plasma BDNF measure, it could be useful as a surrogate biomarker of antidepressant efficacy. Moreover, BDNF studies have opened novel insight in the pathophysiology of mood disorders offering intracellular targets for future development of drugs.
Increasing evidence suggests that changes of Aβ plasma levels represent a blood protein signature to predict development of neurodegeneration in different diseases. Oligomeric Aβ has shown a great neurotoxic action: the inhibition of long term potentiation and the functional antagonism to BDNF are putative mechanisms. Not only have been changes in Aβ plasma levels described in patients suffering from Alzheimer’s Disease and Mild Cognitive Impairment, but also in depressed patients. Moreover, such changes resulted to be associated with risk for cognitive decline in general population cohorts. Patients with mood disorders present a great risk for dementia and generally for cognitive decline.
The second study of this dissertation shows significantly lower plasma Aβ42 levels and higher Aβ40/Aβ42 ratio in bipolar depressed patients than in control subjects. Moreover, a significant negative correlation emerges between Aβ42 plasma levels and the duration of illness, while a positive correlation results between the Aβ40/Aβ42 ratio and the number of affective episodes.
The last study demonstrates that Aβ peptides levels in a sample of drug-resistant bipolar depressed patients do not change with electroconvulsive therapy (ECT) regardless of clinical response. Furthermore, Aβ40/Aβ42 ratio is negatively correlated to the improvement of depressive and cognitive symptoms with treatment and remitter patients show a significantly lower Aβ40/Aβ42 ratio before ECT than non-remitter ones.
Although further research is necessary to establish firm conclusions about the role of Aβ in the pathophysiology of mood disorders, all these data would suggest that changes in plasma levels of different Aβ peptides might represent a useful tool to identify groups of bipolar patients with severe course of illness, poor response to treatments and at risk for cognitive decline.