Major Depressive Disorder (MDD) and Bipolar Disorder (BD) have a high prevalence
and detrimental socio-economic consequences for the patients and the community. Furthermore,
the depressive symptomatology of both disorders is essentially identical, thus rendering the clinical
differential diagnosis between the two significantly more difficult considering the concomitant lack
of objective biomarkers. Mood disorders are multifactorial disorders the pathophysiology of which
includes genetic, epigenetic, neurobiological, neuroimmunological, structural and functional brain
alterations, etc. Aberrant genetic variants as well as changed differential expression of microRNAs
(miRNAs) and long non-coding RNAs (lncRNAs) have been implicated in the pathophysiology of
MDD and BD. MiRNAs as well as lncRNAs have regulatory and modulating functions on protein--
coding gene expression thus influencing the remodeling of the architecture, neurotransmission, immunomodulation,
etc. in the Central Nervous System (CNS) which are essential in the development
of psychiatric disorders including MDD and BD.
Moreover, both shared and distinct structural, connectivity, task-related and metabolic features
have been observed via functional magnetic resonance imaging and magnetic resonance spectroscopy,
suggesting the possibility of a dimensional continuum between the two disorders instead of a
categorical differentiation. Aberrant connectivity within and between the Default Mode Network,
the Salience Network, Executive Network, etc. as well as dysfunctional emotion, cognitive and executive
processing have been associated with mood disorders.
Therefore, the aim of this review is to explore a more multidimensional framework in the scientific
research of mood disorders, including epigenetic and neuroimaging data in order to shape an outline
for their translational capacity in clinical practice.