By Will Boggs MD
Disrupted effective connectivity among brain regions involved in attention and interoception may underlie some of the cognitive features of melancholia, according to results of functional MRI studies.
"Through an iterative process, our study first used prototypic symptom- and sign-based features to diagnose melancholic and non-melancholic patient groups," Matthew P. Hyett from University of New South Wales, Australia, told Reuters Health by email. "Our main study findings of brain disconnectivity in melancholia likely underpin such phenotypic features, hence providing clinicians with insight into the biological causes of this disorder."
Melancholia, formerly called endogenous depression, is distinguished from nonmelancholic depression by its loss of pleasure in virtually all activities and its lack of improvement in response to positive events. About a quarter of patients with major depression have melancholic features.
Although melancholia has long been thought to have a strong biological component, there has been limited evidence to support its specific neurobiological origins, Hyett and colleagues write in JAMA Psychiatry, online February 18.
The team used functional MRI to investigate the effective connectivity (a measure of causal interactions) among networks subserving attention, salience, executive function, and internally generated thought in 16 patients with melancholic depression, 16 patients with nonmelancholic depression, and 16 controls with no history of mood or psychotic illness.
The melancholic group had markedly diminished inward connectivity of the right frontoparietal (RFP) component, significantly diminished outgoing connectivity of the insula (INS) to other components, and somewhat fewer outgoing connections from the left frontoparietal (LFP) component, the researchers found.
Specific disruptions in connectivity included reduced connections from the insula component to the right frontoparietal component, and from the insula component to the executive control (EXC) component.
"The involvement of the EXC mode is consistent with disturbances in executive function in melancholia, such as biased decision making," the researchers explain. "Neuroanatomically, our EXC mode overlapped substantially with portions of the ventromedial prefrontal cortex, which has a variety of affective control functions, including those related to self-reference, affect, and visceromotor regulation. Hence, this mode likely contributes to a range of affective control functions in addition to classic cognitive control."
"Our insular component was chosen specifically to incorporate the more anterior regions implicated in interoceptive processes," they add. "We observed a diminished outgoing influence of this anterior insula mode in participants with melancholia compared with healthy controls, particularly on the executive mode, which includes key regions (e.g., ventromedial prefrontal cortex) subserving affective control mechanisms."
"Taken together with the diminished connectivity of the RFP mode, this finding provides support for our hypothesis that melancholia is associated with disruptions to key regions underpinning attention and internalized mood state regulation," the team concludes.
Hyett said the "findings contribute to more detailed understanding of the neurobiology of melancholia, and if consensus is gained in future studies may assist in the development of more targeted physical treatments."
"There has been a significant shift in our understanding of brain function, which is likely to have a vast impact on the way we understand the neurobiology of psychiatric conditions," Hyett added.
JAMA Psychiatry 2015.
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