Towards a multidimensional model of inflamed depression

The term depression is overused as an umbrella term for a variety of conditions, including depressed mood and various psychiatric disorders. According to psychiatric diagnostic criteria, depressive disorders impact nearly all aspects of human life and are a leading cause of disability worldwide. The widespread assumption that different types of depression lie on a continuum of severity has stimulated important research on subthreshold depression in later life. This view assumes that depressed mood is a precursor of a depressive disorder. The present narrative review argues why in later life depressed mood might either (i) lie on a continuum with depressive disorders among people vulnerable for a depressive disorder or (ii) be an ageing-related epiphenomenon of underlying physical illnesses in people who are resilient to depressive disorders (‘discontinuity hypothesis’). Three arguments are discussed. First, the course of depressed mood and depressive disorders differs across the life span. Second, screening instruments for depression have low predictive value for depressive disorders in later life. Third, a dose–response relationship has not been consistently found across different types of depression and detrimental health outcomes. Using the umbrella term depression may partly explain why pharmacological treatment is less effective with increasing age, and negative health-related outcomes might be overestimated. The discontinuity hypothesis may prevent pharmacological overtreatment of milder subtypes of depression and may stimulate comprehensive multidisciplinary assessment as well as the development of separate treatment algorithms for depressed mood and depressive disorders.

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Magnetic resonance imaging signatures of neuroinflammation in major depressive disorder with religious and spiritual problems

Kaszás,

Kelemen,

Kéri

2024

Preprint

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Religious and spiritual (R/S) struggles, such as questioning of faith, existential and ethical concerns, and interpersonal conflicts, are associated with depressive symptoms. Neuroinflammation is critical in major depressive disorder (MDD) and is linked to stress associated with R/S problems. This study aimed to assess whether the presence of DSM-5 R/S problems contributes to neuroinflammation. We recruited 93 MDD patients and 93 healthy controls with and without R/S problems. MRI-based restricted fraction (RF) values, an index of neuroinflammation, were measured in the hippocampus, amygdala, and neocortex. Depression and anxiety were assessed using the Hamilton Depression and Anxiety Rating Scales (HAM-D, HAM-A), while R/S problems were quantified using the Religious and Spiritual Struggles Scale (RSS-14). Results revealed elevated RF values in the amygdala and hippocampus of healthy individuals and MDD patients with R/S problems relative to those without R/S problems, with the highest values in MDD patients with R/S problems. Importantly, R/S problems and depressive symptoms were found to be independent predictors of RF values in the amygdala and hippocampus but not in the cortex. Elevated cortical RF values were associated with MDD. These intriguing findings indicate that R/S struggles are not secondary manifestations of depression but may independently contribute to neurobiological changes, engaging the audience in further research and discussion.

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Towards a multidimensional model of inflamed depression

Cited by 3 publications

References 100 publications

Connecting the dots from east to west

Connecting the dots from east to west

The ‘discontinuity hypothesis’ of depression in later life—clinical and research implications

Magnetic resonance imaging signatures of neuroinflammation in major depressive disorder with religious and spiritual problems

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