The 'discontinuity hypothesis' of depression in later life:clinical and research implications

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.</p

The 'discontinuity hypothesis' of depression in later life:clinical and research implications

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.</p

The 'discontinuity hypothesis' of depression in later life:clinical and research implications

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.</p

Prevalence and correlates of alexithymia in older persons with medically (un)explained physical symptoms

Objectives: Much is unknown about the combination of Medically Unexplained Symptoms (MUS) and alexithymia in later life, but it may culminate in a high disease burden for older patients. In the present study we assess the prevalence of alexithymia in older patients with either MUS or Medically Explained Symptoms (MES) and we explore physical, psychological and social correlates of alexithymia.  Methods and Design: A case control study was performed. We recruited older persons (>60 years) with MUS (N = 118) or MES (N = 154) from the general public, general practitioner clinics and hospitals. Alexithymia was measured by the 20-item Toronto Alexithymia Scale, correlates were measured by various questionnaires. Results: Prevalence and severity of alexithymia were higher among older persons with MUS compared to MES. Alexithymia prevalence in the MUS subgroup was 23.7%. We found no association between alexithymia and increasing age. Alexithymia was associated with depressive symptoms, especially in the MUS population. Conclusions: Alexithymia prevalence was lower than generally found in younger patients with somatoform disorder, but comparable to studies with similar diagnostic methods for MUS. Considering the high prevalence and presumed etiological impact of alexithymia in older patients with MUS, as well as its association with depression, this stresses the need to develop better understanding of the associations between alexithymia, MUS and depression in later life

Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression:Do We Have a Translational Perspective?

Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the "neurotrophin hypothesis of depression" involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD

Effectiveness of late-life depression interventions on functional limitations:A systematic review

Depression is one of the most prevalent mental disorders in older adults and leads to considerable decreases in health, well-being, and impaired functioning. Intervention studies have focused on the effects on symptomatic recovery, and most do not include functional recovery as an outcome. Reduction of functional limitations as a treatment goal in old-age psychiatry aligns with the values of older persons. The objective of this review was therefore to evaluate the effectiveness of late-life depression interventions on functional limitations. This systematic review identified 15 randomized controlled trials in which the effectiveness of different interventions on functional limitations was evaluated in patients with late-life depression. The interventions were categorized into four categories: psychological interventions, drug treatment, physical exercise, and collaborative care. Multicomponent and collaborative-care interventions appear to be the most promising for improvement of functional limitations, particularly in primary care and community-dwelling populations of older persons with symptoms of depression. There is, however, a lack of evidence regarding studies in specialized mental health care

Strengths and Weaknesses of the Vascular Apathy Hypothesis:A Narrative Review

The vascular apathy hypothesis states that cerebral small vessel disease (CSVD) can cause apathy, even when no other symptoms of CSVD are present. In order to examine this hypothesis, the objectives of this narrative review are to evaluate the evidence for a pathophysiological mechanism linking CSVD to apathy and to examine whether CSVD can be a sole cause of apathy. The nature of the CSVD-apathy relationship was evaluated using the Bradford Hill criteria as a method for research on the distinction between association and causation. Pathological, neuroimaging, and behavioral studies show that CSVD can cause lesions in the reward network, which causes an apathy syndrome. Studies in healthy older individuals, stroke patients and cognitively impaired persons consistently show an association between CSVD markers and apathy, although studies in older persons suffering from depression are inconclusive. A biological gradient is confirmed, as well as a temporal relationship, although the evidence for the latter is still weak. The specificity of this causal relationship is low given there often are other contributing factors in CSVD patients with apathy, particularly depression and cognitive deterioration. Differentiating between vascular apathy and other apathy syndromes on the basis of clinical features is not yet possible, while in-depth knowledge about differences in the prognosis and efficacy of treatment options for apathy caused by CSVD and other apathy syndromes is lacking. Since we cannot differentiate between etiologically different apathy syndromes as yet, it is premature to use the term vascular apathy which would suggest a distinct clinical apathy syndrome