Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder

Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. The primary aim of this pilot study was to investigate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) monotherapy, compared to sertraline monotherapy, for patients with acute MDD. This open-label, nonrandomized controlled trial examined a MBCT cohort (N=23) recruited to match the gender, age, and depression severity of a depressed control group (N=20) that completed 8 weeks of monotherapy with the antidepressant sertraline. The 17-item clinician-rated Hamilton Depression Severity Rating Scale (HAMD-17) was the primary outcome measure of depression to assess overall change after 8 weeks and rates of response and remission. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) was the secondary outcome measure to further assess depression severity. Both cohorts were demographically similar and showed significant improvement in depression ratings. No difference was found in the degree of change in HAMD-17 scores (t(34) = 1.42, p = .165) between groups. Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 (t (32) = 4.39, p < 0.0001), with the MCBT group showing greater mean improvement. This study was limited by the small sample size and non-randomized, non-blinded design. Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and a viable alternative to antidepressant medication. Greater changes in the self-rated QIDS-SR16 for the MBCT cohort raise the possibility that patients derive additional subjective benefit from enhanced self-efficacy skills

Psychosomatic and Biopsychosocial Medicine: Body-Mind Relationship, Its Roots, and Current Challenges

The basis of psychosomatic medicine is a fundamental philosophical debate between mind (a subjective phenomenon that is linked to a sense of consciousness) and body (which is empirically demonstrable). Starting from the Greek tradition to the Cartesian res cogitans-res extensa dichotomy, the chapter illustrates the role and importance of a biopsychosocial approach in all the spheres of medicine as a way to contrast the still evident modern medicine reductionism. The evidence coming from biological, psychological, and social science, merging in biopsychosocial (or psychosomatic) integrated view in medicine, is also discussed. Although the term psychosomatic can be misleading, since, as Alexander underlined in the first issue of the journal Psychosomatic Medicine in 1939, it may imply dichotomy between psyche and body (soma). If however we understand psychic phenomena as nothing but the subjective aspect of certain bodily (brain) processes, this dichotomy disappears, becoming medicine of the whole person, away from scientistic reductionism and toward the embrace of the complex in clinical practice