Major depressive disorder: hypothesis, mechanism, prevention and treatment

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 9, 2024

Abstract Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, pathological mechanisms MDD underlying effects pharmacological treatments for are complex unclear, additional diagnostic therapeutic strategies still needed. The currently widely accepted theories pathogenesis include neurotransmitter receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis cytokine neuroplasticity hypothesis systemic influence but these cannot completely explain mechanism MDD. Even it hard to adopt only one reveal MDD, thus recent years, great progress has been made elucidating roles multiple organ interactions identifying novel approaches multitarget modulatory strategies, further revealing disease features Furthermore, some newly discovered potential targets studied antidepressants have attracted widespread attention, reagents even approved clinical treatment methods such as phototherapy acupuncture effective improvement symptoms. In this work, we comprehensively summarize latest research on diagnosis preventive medicines, well related trials.

Язык: Английский

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Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders

Nature Neuroscience, Год журнала: 2023, Номер 26(9), С. 1613 - 1629

Опубликована: Авг. 14, 2023

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the gray matter volume (GMV) differences in 1,294 cases diagnosed one six conditions (attention-deficit/hyperactivity disorder, autism spectrum bipolar depression, obsessive-compulsive disorder and schizophrenia) 1,465 matched controls. Normative models indicated person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting same area <7% diagnosis. However, these embedded within common functional circuits networks up to 56% cases. salience-ventral attention system was implicated transdiagnostically, other systems selectively involved schizophrenia attention-deficit/hyperactivity disorder. Phenotypic between assigned diagnosis may thus arise heterogeneous localization specific deviations, whereas phenotypic similarities be attributable dysfunction networks.

Язык: Английский

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Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation?

American Journal of Psychiatry, Год журнала: 2022, Номер 179(7), С. 458 - 469

Опубликована: Июль 1, 2022

Anhedonia—the loss of pleasure or lack reactivity to pleasurable stimuli—remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked poor disease course, worse response psychological, pharmacological, and neurostimulation treatments, increased suicide risk. Moreover, although some neural abnormalities normalize after successful treatment, several persist—for example, blunted activation the ventral striatum reward-related cues reduced functional connectivity involving striatum. Critically, these have also identified in unaffected, never-depressed children parents with disorder found prospectively predict first onset depression. Thus, may be promising targets for prevention. Despite appreciation clinical importance its underlying mechanisms, important gaps remain. this overview, author summarizes extant knowledge about pathophysiology anhedonia, which provide road map toward novel prevention strategies, then highlights priorities facilitate clinically meaningful breakthroughs. These include need 1) appropriately controlled trials, especially those embracing an experimental therapeutics approach probe target engagement; 2) preclinical models relevant stronger translational value; 3) scales that incorporate neuroscientific advances our understanding anhedonia. The concludes by highlighting future directions, emphasizing integrated, collaborative, cross-species, multilevel tackling anhedonic phenotypes.

Язык: Английский

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Canalization and plasticity in psychopathology

Neuropharmacology, Год журнала: 2022, Номер 226, С. 109398 - 109398

Опубликована: Дек. 27, 2022

This theoretical article revives a classical bridging construct, canalization, to describe new model of general factor psychopathology. To achieve this, we have distinguished between two types plasticity, an early one that call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, 'canalization', which is close Hebbian plasticity. These forms plasticity can be most easily by their relationship 'precision' inverse variance; TEMP relates increased variance decreased precision, whereas the opposite true canalization. also subsumes learning rate, (Ising) temperature entropy. Dictionary definitions 'plasticity' it as property being shaped molded; better match this. Importantly, propose 'pathological' phenotypes develop via mechanisms canalization defensive response adversity associated distress dysphoria. Our states entrenches in psychopathology, narrowing phenotypic state-space agent develops expertise pathology. We suggest - combined with gently guiding psychological support counter address questions whether when adaptive versus maladaptive, furnish our references basic human neuroscience, offer concrete experiments measures test its main hypotheses implications. part Special Issue on "National Institutes Health Psilocybin Research Speaker Series".

Язык: Английский

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Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge

Biological Psychiatry, Год журнала: 2022, Номер 93(12), С. 1089 - 1098

Опубликована: Окт. 29, 2022

Язык: Английский

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Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Май 9, 2023

Intravenous ketamine is posited to rapidly reverse depression by enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 single infusion of intravenous (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments pre-infusion baseline 24-h post-infusion. DTI mean diffusivity (DTI-MD), putative marker matter, was calculated for 7 interest (left right BA10, amygdala, hippocampus; ventral Anterior Cingulate Cortex) compared clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) Quick Inventory Depressive Symptoms-Self-Report (QIDS-SR). Individual differences DTI-MD change (greater decrease from post-infusion, indicative more enhancement) associated larger improvements scores across several regions. left BA10 these relationships driven primarily group (group * interaction effects: p = 0.016-0.082). associations generalized both arms (p 0.007). hippocampus, MADRS only, effects observed opposite direction, such that inversely arm specifically 0.032-0.06). The acute may be mediated, part, quantifiable DTI.

Язык: Английский

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Time-course of the tDCS antidepressant effect: An individual participant data meta-analysis

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2023, Номер 125, С. 110752 - 110752

Опубликована: Март 16, 2023

Язык: Английский

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Chronic psychosocial stress triggers microglial‐/macrophage‐induced inflammatory responses leading to neuronal dysfunction and depressive‐related behavior

Glia, Год журнала: 2023, Номер 72(1), С. 111 - 132

Опубликована: Сен. 7, 2023

Abstract Chronic environmental stress and traumatic social experiences induce maladaptive behavioral changes is a risk factor for major depressive disorder (MDD) various anxiety‐related psychiatric disorders. Clinical studies animal models of chronic have reported that symptom severity correlated with innate immune responses upregulation neuroinflammatory cytokine signaling in brain areas implicated mood regulation (mPFC; medial Prefrontal Cortex). Despite increasing evidence implicating impairments neuroplasticity synaptic deficits into the pathophysiology stress‐related mental disorders, how microglia may modulate neuronal homeostasis response to has not been defined. Here, using repeated defeat (RSDS) mouse model we demonstrate microglial‐induced inflammatory are regulating plasticity associated psychosocial stress. Specifically, show induces rapid activation proliferation as well macrophage infiltration mPFC, these processes spatially related activation. Moreover, report significant association microglial susceptibility or resilience In addition, find exposure exacerbates phagocytosis elements plasticity. Importantly, by utilizing two different CSF1R inhibitors (the penetrant PLX5622 non‐penetrant PLX73086) highlight crucial role (and secondarily macrophages) catalyzing pathological manifestations linked mPFC resulting usually depression.

Язык: Английский

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Annual Research Review: Neuroimmune network model of depression: a developmental perspective

Journal of Child Psychology and Psychiatry, Год журнала: 2024, Номер 65(4), С. 538 - 567

Опубликована: Март 1, 2024

Depression is a serious public health problem, and adolescence an ‘age of risk’ for the onset Major Depressive Disorder. Recently, we others have proposed neuroimmune network models that highlight bidirectional communication between brain immune system in both mental physical health, including depression. These draw on research indicating cellular actors (particularly monocytes) signaling molecules cytokines) orchestrate inflammation periphery can directly modulate structure function brain. In brain, inflammatory activity heightens sensitivity to threats cortico‐amygdala circuit, lowers rewards cortico‐striatal alters executive control emotion regulation prefrontal cortex. When dysregulated, particularly under conditions chronic stress, generate feelings dysphoria, distress, anhedonia. This initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) manage which further heighten inflammation. Over time, dysregulation these circuits response may compound each other form positive feedback loop, whereby one organ exacerbates other. We suggest this dynamic joint vulnerability depression, during adolescence. three goals present paper. First, extend developmental framework risk depression Second, examine how perspective help explain high rates comorbidity psychiatric disorders across development, multimorbidity stress‐related medical illnesses. Finally, consider identifying pathways facilitate ‘next generation’ behavioral biological interventions target treat, ideally prevent, youth adolescents.

Язык: Английский

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Do the therapeutic effects of psilocybin involve actions in the gut?

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(2), С. 107 - 117

Опубликована: Янв. 11, 2024

Язык: Английский

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