Major depression is one of the most prevalent and debilitating personal and public health conditions worldwide. Less appreciated is that depression's tremendous burdens are not shared equally among all who become depressed. Some will suffer recurrences over the rest of their lives, whereas half or more will never have a recurrence. Based on these two distinctive life course prototypes, we propose a subtype distinction for research on the origins and lifetime course of major depression. A pressing goal is to determine at the time of depression's first onset who will follow which clinical trajectory. The lack of recognition of this distinction has resulted in many obstacles, including conceptual biases, methodological oversights, and definitional dead ends. Current theories are reviewed and compared. The implications for contemporary diagnostic controversies, reevaluating research on treatment and prevention, and enhancing the predictive strength of traditionally weak indicators of recurrences and recurrent depression are discussed.
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http://dx.doi.org/10.1146/annurev-clinpsy-072220-021440 | DOI Listing |
PLoS Comput Biol
December 2024
Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Canada.
Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, and new pharmacology boosting this inhibition via positive allosteric modulators of α5-GABAA receptors (α5-PAM) offers a promising effective treatment. However, testing the effect of α5-PAM on human brain activity is limited, meriting the use of detailed simulations.
View Article and Find Full Text PDFEur Arch Psychiatry Clin Neurosci
December 2024
Department of Psychiatry, University of Muenster, Muenster, Germany.
Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.
View Article and Find Full Text PDFACS Chem Neurosci
December 2024
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Cracow 30-688, Poland.
The sodium-dependent membrane transporter SLC6A15 (BAT2) belongs to the SLC6 family, which comprises carriers of amino acids and monoamines. BAT2 is expressed in the central nervous system (CNS), including the glutaminergic and GABAergic system. SLC6A15 supplies neurons with neutral amino acids.
View Article and Find Full Text PDFJ Cardiovasc Dev Dis
November 2024
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ischemic stroke is a major cause of mortality and disability and has become a significant public health concern among women. Overall, women have more ischemic stroke events than men, in part due to their longer life span, and also suffer from more severe stroke-related disabilities compared to men. Women are also more likely than men to present with atypical non-focal neurological symptoms, potentially leading to delayed diagnosis and treatment.
View Article and Find Full Text PDFCurr Issues Mol Biol
November 2024
Systems Biology Unit, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, 23071 Jaén, Spain.
Neurological disorders such as Autism Spectrum Disorder (ASD), Schizophrenia (SCH), Bipolar Disorder (BD), and Major Depressive Disorder (MDD) affect millions of people worldwide, yet their molecular mechanisms remain poorly understood. This study describes the application of the Comparative Analysis of Shapley values (CASh) to transcriptomic data from nine datasets associated with these complex disorders, demonstrating its effectiveness in identifying differentially expressed genes (DEGs). CASh, which combines Game Theory with Bootstrap resampling, offers a robust alternative to traditional statistical methods by assessing the contribution of each gene in the broader context of the complete dataset.
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