2011
DOI: 10.1016/j.tins.2010.10.004
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Stuck in a rut: rethinking depression and its treatment

Abstract: The current definition of Major Depressive Disorder (MDD) emerged from efforts to create reliable diagnostic criteria for clinical and research use. However, despite decades of research, the neurobiology of MDD is largely unknown, and treatments are no more effective today than they were 50-70 years ago. We propose that the current conception of depression is misguiding basic and clinical research. Redefinition is necessary and may include a focus on a more narrowly defined set of core symptoms. However, we co… Show more

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Cited by 368 publications
(242 citation statements)
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“…It seems relevant therefore that activity in (37) and connectivity with (38) the mPFC is known to be elevated in depression and normalized after effective treatment (39). The mPFC was consistently deactivated by psilocybin (Fig.…”
Section: Discussionmentioning
confidence: 97%
See 1 more Smart Citation
“…It seems relevant therefore that activity in (37) and connectivity with (38) the mPFC is known to be elevated in depression and normalized after effective treatment (39). The mPFC was consistently deactivated by psilocybin (Fig.…”
Section: Discussionmentioning
confidence: 97%
“…3). Depression has been characterized as an "overstable" state, in which cognition is rigidly pessimistic (39). Trait pessimism has been linked to deficient 5-HT2A receptor stimulation (40,41), particularly in the mPFC (40), and mPFC hyperactivity has been linked to pathological brooding (42).…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, different syndromes and comorbidities may require different target combinations (97). To confirm the final potential central target, non-human primate models should be established according to the definition of refractory mental illness (98). Such a model should be selected based on the ability to imitate every psychotic symptom and pathological process entirely (97).…”
Section: Discussionmentioning
confidence: 99%
“…Accordingly, it has been proposed that sgACC hyperactivity could be a potential neurobiological marker for TRD (Greicius et al 2007;Guinjoan et al 2010;Holtzheimer and Mayberg 2011).…”
Section: Introductionmentioning
confidence: 99%