The DOI matches its Crossref record; 75 of the 79 references it cites were found in a registry or an index; none of the 87 sources its claims cite is checked for support yet.
Cognitive impairment in major depressive disorder
Open accessAbstract
Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.
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In the paper
“Results from the International Mood Disorders Collaborative Project (IMDCP), a collaborative effort between the University of Toronto and Cleveland Clinic, indicated that cognitive function is a greater determinant of overall workplace function than measures of depression severity among working adults with MDD.”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
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In the paper
“Vice versa, functional impairments can also contribute to the persistence of cognitive symptoms in MDD. 9”
§ Cognitive impairment in major depressive disorder > Introduction
What the sources say
- Not checked yetcites [9] source
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In the paper
“Hitherto, only 2 antidepressants (ie, duloxetine and vortioxetine) have demonstrated direct, independent, and clinically relevant effects on cognitive dysfunction in MDD. 8”
§ Cognitive impairment in major depressive disorder > Introduction
What the sources say
- Not checked yetcites [8] source
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In the paper
“Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability.”
- Also stated in: § Introduction · boosted
“Many studies have shown that cognitive dysfunction, in particular, is a powerful predictor of occupational and social functional impairment in adults with MDD.[5][6][7]”
§ Cognitive impairment in major depressive disorder > Abstract
What the sources say
- Not checked yetcites [5][6][7]
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- Also stated in: § Introduction · boosted
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In the paper
“The trifecta of cognitive dysfunction, anhedonia, and depressed mood is thought to be a critical mediator of MDD-related functional disability.6,11”
§ Cognitive impairment in major depressive disorder > Introduction
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In the paper
“Indeed, individuals with inflammatory and metabolic comorbidities are at greater risks of mood disorders and cognitive dysfunction.13,14”
§ Cognitive impairment in major depressive disorder > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The persistence of cognitive deficits after remission of depressive symptoms has been shown to contribute to the failure in achieving full functional recovery in MDD. 5”
§ Cognitive impairment in major depressive disorder > Introduction
What the sources say
- Not checked yetcites [5] source
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In the paper
“Disparate neurobiological systems, including, but not limited to, arousal, mood, impulsivity, reward, anhedonia, energy, fatigue, and suicidality, all contribute to cognitive changes in MDD.16,17”
§ Cognitive impairment in major depressive disorder > Cognition: Glossary
What the sources say
- Not checked yetcites [16] source
- Not checked yetcites [17]
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Neurochemical changes (eg, catecholaminergic disturbances) have also been implicated as a mediator of cognitive dysfunction in MDD. 26”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [26] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“There is wide recognition of reciprocal relationships between mood, cognition, and metabolic disorders.38”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [38] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, anti-correlation, which refers to the selective reciprocal activation and deactivation of various brain regions, is critical for proper cognitive functioning.32”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [32] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, the findings of one study demonstrated that performance in verbal memory decreases as a function of episode frequency in MDD.29”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [29] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, most of the questionnaires that are used clinically to measure the severity of depressive symptoms (eg, Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale) tend to underemphasize cognitive symptoms.41”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
What the sources say
- Not checked yetcites [41] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, computer programs focused on sequencing mental arithmetic problems have been reported to improve full-scale intelligence quotient (IQ) in individuals with MDD.49”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [49] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, a recent review by Stanton and Reaburn 59 found that performing aerobic exercise 3-4 times a week for 9 weeks at moderate intensity is effective in alleviating depressive symptoms.59”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [59] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“For instance, the degree and severity of cognitive dysfunction has been shown to be mediated by the location of inflammation, neurotoxicity, and apoptosis.20”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [20] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Ventral affective networks, formed by the perigenual ACC, the amygdala, and the OFC, working in concert with the hippocampus, have also been shown to be important for a variety of cognitive processes such as establishing salience, mediating contextually appropriate responses, planning, working memory, and executive function.27”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [27] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The foregoing reduction in hippocampal volume may be a consequence of decreased neuronal and dendritic density, and/or reduced size of neuronal soma.28”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [28] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Likewise, a recent study showed lower depression relapse rates in individuals partaking in an aerobic exercise regimen compared to individuals treated with sertraline, a selectiveserotonin reuptake inhibitor (SSRI).50”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [50] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, evidence from a recent meta-analysis showed that reductions in cognitive function are predictive of poorer functional and metabolic outcomes.14”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
What the sources say
- Not checked yetcites [14] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, brain imaging studies in individuals with MDD have shown that rTMS may be a viable precognitive neuromodulatory strategy.57”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [57] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The well-established monoamine abnormalities in MDD likely contribute to impaired cellular signaling and neurocircuit deficits.19”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [19] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Specifically, MDD subjects exhibited greater activation of working memory networks relative to healthy controls.31”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [31] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Nodal structures such as the hippocampus, amygdala, and the anterior cingulate cortex (ACC) have demonstrated susceptibility to volumetric and functional changes as a consequence of greater illness severity, episode frequency, and duration.25”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [25] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“For example, evidence linking diabetes mellitus type 2 and insulin resistance with cognitive deficits in mood disorders is well-documented.39”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [39] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Studies have shown that brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) have procognitive effects in subpopulations with depression.55”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [55] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Manualized psychotherapy approaches (eg, cognitive behavioral therapy [CBT] and mindfulness therapies) are effective in the acute treatment of cognitive symptoms in MDD.52,53”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that individuals with MDD require greater neural effort to achieve the same level of cognitive performance as healthy controls.”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Dorsal cognitive networks, formed by the dorsal ACC working in concert with the hippocampus and the DLPFC, have been implicated in deficits of executive function.27”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [27] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In addition, cognitive impairment predicted overall psychosocial function in individuals with MDD. 6”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
What the sources say
- Not checked yetcites [6] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Acute physical activity (ie, single bout of exercise lasting between 10-30 minutes in duration) has been shown to have a positive impact on short-and long-term memory.60”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [60]
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“However, greater improvements in memory have also been observed with regular sustained exercise in individuals with mild cognitive impairments compared to individuals without cognitive impairments, suggesting that individuals with cognitive difficulties due to depressive disorders may be more sensitive to the procognitive effects of exercise.58,59,61”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, metabolic syndrome and obesity have been consistently shown to negatively impact cognitive functions.40”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [40] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Preliminary results suggest that adjunctive CRT may improve cognitive outcomes in individuals with MDD, when combined with pharmacotherapy.[45][46][47]”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [45][46][47]
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Cognition has been previously established as a principal mediator of health outcomes in MDD.42”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
What the sources say
- Not checked yetcites [42] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The structure, function, and chemical composition of fronto-temporal and fronto-subcortical circuitry have also been implicated in the emergence of cognitive symptoms in MDD.23,24”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Despite the foregoing typologies separating “hot” and “cold” cognition into distinct entities, a discrete separation between “hot” and “cold” cognition in neurobiological terms cannot be parsed.17”
§ Cognitive impairment in major depressive disorder > Cognition: Glossary
What the sources say
- Not checked yetcites [17]
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This objective is limited by the current clinical paradigm, which insufficiently addresses the deficits in cognitive function experienced by individuals with MDD, and the lack of mechanism-oriented drug development.”
§ Cognitive impairment in major depressive disorder > Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Elevated levels of circulating proinflammatory cytokines have been consistently reported in individuals with MDD.73”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [73] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Cognitive impairment has been observed in individuals with elevated inflammation.21”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [21] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, sertraline has been shown to improve psychomotor performance.63,64”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Duloxetine did not exhibit a statistically significant improvement when compared to placebo on composite measures of cognitive function in contradistinction to vortioxetine.67”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [67] source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, treatment strategies targeting brain insulin may prove efficacious in treating cognitive symptoms in MDD.”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Rests on an assumption: Intranasal insulin has cognitive-enhancing effects in MDD.
- Rests on an assumption: Intranasal insulin's cognitive benefits are greater in MDD patients who also have diabetes or insulin dysregulation.
- Rests on an assumption: In the brain, insulin blocks proapoptotic pathways and is important for neuroplasticity, neurogenesis, and neuronal growth and survival.
In the paper
“Ketamine, a dissociative anesthetic that antagonizes NMDA glutamatergic receptors, has been demonstrated to have rapid-onset antidepressant effects in individuals with treatment-resistant MDD.70”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [70] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This objective is limited by the current clinical paradigm, which insufficiently addresses the deficits in cognitive function experienced by individuals with MDD, and the lack of mechanism-oriented drug development.”
§ Cognitive impairment in major depressive disorder > Conclusion
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Specifically, as of May 2018, the FDA has updated the product monograph for vortioxetine based on data from the FOCUS and CONNECT trials to mention that vortioxetine is capable of improving performance on the Digit Symbol Substitution Test (DSST), indicating improvement in processing speed in individuals with MDD.67,68”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Available evidence indicates that baseline cognitive function may serve as a predictor of response to ketamine treatment.71”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [71] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cognitive deficit is a core domain of depressive psychopathology and a principal mediator of psychosocial and workplace functioning.”
§ Cognitive impairment in major depressive disorder > Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Notwithstanding the inconsistent evidence, lisdexamfetamine has been shown to specifically target and improve deficits in executive function in individuals with MDD, particularly among individuals with milder cognitive symptoms comorbid with executive function deficits.69”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [69] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In addition, vortioxetine appears to improve a broader range of cognitive functions (ie, executive function, learning, memory, processing speed, concentration) than duloxetine, which has only been shown to improve measures of learning and memory.66”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [66] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Treatment with TNF antagonists has been associated with lower depressive symptoms subscores in subpopulations with MDD comorbid with elevated peripheral inflammation 73 and in individuals with rheumatoid arthritis.75”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [73] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“In addition, vortioxetine appears to improve a broader range of cognitive functions (ie, executive function, learning, memory, processing speed, concentration) than duloxetine, which has only been shown to improve measures of learning and memory.66”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [66] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has been demonstrated to have procognitive effects compared to placebo.65”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [65] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The foregoing results validate previous findings suggesting neuroprotective and neurotrophic properties for liraglutide.”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Duloxetine did not exhibit a statistically significant improvement when compared to placebo on composite measures of cognitive function in contradistinction to vortioxetine.67”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [67] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Obtaining cognitive recovery in individuals with MDD is necessary to achieve optimal functional outcomes.”
§ Cognitive impairment in major depressive disorder > Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, bupropion and escitalopram have been reported to improve some aspects of verbal memory and delayed free recall.49,62”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Among the most consistently identified proinflammatory cytokine disturbances in MDD is tumor necrosis factor alpha (TNF-α).17,74”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [17]
- Not checked yetcites [74] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence also demonstrates efficacy of TNF antagonists in subgroups with treatment-resistant depression.76,77”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While both duloxetine and vortioxetine improved measures of depressive symptom severity, vortioxetine demonstrated a larger direct effect on RAVLT recall and acquisition scores compared to duloxetine.66”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [66] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Currently, vortioxetine is the only FDAapproved antidepressant agent that has demonstrated direct and independent procognitive effects in individuals with MDD.”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Moreover, it seems the antisuicidal effects of ketamine are mediated by improvements in executive function.71”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [71] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Insulin receptors are found throughout the brain, particularly in regions involved in cognitive and emotional processing.49”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [49] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Treatment with TNF antagonists has been associated with lower depressive symptoms subscores in subpopulations with MDD comorbid with elevated peripheral inflammation 73 and in individuals with rheumatoid arthritis.75”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [75] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 11
- Probably not a substantial claim. 6
- The quote only partly states this claim. 1
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD.”
§ Cognitive impairment in major depressive disorder > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Disturbances in concentration, executive function, decision-making, and learning and memory are part of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) items that determine whether an individual meets criteria for cognitive dysfunction in MDD.6”
§ Cognitive impairment in major depressive disorder > Cognition: Glossary
What the sources say
- Not checked yetcites [6] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, cognitive dysfunction in MDD has been proposed to be an endophenotype that worsens as a function of episode frequency.9,10”
§ Cognitive impairment in major depressive disorder > Introduction
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Individuals who are unemployed are more likely to exhibit decreases in cognitive performance and those who are employed will experience a greater loss of workplace productivity.7”
§ Cognitive impairment in major depressive disorder > Cognition: Implications of Function
What the sources say
- Not checked yetcites [7] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, CBT has shown to be effective in treating cognitive symptoms in ADHD, a disorder characterized by significant disturbances in executive function and attention.54”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [54] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For example, Siegle et al 48 reported that use of the Paced Auditory Serial Addition Test (ie, which requires patients to add sequentially presented digits) increased cognitive skills, decreased maladaptive thoughts (ie, rumination), and improved depressive symptom severity in individuals with MDD.48”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [48] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In one study, although performance on the n-Back test did not differ significantly between MDD subjects and healthy controls, differences were observed in the activation and deactivation of nodal substrates.31”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [31] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aerobic exercise improves cognition, has negligible side effects, and is scalable (ie, has the potential to be a population-wide health intervention).58”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [58] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Abnormalities in the connections between cortical and subcortical structures (ie, prefrontal cortical regions and the ACC) have been hypothesized to lead to poor functional outcomes in MDD.24,30”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mediators of aberrant neural circuitry, structure, and function are hypothesized to involve imbalances in hormonal regulation (ie, insulin resistance, glucocorticoid abnormalities), neurotrophin dysregulation (ie, brain-derived neurotrophic factor), immunoinflammatory activation, and oxidative stress.[34][35][36][37]”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [34][35][36][37]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Computerized working memory tasks have been shown to improve psychosocial and occupational functioning, as well as hippocampal and frontotemporal activation.50”
§ Cognitive impairment in major depressive disorder > Nonpharmacological interventions
What the sources say
- Not checked yetcites [50] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“One theory posits that abnormal activity in the medial prefrontal cortex may contribute to the requirement of increased neural effort in individuals with MDD. 31”
§ Cognitive impairment in major depressive disorder > Cognition: Neurobiology
What the sources say
- Not checked yetcites [31] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Infliximab is a promising TNF antagonist that binds to soluble and transmembrane domains of TNF-α, thus preventing the binding of TNF-α to its receptors.74,75”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Preliminary evidence indicates that liraglutide administered at a dose of 1.8 mg is able to improve depressive and cognitive measures in adults with a depressive mood disorder.72”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [72]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cognitive deficit is a core domain of depressive psychopathology and a principal mediator of psychosocial and workplace functioning.”
§ Cognitive impairment in major depressive disorder > Conclusion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“on vortioxetine also showed significant improvements in acquisition time and delayed recall.”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [66] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While both duloxetine and vortioxetine improved measures of depressive symptom severity, vortioxetine demonstrated a larger direct effect on RAVLT recall and acquisition scores compared to duloxetine.66”
§ Cognitive impairment in major depressive disorder > Pharmacological interventions
What the sources say
- Not checked yetcites [66] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Cognitive dysfunction is a core diagnostic criterion of major depressive disorder according to the Research Domain Criteria.
“Indeed, cognitive dysfunction is well established as a core diagnostic criterion of MDD according to the Research Domain Criteria (RDoC).”
The paper relies on this without support.
A significant subpopulation of individuals with major depressive disorder does not achieve functional remission after treatment with multiple FDA-approved pharmacological agents.
“A significant subpopulation of individuals with MDD does not achieve functional remission after treatment with multiple FDA-approved pharmacological agents.”
The paper relies on this without support.
Improvements in mood do not necessarily translate into improvements in function.
“It is important to note that improvements in mood do not necessarily translate into improvements in function.”
The paper relies on this without support.
Domain-specific cognitive deficits in learning and memory, executive function, processing speed, and attention and concentration are highly replicated findings in individuals with major depressive disorder presenting with a major depressive episode.
“Domain-specific cognitive deficits in learning and memory, executive function, processing speed, and attention and concentration are highly replicated findings in individuals with MDD presenting with a major depressive episode (MDE).”
The paper relies on this without support.
Individuals with major depressive disorder exhibit a bilateral reduction in hippocampal volume.
“It is recognized that individuals with MDD exhibit a bilateral reduction in hippocampal volume.”
The paper relies on this without support.
The reduction in hippocampal volume is proportional with the frequency of illness episodes.
“The reduction in hippocampal volume has also been shown to be proportional with the frequency of illness episodes.”
The paper relies on this without support.
Individuals with major depressive disorder exhibit hypoactivity of the prefrontal cortex, which is associated with increased activity of the anterior cingulate cortex.
“In addition, individuals with MDD exhibit hypoactivity of the prefrontal cortex, which is associated with increase in activity of the ACC.”
The paper relies on this without support.
Current antidepressant regimens do not primarily target psychosocial impairments and workplace disability in major depressive disorder.
“Despite the foregoing evidence, current antidepressant regimens do not primarily target psychosocial impairments and workplace disability in MDD.”
The paper relies on this without support.
Cognitive disturbances are more commonly observed in individuals with major depressive disorder compared to the general population.
“Cognitive disturbances are more commonly observed in individuals with MDD compared to the general population.”
The paper relies on this without support.
The specific efficacy of computerized measures of cognitive function in clinical populations remains elusive.
“Notwithstanding the foregoing evidence, the specific efficacy of computerized measures of cognitive function in clinical populations remains elusive.”
The paper relies on this without support.
Current psychotherapies primarily target hot cognitive deficits, and effective strategies targeting cold cognition still require further investigation.
“However, current psychotherapies primarily target “hot” cognitive deficits, and therefore effective strategies targeting “cold” cognition still require further investigation.”
The paper relies on this without support.
Brain stimulation therapies are associated with greater tolerability, reduced likelihood of cognitive impairment, and higher rates of remission in treatment-resistant individuals.
“For example, brain stimulation therapies have been associated with greater tolerability, reduced likelihood of cognitive impairment, and higher rates of remission in treatment-resistant individuals.”
The paper relies on this without support.
Available evidence indicates that improvements in measures of cognitive function with conventional antidepressants are associated with improvements in depressive symptom severity.
“Available evidence indicates that improvements in measures of cognitive function with the use of conventional antidepressants are associated with improvements in depressive symptom severity.”
The paper relies on this without support.
There is a paucity of FDA-approved pharmacological agents or interventions that are efficacious, tolerable, and specifically target cognitive dysfunction associated with major depressive disorder.
“There is currently a paucity of FDA-approved pharmacological agents and/or interventions that are efficacious, tolerable, and specifically target cognitive dysfunction associated with MDD.”
The paper relies on this without support.
Incretins may improve cognitive function.
“Preliminary data suggest that incretins may also improve cognitive function.”
The paper relies on this without support.
Intranasal insulin has cognitive-enhancing effects in MDD.
“For example, intranasal insulin has been shown to be procognitive in individuals with MDD.”
The paper relies on this without support.
Intranasal insulin's cognitive benefits are greater in MDD patients who also have diabetes or insulin dysregulation.
“In particular, the procognitive effects of intranasal insulin are stronger in individuals with a history of diabetes and insulin dysregulation comorbid with MDD.”
The authors state this as an assumption.
TNF-α antagonists are an effective add-on for cognitive symptoms in MDD.
“Treatment with TNF-α antagonists is postulated to be an efficacious adjunctive approach to target cognitive symptoms in individuals with MDD.”
The paper relies on this without support.
In the brain, insulin blocks proapoptotic pathways and is important for neuroplasticity, neurogenesis, and neuronal growth and survival.
“In the brain, insulin inhibits proapoptotic pathways and plays critical roles in neuroplasticity, neurogenesis, and neuronal growth and survival.”
The paper relies on this without support.
Psychostimulants are prescribed for depressive symptoms in MDD.
“Psychostimulants have also been used to treat depressive symptoms in individuals with MDD; however, available evidence is mixed.”
The paper relies on this without support.
Available evidence on psychostimulants for depressive symptoms in MDD is mixed.
“Psychostimulants have also been used to treat depressive symptoms in individuals with MDD; however, available evidence is mixed.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“BDNF can indeed cross the barrier in mice [110].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [110]
Experimental — accuracy not yet measured
Citations
Cites
Grand challenges in global mental health
Collins, P. Y., Patel, V., Joestl, S. S., March, D., Insel, T. R., Daar, A. S., Bordin, I. A., Costello, E. J., Durkin, M., Fairburn, C., et al. (2011) · Nature · doi:10.1038/475027a · Cited by 2,043
Smith, P. J., Blumenthal, J. A., Hoffman, B. M., Cooper, H., Strauman, T. A., Welsh-Bohmer, K., Browndyke, J. N., & Sherwood, A. (2010) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181d14633 · Cited by 1,714
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617
Heyn, P., Abreu, B. C., & Ottenbacher, K. J. (2004) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2004.03.019 · Cited by 1,223
Depression: A Global Public Health Concern
Marcus, M., Yasamy, M. T., van Ommeren, M., Chisholm, D., & Saxena, S. (2012) · PsycEXTRA Dataset · doi:10.1037/e517532013-004 · Cited by 997
Course of illness, hippocampal function, and hippocampal volume in major depression
MacQueen, G. M., Campbell, S., McEwen, B. S., Macdonald, K., Amano, S., Joffe, R. T., Nahmias, C., & Young, L. T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337481100 · Cited by 980
Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response
Pizzagalli, D. A. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.166 · Cited by 945
Siegle, G. J., Thompson, W., Carter, C. S., Steinhauer, S. R., & Thase, M. E. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.048 · Cited by 857
Hamilton, J. P., Furman, D. J., Chang, C., Thomason, M. E., Dennis, E., & Gotlib, I. H. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.003 · Cited by 823
McIntyre, R. S., Cha, D. S., Soczynska, J. K., Woldeyohannes, H. O., Gallaugher, L. A., Kudlow, P., Alsuwaidan, M., & Baskaran, A. (2013) · Depression and Anxiety · doi:10.1002/da.22063 · Cited by 765
Self-citation
Cited by
Sorted by citations
Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis
Wu, A., & Zhang, J. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02964-x · Cited by 354
“Moreover, the abilities of these antide-pressants to ameliorate cognitive deficits in patients suffering from MDD, especially memory impairments, have not been evaluated sufficiently during their development [34].”
BackgroundLiu, P., Gao, M., Liu, Z., Zhang, Y., Tu, H., Lei, L., Wu, P., Zhang, A., Yang, C., Li, G., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.800764 · Cited by 79
“MDD patients more commonly demonstrate cognitive disturbances than the general population (Pan et al., 2019).”
BackgroundKovtun, A. S., Averina, O. V., Angelova, I. Y., Yunes, R. А., Zorkina, Y., Morozova, A. Y., Pavlichenko, A. V., Syunyakov, T., Karpenko, O., Kostyuk, G. P., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10092162 · Cited by 67
Zhang, X., Zhang, R., Lv, L., Qi, X., Shi, J., & Xie, S. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.06.024 · Cited by 63
Koskinen, M.-K., van Mourik, Y., Smit, A. B., Riga, D., & Spijker, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-73173-2 · Cited by 64
Metadata
- Authors
- Pan, Z., Park, C., Brietzke, E., Zuckerman, H., Rong, C., Mansur, R. B., Fus, D., Subramaniapillai, M., Lee, Y., & McIntyre, R. S.
- Affiliations
- University Health Network (CA)
- Corresponding author
- McIntyre, Roger S.
- ORCID
- Venue
- CNS Spectrums
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-11-23
- Volume
- 24
- Issue
- 1
- Pages
- 22-29
- ISSN
- 1092-8529 (ISSN-L)
- 2165-6509
- OpenAlex
- W2901954088
- Semantic Scholar
- 3ed10b2aa1187ce71f325187e67ab657165d7191
- Cited by
- 320
- References
- 79
- Citations by year
- 2026: 50 · 2025: 65 · 2024: 80 · 2023: 52 · 2022: 37 · 2021: 26 · 2020: 5 · 2019: 4 · 2018: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Spectrums (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, cognitive impairment, learning and memory, executive function, processing speed, attention, antidepressants, neuroinflammation, neurobiological mechanisms, psychosocial functioning, quality of life, treatment goals
- MeSH terms
- Antidepressive Agents, Cognition, Cognition Disorders, Major Depressive Disorder, Depressive Disorder, Major, Humans, Nootropic Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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