Hippocampal volume as treatment predictor in antidepressant naïve patients with major depressive disorder

Zárate-Garza, Pablo Patricio; Ortega-Balderas, Jessica A.; Barquera, José Alfonso Ontiveros-Sánchez de la; Lugo-Guillen, Roberto Alejandro; Marfil-Rivera, Alejandro; Quiroga‐Garza, Alejandro; Guzmán-López, Santos; Elizondo‐Omaña, Rodrigo Enrique

doi:10.1016/j.jpsychires.2021.06.008

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…More recently, the hippocampal tail finding has been replicated with increasingly finer parcellations of the hippocampus in large samples( Maller, 2018 , Nogovitsyn et al, 2020 ). A recent naturalistic study found both left and right hippocampal volume predicted remission in a treatment-naïve cohort, which removes the confound of antidepressant history ( Zarate-Garza, 2021 ). Hippocampal volume has been examined with and without normalization by the whole-brain volume.…”

Section: Structural Predictorsmentioning

confidence: 99%

MRI predictors of pharmacotherapy response in major depressive disorder

Gerlach

Karim

Peciña

et al. 2022

NeuroImage: Clinical

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Section: Structural Predictorsmentioning

confidence: 99%

MRI predictors of pharmacotherapy response in major depressive disorder

Gerlach

Karim

Peciña

et al. 2022

NeuroImage: Clinical

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“…Research on conventional antidepressant treatments suggest that patients with larger pre-treatment hippocampal volume are more likely to have better treatment outcomes ( 15 , 16 ). There is also some initial evidence that pre-treatment hippocampal volumes correlate with ketamine antidepressant treatment response.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment

Zavaliangos-Petropulu,

McClintock,

Joshi

et al. 2023

Front. Psychiatry

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IntroductionSubanesthetic ketamine is a rapidly acting antidepressant that has also been found to improve neurocognitive performance in adult patients with treatment resistant depression (TRD). Provisional evidence suggests that ketamine may induce change in hippocampal volume and that larger pre-treatment volumes might be related to positive clinical outcomes. Here, we examine the effects of serial ketamine treatment on hippocampal subfield volumes and relationships between pre-treatment subfield volumes and changes in depressive symptoms and neurocognitive performance.MethodsPatients with TRD (N = 66; 31M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg) over 2 weeks. Structural MRI scans, the National Institutes of Health Toolbox (NIHT) Cognition Battery, and Hamilton Depression Rating Scale (HDRS) were collected at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks post-treatment. The same data was collected for 32 age and sex matched healthy controls (HC; 17M/15F; age = 35.03 ± 12.2 years) at one timepoint. Subfield (CA1/CA3/CA4/subiculum/molecular layer/GC-ML-DG) volumes corrected for whole hippocampal volume were compared across time, between treatment remitters/non-remitters, and patients and HCs using linear regression models. Relationships between pre-treatment subfield volumes and clinical and cognitive outcomes were also tested. All analyses included Bonferroni correction.ResultsPatients had smaller pre-treatment left CA4 (p = 0.004) and GC.ML.DG (p = 0.004) volumes compared to HC, but subfield volumes remained stable following ketamine treatment (all p > 0.05). Pre-treatment or change in hippocampal subfield volumes over time showed no variation by remission status nor correlated with depressive symptoms (p > 0.05). Pre-treatment left CA4 was negatively correlated with improved processing speed after single (p = 0.0003) and serial ketamine infusion (p = 0.005). Left GC.ML.DG also negatively correlated with improved processing speed after single infusion (p = 0.001). Right pre-treatment CA3 positively correlated with changes in list sorting working memory at follow-up (p = 0.0007).DiscussionThese results provide new evidence to suggest that hippocampal subfield volumes at baseline may present a biomarker for neurocognitive improvement following ketamine treatment in TRD. In contrast, pre-treatment subfield volumes and changes in subfield volumes showed negligible relationships with ketamine-related improvements in depressive symptoms.

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“…Various key molecules involved in the pathogenesis of major depression disorder or AD have been linked to the inhibition of neurogenesis ( Berger et al, 2020 ; Babcock et al, 2021 ; Walgrave et al, 2021 ). Brain imaging and postmortem studies of patients with either of these disorders indicate reduction in hippocampal volume perhaps due to reduced neurogenesis and loss of mature neurons ( Frimodt-Møller et al, 2019 ; Zarate-Garza et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Akebia saponin D protects hippocampal neurogenesis from microglia-mediated inflammation and ameliorates depressive-like behaviors and cognitive impairment in mice through the PI3K-Akt pathway

Liu

Xiao

et al. 2022

Front. Pharmacol.

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Given the ability of akebia saponin D (ASD) to protect various types of stem cells, in the present study, we hypothesized that ASD could promote the proliferation, differentiation, and survival of neural stem/precursor cells (NSPCs), even in a microglia-mediated inflammatory environment, thereby mitigating inflammation-related neuropsychopathology. We established a mouse model of chronic neuroinflammation by exposing animals to low-dose lipopolysaccharide (LPS, 0.25 mg/kg/d) for 14 days. The results showed that chronic exposure to LPS strikingly reduced hippocampal levels of PI3K and pAkt and neurogenesis in mice. In the presen of a microglia-mediated inflammatory niche, the PI3K-Akt signaling in cultured NSPCs was inhibited, promoting their apoptosis and differentiation into astrocytes, while decreasing neurogenesis. Conversely, ASD strongly increased the levels of PI3K and pAkt and stimulated NSPC proliferation, survival and neuronal differentiation in the microglia-mediated inflammatory niche in vitro and in vivo. ASD also restored the synaptic function of hippocampal neurons and ameliorated depressive- and anxiety-like behaviors and cognitive impairment in mice chronically exposed to LPS. The results from network pharmacology analysis showed that the PI3K-AKT pathway is one of the targets of ASD to against major depressive disorder (MDD), anxiety and Alzheimer’s disease (AD). And the results from molecular docking based on computer modeling showed that ASD is bound to the interaction interface of the PI3K and AKT. The PI3K-Akt inhibitor LY294002 blocked the therapeutic effects of ASD in vitro and in vivo. These results suggested that ASD protects NSPCs from the microglia-mediated inflammatory niche, promoting their proliferation, survival and neuronal differentiation, as well as ameliorating depressive- and anxiety-like behaviors and cognitive impairment by activating the PI3K-AKT pathway. Our work suggests the potential of ASD for treating Alzheimer’s disease, depression and other cognitive disorders involving impaired neurogenesis by microglia-mediated inflammation.

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Hippocampal volume as treatment predictor in antidepressant naïve patients with major depressive disorder

Cited by 11 publications

References 29 publications

MRI predictors of pharmacotherapy response in major depressive disorder

MRI predictors of pharmacotherapy response in major depressive disorder

Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment

Akebia saponin D protects hippocampal neurogenesis from microglia-mediated inflammation and ameliorates depressive-like behaviors and cognitive impairment in mice through the PI3K-Akt pathway

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