Table 1.
Recent Literature on Antidepressant Effects on Hippocampal Volume Deficits
| Reference | Method | Comparison | Findings |
|---|---|---|---|
| Cross-sectional analyses | |||
| Geerlings et al., 2012 | MRI | ≥65 y; depressed, HC | • Smaller volume in depressed (defined by CES-D score or AD use) vs HC • Smaller volume in AD users vs no AD use (defined as HC) |
| Huang et al., 2013 | MRI | Treated depressed (AD), untreated depressed (no AD; 10-pt lower HAM-D17), HC | • Lower hippocampus, CA1-3, and DG volume in depressed vs HC and no AD vs AD • AD intermediate between no AD and HC for CA1-3 |
| Nugent et al., 2013 | MRI | Depressed, remitted, HC | • Smaller volume hippocampus and thalamus in depressed vs remitted and vs HC • Remitted and HC did not differ |
| Arnone et al., 2013* | MRI | Depressed, remitted, HC | • Volume reduced in depressed vs remitted and HC; no difference between remitted and HC |
| Zhao et al., 2014 | MRI, meta-analysis | Untreated depressed, HC | • Smaller volume for depressed vs HC • Smaller volume in subgroup with first episode depression vs HC • No association with number of episodes |
| Travis et al., 2015 | MRI | Depressed (most taking AD), HC | • Similar volume between groups, but differences in DG • Duration of depression was negatively correlated with volume • No association between volume and memory scores |
| Schmaal et al., 2016 | MRI, meta-analysis | Depressed (some taking AD), HC | • Smaller volume for depressed vs HC • No volume difference in patients with first episode depression vs HC; smaller volume in patients with recurrent episodes • No significant effect of AD |
| Longitudinal analyses | |||
| Schermuly et al., 2011 | MRI, 4+ mo AD treatment |
Depressed, HC | • No difference between depressed and HC • Volume increased in depressed during treatment; change in volume was associated with baseline function but not depression scores |
| Sheline et al., 2012 | MRI 12 wk sertraline |
≥60 y; depressed, HC Remitters, nonremitters |
• Smaller volume for depressed vs HC at baseline • Smaller volume predicted poorer MADRS score • Smaller volume in nonremitters vs remitters |
| Husarova et al., 2012 | MRS 7–11 wk escitalopram or venlafaxine (MADRS responders only) |
Depressed; baseline vs postbaseline | • Myoinositol/creatine and phosphocreatine ratio negatively correlated with MADRS score at baseline • Lac/creatine and phosphocreatine ratio, an indicator of damage or dysfunction, decreased after AD treatment |
| Arnone et al., 2013* | MRI 8 wk citalopram |
Depressed, HC | • Volume increase after treatment • No difference between medicated and unmedicated remitters • Significant negative correlation between duration of untreated depression and hippocampal volume |
| Furtado et al., 2013 | MRI 3 mo TMS (some taking AD) |
Responders vs nonresponders | • Reduction in volume in nonresponders vs responders • No correlation with HAM-D17 score |
| Tendolkar et al., 2013 | MRI ECT treatment (TRD; previous AD treatment) |
Depressed; baseline vs posttreatment | • Increased volume after ECT |
| Godlewska et al., 2014 | MRI 8 wk escitalopram |
Responders vs nonresponders | • No significant effects • Trend toward normalization of volume in responders |
| Taylor et al., 2014 | MRI 2-y AD treatment (mostly sertraline) |
≥60 y; depressed, HC | • No difference from baseline for HC or remitted • Volume decrease over time for nonremitters • Significantly less volume for nonremitters vs HC at follow up • Worsening or nonimproving MADRS associated with decreasing volume |
| Elbejjani et al., 2015 | MRI 4 yr AD treatment (nonrandomized) |
≥65 y; history of depression vs no history | • Baseline: smaller volume with greater symptoms in women • Faster volume loss in women with history of depression vs no history • Slower loss with AD vs no AD in men with history of depression |
| Phillips et al., 2015 | MRI 6–12 mo AD treatment |
TRD; depressed, HC Remitters, nonremitters |
• No difference between depressed and HC at baseline • Remitters increased in volume, nonremitters decreased |
| Postmortem studies | |||
| Boldrini et al., 2012 | IHC; neural progenitor cells capillaries |
Untreated depressed, treated depressed (SSRI or TCA), NDC | • More neural progenitor cells and capillary area in individuals treated with SSRIs vs untreated depressed and vs NDC • Capillary area, number of progenitor cells, and volume were correlated in treated depressed subjects |
| Boldrini et al., 2013 | IHC; granule neurons | Untreated depressed, treated depressed (SSRI or TCA), NDC | • More granule cells in some areas of the DG in individuals treated with SSRIs or TCAs; numbers were between untreated depressed and NDC • No difference in glia cell numbers |
| Duric et al., 2013 | Gene expression; cytoskeletal proteins |
Depressed, NDC | • Dysregulation of pre- and postsynaptic genes in depressed subjects vs NDC |
Abbreviations: AD, antidepressant; CES-D, Center for Epidemiologic Studies-Depression; DG, denate gyrus; ECT, electroconvulsive therapy; HAM-D17, 17-item Hamilton Rating Scale for Depression; HC, healthy control; IHC, immunohistochemistry; MADRS, Montgomery-Åsberg Depression Rating Scale; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NDC, nondepressed control; TCA, tricyclic antidepressant; TMS, transcranial magnetic stimulation; TRD, treatment-resistant depression; SSRI, selective serotonin reuptake inhibitor.
*Included both cross-sectional and longitudinal analyses.