The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

Table 1

Selected publications showing the effect of stress/depression or antidepressant treatment on neurogenesis and the functional importance of neurogenesis in antidepressant efficacy.

(a) Animal models of depression

Reference	Species	Sex	Model	Antidepressant	Method of ablation	Summary of findings
Snyder et al. 2011 [96]	Mouse	M	Restraint	—	X-ray; transgenic	Neurogenesis-dependent regulation of HPA response to stress and behavioural measures (NSF, FST, and SC)
David et al. 2009 [64]	Mouse	M and F	Chronic corticosterone administration	Fluoxetine	X-ray	Neurogenesis-dependent (NSF) and -independent (OFT, FST) aspects of antidepressant efficacy
Bessa et al. 2009 [65]	Rat	M	Chronic mild stress	Imipramine; fluoxetine	MAM	Neurogenesis-dependent (NSF) and -independent (SC, FST) aspects of antidepressant efficacy. Significant alterations in neural plasticity associated with antidepressant efficacy
Surget et al. 2008 [92]	Mouse	M	Chronic unpredictable stress	Imipramine; fluoxetine		Neurogenesis-dependent (NSF, CS, ST) and -independent (A) aspects of antidepressant efficacy
Holick et al. 2008 [93]	Mouse	M	—	Fluoxetine	X-ray	Neurogenesis-independent effects of antidepressant efficacy
Airan et al. 2007 [94]	Rat	F	Chronic mild stress	Imipramine; fluoxetine	X-ray	Neurogenesis-dependent (NSF) and -independent (OFT) aspects of antidepressant efficacy
Alonso et al. 2004 [85]	Mouse	M	Chronic mild stress	Fluoxetine	—	Decreased cell proliferation in the DG, while chronic fluoxetine blocked this effect
Santarelli et al. 2003 [21]	Mouse	M	—	Imipramine; fluoxetine	X-ray	Neurogenesis-dependent (NSF) antidepressant efficacy
Czéh et al. 2002 [78]	Rat	M	Social subordination	—	—	Decreased cell proliferation and survival in the DG
Malberg et al. 2000 [9]	Rat	M	—	Fluoxetine; reboxetine; tranylcypromine; ECS	—	Chronic, but not acute, treatment with monoaminergic antidepressant and ECS increased cell proliferation in the DG

(b) Human studies of depression

Reference	Subjects	Sex	Population assessed	Antidepressant	Effect on neurogenesis
Cobb et al. 2013 [74]	Humans	M and F	Depressed patients postmortem	—	No significant difference in number of granule cells between depressed subjects and controls; decreased hippocampal volume correlating with duration of disease
Boldrini et al. 2013 [75]	Humans	M and F	Depressed patients postmortem	SSRIs; TCAs	Depression is associated with a decreased number of granule neurons, correlated with reduced DG volume. SSRI and TCA treatment increase granule neuron number and DG volume
Boldrini et al. 2012 [22]	Humans	M and F	Depressed patients postmortem	SSRIs; TCAs	Both antidepressant classes increase cell proliferation over untreated depressed patients and controls; NPCs associated with angiogenesis
Boldrini et al. 2009 [23]	Humans	M and F	Depressed patients postmortem	SSRIs; TCAs	Both antidepressant classes increase cell proliferation over untreated depressed patients and controls
Stockmeier et al. 2004 [76]	Humans	M and F	Depressed patients postmortem	—	Increased density of granule cells in the DG of depressed subjects compared to controls

NSF: novelty suppressed feeding; FST: forced swim test; SC: sucrose consumption; OFT: open field test; CS: coat state; ST: splash test; A: actimeter; MAM: methylazoxymethanol acetate (cytostatic agent).