Table 2.

Summary of key findings supporting integrative neuroplasticity model

Plasticity marker	Relevance: Key empirical findings linking marker to depression (see main text for details and citations)	Integration: Findings directly linking marker to other levels of analysis	Causality: Does manipulating marker lead to generalized depression relief?
Molecular/cellular
↓Synapse number and function ↓Neurotrophic factors	Chronic stress induces synaptic deficits in mPFC and hippocampus, which lead to depressive-like behaviors in animal models ↓prefrontal synapses in patients post-mortem Decreased BDNF in depressed patients	--	Approach: Intravenous ketamine Evidence: Strong support12
Neural network
↓PFC-limbic circuit connectivity	Decreased PFC/limbic volumes, white matter integrity, intrinsic functional connectivity, and task-based connectivity in patients	↓PFC-limbic intrinsic83 and task-based42,43,105 connectivity linked to ↑negative attentional bias ↓intrinsic connectivity within limbic regions linked to ↑lassitude153	Approach: Neurofeedback Evidence: Preliminary support154,155 Approach: Neuromodulation of PFC Evidence: Moderate-to-strong support156
Cognitive Function
↓cognitive/executive control memory impairments (prospective memory deficits; overgeneral autobiographical memory)	Decreased executive functions Impaired and “over-general” memory recall	↓Self-reported cognitive control linked to ↑negative attentional bias157 ↓Self-reported cognitive control linked to ↑depression severity via ↑rumination158 ↑Overgeneral memory linked to ↑rumination and ↓executive function159	Approach: Cognitive control training Evidence: Preliminary support75 Approach: Autobiographical episodic memory training Evidence: Preliminary support160
Affective Information Processing
Attentional bias Interpretive bias Memory bias Biased self-associations Biased reward learning	Behavioral task performance supports the existence of each form of bias in depressed patients	Attentional bias: see above ↑negative biases in inhibitory control linked to ↑rumination7	Approach: Cognitive bias modification Evidence: Mixed/limited support108 (possibly related to difficulties in robustly modifying biases with current approaches)161 Approach: Evaluative conditioning of self-associations Evidence: Collateral/preliminary support162
Clinical/self-report
Inflexible thought patterns Inflexible behaviors	Repetitive negative thinking patterns (e.g. rumination, depressive schemas); constrained behaviors (e.g., lassitude) reported routinely by depressed patients	Lassitude and rumination: see above	Approach: Cognitive therapy Evidence: Strong support114 Approach: Behavioral activation Evidence: Strong support119