Major Depressive Disorder (MDD): Pathogenesis and clinical findings
Self blaming tendency
Major stressor(s)
↑ Emotional reactivity Monoamine deficiency
Regional brain area alterations
↓ Behavioral activation
(engagement in meaningful activities to improve mood)
Hunger interoception (perception & awareness of hunger) changes
Attributes the occurrence of negative events to internal/personal factors
Expectation that future events are uncontrollable & internally caused
Feelings of worthlessness or excessive guilt
Recurrent thoughts of death or suicide
Insomnia (melancholic MDD)
Dysregulation of negative feedback control on the hypothalamus–pituitary– adrenal (HPA) axis
↓ Serotonin & norepinephrine signaling
↑ HPA axis sensitivity
Heightened responses to stressors
Major Depressive
Disorder
≥5 symptoms/complications during the same 2-week period; at least 1 of **symptoms; causing clinically significant distress or impairment in social, occupational, or other important areas of functioning
↑ Amygdala activity Changes to neuronal activity
Altered prefrontal cortex & limbic functioning
Depressed mood**
Mechanism unknown; can
precede MDD or be a symptom
Psychomotor agitation (restlessness)
↓ Dopaminergic transmission in ventral striatum
Overactivation of the insula (brain region involved in integrating activity in reward & interoception circuitry)
Under activation of the insula
Mechanism unknown
↓ Activation of mesolimbic system (reward system)
↓ Motivation & anticipation for rewards
↑ Activation of mesolimbic system
Psychomotor
retardation (slowing) Poor concentration
↑ Motivation & anticipation for rewards
Anhedonia (loss of interest/pleasure)**
Anergia (lack of energy)
↑ Eating (particularly high- sugar foods)
Hypersomnia (atypical MDD)
↓ or ↑ Appetite &/or weight
Authors: Keira Britto Sara Cho JoAnna Fay Reviewers: Luiza Radu Sara Meunier Jojo Jiang Alexander Arnold Brienne McLane* Phillip Stokes* *MD at time of publication
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
First published Mar 10, 2014, updated Sept 29, 2024 on www.thecalgaryguide.com