Pathobiological targets of depression.
BACKGROUND
Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression.


METHODS
The various pathological factors involved in depression are: monoamine hypothesis, neurotransmitter receptor hypothesis, neurotrophic factor hypothesis, hypothalamic-pituitary-adrenal (HPA) dysregulation, oxidative stress, cytokine hypothesis and NO pathway. Recent drug therapies used to treat depression include: selective serotonin re-uptake inhibitors, norepinephrine and dopamine re-uptake inhibitors and several herbal drugs. The present review focuses on recently unraveled pathogenetic hypotheses and therapeutics of mental depression. Moreover, various evaluation models for antidepressants are discussed.


CONCLUSIONS
Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160014, India. dr_chopra_k@yahoo.com
Kanwaljit
K
Chopra
Baldeep
B
Kumar
Anurag
A
Kuhad
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D058990:Molecular Targeted Therapy; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction
D000928:Antidepressive Agents; D016207:Cytokines; D009569:Nitric Oxide; D007737:Kynurenine