Table 3.

Rationale for Habenula involvement in psychiatric disorders.

	Depression	Bipolar disorder	Schizophrenia	Obsessive-compulsive disorder
Evidence for involvement of habenula	Animal studies implicate the habenula in depressive-like behavior (45, 67). The LHB is found to be hyperactive and ablation of the habenula in animals alleviates depressive-like symptoms (33, 67) (proulx; Fakhoury). Altered habenula volume and function has been reported in human subjects (58, 68).	Altered habenula volume and function has been reported in human subjects (15, 58, 69). Animal models show involvement of LHB in mood disorders [see Depression].	Altered habenula volume and function has been reported in human subjects (15, 70, 71). Rodent models show LHB function important for guided decision making, and LHB hypoactivity associated with schizophrenia-like symptoms (45, 72). Antipsychotic drugs increase LHB activity in animal model (33)	Encoding and processing of aversive stimuli–processes dependent on the LHB–are impaired in OCD (36, 73, 74). Depressive symptoms are often present in OCD (75). Hb-DBS has previously been used to successfully treat depression (47)
Proposed habenula contribution to the psychiatric disorder and/or symptoms	LHB encodes negative motivational values and aversive outcomes associated with cues (37). Continuously hyperactive LHB causes depressive state (13, 47).	Hyperactive LHB causes depressive state (13, 47) [see Depression].	The habenula plays a key role in controlling the monoaminergic systems and these systems are disturbed in SZ (17, 76). Hypoactive LHB interferes with appropriate guidance of behavior and decision making (45).	Monoaminergic systems are disturbed in OCD and the habenula plays a key role in their control (17, 77).
Proposed mechanism of the beneficial effect of habenula DBS	DBS reduced LHB neuronal activity via GABAb receptors (40, 50).	DBS corrects habenula dysfunction (65) [see Depression].	DBS corrects habenula hypoactivity (63).	DBS corrects habenula dysfunction (64).

DBS, Deep brain stimulation; LHB, Lateral Habenula; OCD, Obsessive-Compulsive Disorder; SZ, Schizophrenia.