The different brain centres involved in major depression and the derived pharmcological options

Introduction: In major depression, hypoactivity of monoamines, namely of serotonin, noradrenaline and dopamine and hyperactivity of γ-aminobutyric acid (GABA) and glutamate in the midbrain and the hippocampus can be found. Besides, increased concentrations of the corticotropin-releasing factor (CRH) in the hypothalamus with an enhanced dexamethasone/CRH test can be found in depressive patients.

Material/Methods: The neuronal networks can be described as follows: In the hippocampus, dopaminergic neurons transmit a weak activating impulse via D2 receptors to glutaminergic neurons which strongly inhibit serotonergic neurons through NMDA (N-methyl-D-aspartate) receptors. The serotonergic neurons transmit a weak postsynaptic impulse to GABAergic neurons via 5-HT2C receptors which strongly inhibit dopaminergic neurons via GABAA receptors. The glutaminergic and GABAergic neurons send projections to corresponding neurons in the center of the circadian rhythm in the midbrain. In the „mood center“, noradrenergic neurons transmit a weak activating impulse via α1 receptors to glutaminergic neurons which strongly inhibit serotonergic neurons via the subtype 5 of the metabotropic glutaminergic receptors (m5GluR). The serotonergic neurons transmit a weak postsynaptic impulse via 5-HT1A receptors to GABAergic neurons which strongly inhibit noradrenergic neurons through GABAB receptors. In the hypothalamus, CRH containing neurons which have a high activity transmit a strong activating impulse through CRH1 receptors to glutaminergic neurons which inhibit serotonergic neurons in the dorsal raphe nucleus via m5Glu receptors and reduce serotonin levels.

Results: Derived from the neuronal networks, the following drugs can be administered:

• selective or combined monoamine reuptake inhibitor, while the dopamine and noradrenaline reuptake inhibitor bupropion has an improved antidepressant effect, but cannot be used in disorders with dopamine hyperactivity, e.g. mania or schizophrenia,

• GABAB antagonists or mGluR antagonists, which enhance noradrenaline or serotonin levels,

• 5-HT1A or 5-HT2C agonists,

• α1 or D2 agonists,

• CRH1 receptor antagonists, which enhance serotonin levels through a reduced glutaminergic presynaptic inhibition via m5Glu receptors have been shown to have a small clinical effect.

Conclusion: It is important to examine neuronal networks in major depression so as to make clearer the coherence of the involved neurotransmitters and neuropetides.