The 5-HT1A receptor in Major Depressive Disorder

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• This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030.

• specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD.

• There are currently several theories that seek to explain the underlying pathophysiology of MDD. One such theory, known as the monoamine deficiency hypothesis of depression, proposes that a deficiency in monoanmine neurotransmission (serotonin, norepinephrine and dopamine) in the central nervous system (CNS) underlies the development of MDD (Belmaker and Agam, 2008, Schildkraut, 1965).

• The main finding of this study was that subjects who had attempted suicide had significantly lower levels of CSF 5-HIAA than controls, with a more pronounced reduction in the metabolite if the suicide attempt was violent.

• Further credence for the monoamine deficiency hypothesis is provided by the fact that the three classes of antidepressants currently used to treat MDD i.e. monoamine oxidase inhibitors, tricyclic antidepressants and selective serotonin reuptake inhibitors (MAO-I, TCA and SSRI, respectively) all act by increasing the amount of serotonin present in the synaptic cleft by either inhibiting its synaptic reuptake or by inhibiting its metabolism