رویکردهای سایکو فارماکولوژی عصبی نوظهور
1- Introduction
2- Expanding Views on the Neurobiology of Depression
3- Endocrine Pharmacotherapeutic Targets in Depression
4- Neurosteroid Pharmacotherapeutic Targets in Depression
5- Neuropeptide Pharmacotherapeutic Targets in Depression
6- Pharmacotherapeutic Targets for Depression in Reward Neurocircuits
7- Conclusions
References
Introduction
Depression is one of the most frequent mental disorders in everyday clinical practice and is currently regarded as the leading cause of disability worldwide [1]. In addition to the profoundly debilitating condition of this disorder, major depressive disorder (MDD) entails an increased risk of medical comorbidities [2] and very high direct and indirect financial costs [3]; profiling this disorder as an important problem for public health. In spite of this outlook, pharmacotherapy alternatives for MDD remain insufficient: Currently available antidepressant drugs (AD) have only been shown to achieve remission rates around 56% after four successive treatment stages [4]. Moreover, a majority of the available AD at present display problematic side-effect profiles and a delayed onset of action, further complicating the management of this disorder [5]. 2e development of newer, more effective, and tolerable agents is a pressing matter in neuropsychopharmacology, yet relatively few new drugs have been approved for MDD in recent decades [6]. Both the limited effectivity of existing AD and the scarcity of novel options may stem from a once revolutionary, yet—in retrospect—excessive and misguided focus on the monoamine hypothesis for the pathophysiology of depression, which centers on defective neurotransmission of serotonin (5-hydroxytriptamine, 5HT), noradrenaline (NA), and dopamine (DA) in the brain [7]. Indeed, the serendipitous discovery of tricyclic AD drove the “reverse engineering” of this hypothesis, which in turn has guided much of the development of all AD throughout history [8]. Nevertheless, the monoamine hypothesis has been heavily contested regarding its validity and the relative importance of its components [9, 10]. At present, advances in molecular psychiatry have reframed neuronal monoamine dysregulation to be the end state of a complex interplay among pathophysiologic pathways involving several nonmonoamine neurotransmitters, as well as several endocrinemetabolic components [11]. 2is more holistic understanding of the pathophysiology of MDD has allowed for the design and investigation of novel and promising AD candidates, with activity outside the monoamine dysregulation end state, thus providing provocative windows for intervention [12]. As preclinical and clinical studies progress at various rates for these molecules, this review aims to summarize current views on the neurobiology of depression, with an emphasis on emerging pharmacological targets beyond monoamine neurotransmission.