ABSTRACT
Until the mid-nineteenth century, etiological hypotheses on melancholy and depression postulated that these mental disorders were the result of humor dysregulation or mechanical alterations in the correct circulation of biological ¡uids, or were considered diseases of the soul (López-Muñoz et al. 2009a, 2009b). However, the great advances that took place during the second half of the nineteenth century in the ˜eld of neurobiology and in the knowledge of the structure of the nervous system, as well as the positivist mentality of psychiatry of this time, de˜nitely put a stop to these postulates. These developments led to a process called mental illness somatization, in which mental disorders were regarded as products of an organic lesion (Alexander and Selesnick 1970; Huertas 1993). In this condition, the origin of affective disorders was associated, for example, with a local effect on the brain due to a spasm in the dura mater (status striatus), a state of exhaustion or decrease of brain energy, or a hormonal or metabolic alteration (Jackson 1990). But all these changed with the discovery, in the ˜rst half of the twentieth century, of the chemical messengers responsible for interneuronal communication (López-Muñoz and Alamo 2009a) and, especially, with the clinical
6.1 Introduction .......................................................................................................................... 119 6.2 First Advance: Discovery of Neurotransmitters and Chemical Hypothesis of
Neurotransmission ................................................................................................................ 120 6.3 Second Advance: Contribution of Psychotropic Drugs to Neurobiological Research on
Depression ............................................................................................................................ 123 6.3.1 Role of Reserpine ......................................................................................................124 6.3.2 Role of Iproniazid ..................................................................................................... 126 6.3.3 Role of Imipramine and TCAs ................................................................................. 127
6.4 Postulate of Monoaminergic Theories of Depression .......................................................... 128 6.4.1 Catecholaminergic Hypothesis of Depression .......................................................... 129 6.4.2 Serotonergic Hypothesis of Depression .................................................................... 130
6.4.2.1 Pharmacological Contribution of Fluoxetine and Selective Serotonin Reuptake Inhibitors to Serotonergic Hypothesis of Depression ................ 131
6.5 New Integrated Approaches in Etiopathogenic Theories of Depression .............................. 134 6.5.1 New Hypotheses: From Synapse to Intraneuronal Biochemical Pathways .............. 134
6.6 Conclusions ........................................................................................................................... 136 References ...................................................................................................................................... 136
introduction in the 1950s of the main groups of psychotropic drugs still used today, which resulted to a veritable revolution in the ˜eld of psychiatry.
