The monoamine hypothesis has dominated research into the pathophysiology and pharmacotherapy of depression for a long time. Monoamine hypothesis of major depression was formulated almost half a century ago, 21 which stated that deficiency of monoamine neurotransmitters, namely, norepinephrine andor serotonin, underlies clinical depression. In the 1950s the monoamine oxidase inhibitors maois and tricyclic antidepressants were accidentally discovered to be effective in the treatment of depression. History and evolution of the monoamine hypothesis of depression.
Pdf on jan 1, 2019, fiammetta cosci and others published the monoamine hypothesis of depression revisited. This hypothesis proposes that depression results from decreased neurotrophic support, leading to neuronal atrophy, decreased hippocampal neurogenesis and loss of glia, and that antidepressant treatment blocks or reverses this neurotrophic factor deficit, and thereby reverses the. The monoamine hypothesis, which suggests a deficiency or imbalances in the monoamine neurotransmitters, such as serotonin, dopamine and. Oct 08, 2018 it could thus be shown, for example, that depression is associated with decreased serotonin transporter binding in the midbrain and amygdala gryglewski et al. The main biochemical theory of depression is the monoamine hypothesis, which states that depression is caused by a functional deficit of monoamine transmitters at certain sites in the brain, while mania results from a functional excess. Monoamine hypothesis depression and neurotransmitters. Depression may be caused by a stressinduced deficiency in monoaminergic activation of genes that code for neurotrophic factors.
Beyond the monoamine hypothesis cambridge university press. Some dopaminergic drugs have also been successfully in the treatment of depression. Mar 27, 2021 neurotransmitter hypothesis of depression. Two structurally unrelated compounds developed for nonpsychiatric conditions, namely iproniazid and imipramine, had potent antidepressant effects in humans. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic andor serotonergic. Novel medications targeting non monoaminergic neurotransmitters offer the hope of improved treatments. The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine, andor dopamine in the central nervous system. The serotonin hypothesis in 1965, joseph schildkraut put forth the hypothesis that depression was associated with low levels of norepinephrine 6, and later researchers theorized that serotonin was the neurotransmitter of interest 7. The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis ofdepression is a depletion in the levels of serotonin, norepinephrine, andor dopamine in the centralnervous system. Implications for monoamine hypothesis of depression core. The monoamine hypothesis has long been recognized as a core concept in the pathogenesis of depression. The norepinephrine link but which monoamines were most important in depression. The dopamine hypothesis of schizophrenia and the emphasis on other neurotransmitters, most notably norepinephirne, serotonin, and acetylcholine, in the pathogenesis of depression, have focused attention away from substantial evidence implicating dopamine in affective disorders.
The connexion scientists made between an improved mood in patients with tuberculosis and higher levels of monoamines in their brains led to further research into mao inhibitors maois as a treatment for depression lopezmunoz et al. Monoamine theories associate depression with reduced brain monoamine levels. However, evolving research has shown that the classic monoamine hypothesis of depression i. This finding led to the adoption of the monoamine hypothesisof depression, first put forward over 30 years ago, which proposes that the underlying biologicalor neuroanatomical basis for depression is a deficiency of central noradrenergic andorserotonergic. Depression monoamine hypothesis psychology wiki fandom. Chronic depression new antidepressants antidepressant medication the monoamine hypothesis snaris, nassas, and naris new ways to treat depression the neurobiology of depression pdf monoamines and novel antidepressants mood enhancement via stem cell therapy the future of depression psychopharmacology. Many antidepressant drugs acutely increase synaptic levels of the monoamine neurotransmitter, serotonin, but they may also enhance the levels of norepinephrine and serotonin.
The functional deficiency of noradrenergic transmission in depression was, then, inferred from the effects of imipraminelike drugs and monoamine oxidase inhibitors on catecholamine metabolism, since both these types of drugs increase catecholamine at adrenergic receptor sites. This mainstream story has been undermined by a failure to prove the monoamine deficiency hypothesis or any other theory of mdd,3,6 longstanding concerns about a high falsepositive rate in. This has led to the development of antidepressants that are now more selective than the early tri and tetracyclics from which they have evolved. Apr 25, 2016 although the monoamine theory still circulates in laymen conversation, modern science has largely discredited the simplistic idea, and is moving towards a more manyfactored, immunitycentric model of depression. The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis which can be traced back to the 1950s, which states that depression is due to an imbalance most often a deficiency of the monoamine neurotransmitters namely serotonin, norepinephrine and dopamine. The symptoms of depression can be improved by agents that act by various mechanisms to increasesynaptic concentrations of monoamines. Understanding the role of neurotransmitters in the. These theories achieved broad popularity in the mid1960s. Antidepressant activity monoamine hypothesis new diagnostic method original compound. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic andor serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal. History and evolution of the monoamine hypothesis of. Aug 30, 2018 monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. In subsequent years, there were numerous attempts to identify reproducible neurochemical. Ultimately iproniazid was fda approved as our first.
Hypothesis, in which increased brain 5ht release was found to be associated with central fatigue 26,27. Nevertheless, the imperfect results obtained in clinical practice with currently available antidepressant drugs have propelled the discovery of various potential pharmacological targets beyond noradrenaline, dopamine, and serotonin. In the 1950s, the amine hypothesis of depression was proposed after it was observed that patients treated for hypertension with reserpine developed depression. Understanding depression pathophysiology is challenging because varying depression symptomatology cannot be explained by single hypothesis. However, neither the classical monoamine theory of depression nor the modern hypothesis of the hypersensitivity of postsynaptic excitatory receptorsinhibitory.
Current neuropsychopharmacological approaches to depression are centered on the monoamine hypothesis. The monoamine hypothesis of depression dates to 1952 when both reserpine used to treat hypertension and iproniazid used to treat tuberculosis were shown to increase brain levels of the monoamines serotonin, norepinephrine and dopamine, and simultaneously treated symptoms of depression. The origins of the monoamine hypothesis of depression ness labs. The monoamine hypothesis of depression revisited chapter 7 65 36. Understanding the role of neurotransmitters in the treatment. Ap an unec committed suorters of the mental health treatment community. The monoamine hypothesis is a theory that suggest that clinical are due to a particular chemical imbalances in neurochemistry in the brain of monoamines, such as dopamine, serotonin, and norepinephrine this hypothesis has been a major focus of research in the fields pathophysiology and pharmacotherapy for over 25 years and led to the development of new classes of drugs such as ssris. Conventional psychiatric medications for depression target monoaminergic neurotransmitters with limited benefit. History and evolution of the monoamine theory of depression. Norepinephrineserotonin agonists, and, finally ssris act as serotonin 5ht agonists. Schildkraut of harvard university cast his vote with norepinephrine in the now classic catecholamine hypothesis.
Molecular neurobiology and promising new treatment in. The monoamine hypothesis of depression is an incomplete explanation for understanding and treating depression. The monoamine hypothesis of depression predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin. The monoamine hypothesis of depression is that depression is a result of under activity of monoamines especially serotonin.
Ne regulation of 5ht release monoamine interactions. The hypothesis prompted researchers to investigate the role of 5ht in exerciseinduced central fatigue 2833. This hypothesized pathophysiology appears to be supported by the mechanism of action of antidepressants. Alternative hypotheses such as those involving adult neurogenesis or components of the hypothalamicpituitaryadrenal hpa. This hypothesis is quite simple and easily understandable. The observation of this efficacy led to the monoamine hypothesis of depression. Still, the monoamine hypothesis does not address key issues such as why antidepressants. Reserpine drug that reduces monoamine levels induces depression first monoamine oxidase inhibitors which block metabolism of monoamines and increase brain levels alleviated depression first.
The neurotrophic hypothesis of depression postulates that neuronal plasticity is a key factor in the development of depression and in the clinical response to antidepressants. Early attempts to evaluate monoamine systems in depressive disorders led to diverse and not clearly integratedfindings. Sep 19, 2017 the monoamine hypothesis is the most common of such hypotheses of the pathophysiology of mdd. Beyond the monoamine hypothesis psychu is suorte y tsua pharmaceutical eveloment ommercialiation nc. This insight led to the development of monoamine oxidase inhibitors as the.
Although the monoamine hypothesis in its simple form is insufficient as an exp lanation of depression. Apr 02, 2018 understanding depression pathophysiology is challenging because varying depression symptomatology cannot be explained by single hypothesis. Monoamines are neurotransmitters that include serotonin, dopamine, norepinephrine, and epinephrine monoamine hypothesis of depression. Looking beyond the monoamine hypothesis touchneurology. One theory is that continual stress can lead to dysfunction of this feedback mechanism, resulting in sustained elevations in cortisol that decreased secretion of brainderived neurotrophic factor nbdnf, which causes further damage to hippocampal neurons, thereby contributing to some of the cognitive abnormalities seen with depression. The monoamine hypothesis has been accepted as the most common hypothesis of major depressive disorder mdd for a long period because of its. It has been almost 50 years since the monoamine hypothesis of depression was articulated. The neurobiology of depression oxford academic journals. The origins of the monoamine hypothesis of depression. The monoamine hypothesis is the most common of such hypotheses of the pathophysiology of mdd. Knocking the monoamine theory from the center stage of depression has marked a fundamental change in the field of psychology, and. The clinical evidence includes alterations in depressive symptoms with aging concomitant with possible changes in.
Scientific studies have found that different brain areas show altered activity in people with major. To provide a survey of the current scientific view regarding the neurotrophic hypothesis of depression. These findings and other supporting evidence led joseph schildkraut to publish his paper called the catecholamine hypothesis of affective disorders in 1965. This finding led to the adoption of the monoamine hypothesisof depression, first put forward over 30 years ago, which proposes that the underlying biologicalor neuroanatomical basis for depression is a deficiency of central noradrenergic. This hypothesis proposes that depression results from decreased neurotrophic support, leading to neuronal atrophy, decreased hippocampal neurogenesis and loss of glia, and that antidepressant treatment blocks or reverses this neurotrophic factor deficit, and thereby reverses the atrophy and cell loss 6. In the 1950s it was noticed that around 20% of those patients prescribed the drug reserpine, used at the time. Early attempts to evaluate monoamine systems in depressive disorders led to diverse and not clearly inte. Brainderived neurotrophic factor bdnf is an important protein in this process. Monoamine theory of depression exposed as incomplete, simplistic. Blue genes and the monoamine hypothesis of depression. The monoamine hypothesis of depression, which posits that depression is caused by decreased monoamine function in the brain, originated from early clinical observations 14,20. Since that time, pharmacologic therapy for treatment of depression has focused on increasing concentrations of brain monoamines, namely. A brief history of the development of antidepressant drugs. Pdf the monoamine hypothesis of depression revisited.
The pharmacology of antidepressants is not entirely clear. Although the monoamine hypothesis in its simple form is insufficient as an exp lanation of depression, pharmacological manipulation of monoamine transmission remains the most successful. Molecular neurobiology and promising new treatment in depression. The main limitation for the monoamine hypothesis of depression is the therapeutic lag between initiation of antidepressant treatment and perceived improvement of symptoms. The monoamine theory of depression and drugs acting on monoamine neurotransmission has dominated the treatment of depression for over 30 years. Nevertheless, views on the pathophysiology of depression have evolved notably, and the. The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines.
Beyond neuroanatomy and monoamine theory, we discuss cells and. Apr 25, 2001 the monoamine hypothesis has dominated our understanding of depression and of pharmacological approaches to its management and it has produced several generations of antidepressant agents, ranging from the monoamine oxidase inhibitors maois, through tricyclics tcas and selective serotonin reuptake inhibitors ssris, to the recently introduced selective noradrenaline reuptake inhibitor nari, reboxetine. One explanation for this therapeutic lag is that the initial increase in synaptic serotonin is only temporary, as firing of serotonergic neurons in the dorsal raphe adapt via. Sadness and low mood will be used to refer to a range of negative emotions that would not be classified as mdd. One theory of depression is that it may arise from a deficit or underactivity in the brain of monoamine signaling dopamine da, serotonin 5ht, and norepinephrine ne 1 deficiency in monoaminergic neurotransmission may be in the monoamine levels themselves, or through disrupted receptor signaling. Monoamine hypothesis of major depression was formulated almost half a century ago,21 which stated that deficiency of monoamine neurotransmitters, namely, norepinephrine andor serotonin, underlies clinical depression. The main limitation for the monoamine hypothesis of depression is the therapeutic lag. Indeed, the monoamine reuptake inhibitors and the maois were shown to have antidepressant activity by chance, and the discoveries of their modes of action were. This hypothesis was first started when doctors noticed that reserpine, a monoamine antagonist, was causing depression as a common side effect. Besides the fact that antidepression drugs are all monoamine agonists, there is other evidence that supports the theory. For many years, the prevailing hypothesis of depression has been that a deficit in monoamine neurotransmitters, notably norepinephrine and serotonin. We have also stur died the effects of monoamine depletion sd on depressive.
Monoamine theory of depression exposed as incomplete. The monoamine oxidase inhibitors increase brain concentrations of norepinephrine while imipraminelike agents potentiate the physiological effects of norepinephrine. Effects of monoamines and antidepressants on astrocyte. Blue genes and the monoamine hypothesis of depression stephen m. Is it time to reassess the bdnf hypothesis of depression. Reserpine, a drug which can cause clinical depression, depletes catecholamines, but other amines may also be involved in its mechanism of action. Therefore, they knew that monoamine agonist decrease depression, but they can also induce depression.
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