Kapur S, Mann JJ. Role of the dopaminergic system in depression. Biol Psychiatry 32: 1-17
Department of Psychiatry, University of Pittsburgh School of Medicine, PA. Biological Psychiatry
(Impact Factor: 10.26).
08/1992; 32(1):1-17. DOI: 10.1016/0006-3223(92)90137-O
A hypothesis implicating dopamine in depression was proposed over 15 years ago (Randrup et al 1975). The identification of multiple new subtypes of dopamine receptors and evolving views regarding the function of the dopamine systems in the brain require a reexamination of this hypothesis. Results from studies in depression, Parkinson's disease, and animal models of depression suggest a deficiency of dopamine in depression. Dopamine precursors, dopamine agonists, and dopamine reuptake inhibitors show therapeutic efficacy in depression. Electroconvulsive therapy (ECT) and standard pharmacological antidepressants enhance dopamine function. Studies using receptor-specific drugs in clinical trials and neuroimaging studies are needed to further clarify the role of dopamine in depression.
Available from: Sunao Kaneko
- "The most commonly accepted explanation is that ECT enhances dopaminergic transmission. This enhancement may occur at the receptor or postreceptor level.17 Animal studies have demonstrated an upregulation of the GABAergic system. "
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Tardive dystonia and dyskinesia are potentially irreversible neurological syndromes. Successful electroconvulsive treatment (ECT) has been reported by multiple sources; however, the existing retrospective reviews and open prospective trials provide little information on the response rate.
Eighteen consecutive patients with tardive dystonia or dyskinesia received a standard course of ECT to treat abnormal movement. The severity of the tardive dystonia and dyskinesia was evaluated using the Abnormal Involuntary Movement Scale (AIMS) before and after the course of ECT. The patients who displayed a greater than 50% improvement in the AIMS score were classified as the responders.
The mean AIMS score decreased from 19.1±4.7 to 9.6±4.2. There were seven responders among the 18 patients, which yielded a 39% response rate.
ECT has a moderate but significant effect on tardive dystonia and dyskinesia.
Neuropsychiatric Disease and Treatment 07/2014; 10:1209-12. DOI:10.2147/NDT.S62490 · 1.74 Impact Factor
Available from: Salvatore Salomone
- "Indeed, the hypofunction of the mesolimbic dopaminergic pathway is responsible for anhedonia , one of the major symptoms of depression, which is scarcely affected by SSRI treatment (Kulkarni and Dhir, 2009; Willner, 1983). Worthy of note, homovanillic acid, the major metabolite of dopamine, is decreased in the cerebrospinal fluid of depressed patients (Brown and Gershon, 1993; Kapur and Mann, 1992). Different antidepressant drugs can affect dopaminergic neurotransmission: desipramine increases dopamine levels in the frontal "
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ABSTRACT: A substantial proportion of depressed patients do not respond to current antidepressant drug therapies. So far, antidepressant drugs have been developed based on the "monoaminergic hypothesis" of depression, which considers a synaptic deficiency in 5-hydroxytryptamine (5-HT; serotonin) or noradrenaline as main cause. More recently, the dopaminergic system has been implicated in the efficacy of some antidepressants, such as desipramine, amineptine, nomifensine. Dysfunction of dopaminergic neurotransmission within the mesolimbic system may contribute to anhedonia, loss of motivation and psychomotor retardation in severe depressive disorders. Dopamine D3 receptor subtype is located both pre- and postsynaptically in brain areas regulating motivation and reward-related behavior and has been implicated in depression-like behaviors. Activity of mesolimbic dopamine neurons in the reward circuit is a key determinant of behavioral susceptibility/resilience to chronic stress, which plays a central role in the pathogenesis of depression. Dopamine D3 receptor expression and function are both down-regulated in stress and depression, and these changes are reversed by antidepressant treatments, suggesting that enhanced dopaminergic neurotransmission mediated by dopamine D3 receptor participates in adaptive changes related to antidepressant activity. Of note, brain derived neurotrophic factor (BDNF) controls the expression of the dopamine D3 receptor in some brain areas and BDNF induction by antidepressant treatments is related to their behavioral activity. A number of experimental drugs in pre-clinical or clinical development, including aripiprazole and cariprazine, may act as antidepressants because of their partial agonist activity at dopamine D3 receptors. These preclinical and clinical data are discussed in the present review.
European journal of pharmacology 07/2013; 719(1-3). DOI:10.1016/j.ejphar.2013.07.022 · 2.53 Impact Factor
Available from: Ryan Bogdan
- "The second factor is an alteration in participants’ ability to learn from reward feedback. This is emphasized by preclinical animal models of depression [19-22] and, because of the close association between dopamine (DA) signalling and reward learning [23-27], by neurobiological accounts linking anhedonia to DA [11,14,28-35]. It is most important to separate these factors, since they are likely to be associated with radically different ætiologies and therapeutic routes. "
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Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge.
Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate.
MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate.
Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior.
Biology of Mood and Anxiety Disorders 06/2013; 3(1):12. DOI:10.1186/2045-5380-3-12
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