About this Research Topic
The monoamine hypothesis has dominated the research on the pathophysiology of mood disorders as well as the development of therapeutic drugs by over half a century. Nowadays a change of perspective is taking place. The glutamate system is increasingly implicated in the pathophysiology of mood disorders. The evidence spans from animal, post-mortem, imaging, pharmacological and genome-wide association studies in major depressive disorder (MDD) and bipolar disorder (BD). These disorders have been recently re-conceptualized as a synaptic plasticity-related disorders rather than simply as deficits or excesses in individual neurotransmitters. A paradigm shift from a monoamine hypothesis to a neuroplasticity hypothesis focused on glutamate may represent a substantial advancement in the research for new drugs and therapies. In this context, research into the neuroprotective effects of mood stabilizers and the neuroplasticity effects of glutamatergic psychedelics is becoming increasingly important.
The aim of this Research Topic is to examine the neurobiological mechanisms underlying the glutamatergic hypothesis of mood disorders with a look at the different clinical phenotypes and treatment perspectives related to this paradigm shift. The goal is to shedding light on new paradigms, approaches and data from basic research, as well as clinical and intervention studies in neuroscience, biology, social medicine and psychology.
The neuroplasticity hypothesis of mood disorders stems from the evidence that acute and chronic stress and depression itself lead to glutamate release dysregulation. This dysregulation induces neuronal atrophy and overall synaptic depression in the prefrontal cortex (PFC) and the hippocampus while other cerebral regions, like amygdala, show changes consistent with neuronal hypertrophy and synaptic potentiation. The subsequent fronto-limbic synaptic disconnection is critical to the progress and treatment of mood disorders.
The interplay of glial and glutamatergic system along with stress-induced changes and neuroinflammation, may be deeply involved in the pathogenesis of mood disorders. In this context, the kynurenine (KYN) pathway is becoming increasingly important.
The aim of this Research Topic is also to discuss how drugs that modulate glutamatergic transmission in combination with psychotherapy and psychosocial rehabilitation can act on neuroplasticity. Special attention will be given to studies on ketamine and psychedelics in combination with psychotherapy in treatment-resistant depression and bipolar depression.
We welcome studies on:
• Neurobiological mechanisms underlying the glutamatergic hypothesis of mood disorders (including animal, post-mortem, imaging, pharmacological and genome-wide association studies)
• Neurodevelopmental trajectories across the lifespan susceptible to explain neuroplasticity processes in mood disorders (i.e. longitudinal studies, endophenotypes)
• Interrelationship between neuroinflammation, glia pathology and glutamatergic neurotransmission
• Effects of social interaction and activity on neuroplasticity processes and mood during the lifespan
• Neuroprotective and neuroplasticity effects of mood stabilizers and glutamatergic drugs
• Studies on ketamine and psychedelics for the management of mood disorders
• Effect of the combination of ketamine or psychedelics plus psychotherapy on mood disorders and neuroplastic mechanisms
The aim of this Research Topic is to examine the neurobiological mechanisms underlying the glutamatergic hypothesis of mood disorders with a look at the different clinical phenotypes and treatment perspectives related to this paradigm shift. The goal is to shedding light on new paradigms, approaches and data from basic research, as well as clinical and intervention studies in neuroscience, biology, social medicine and psychology.
The neuroplasticity hypothesis of mood disorders stems from the evidence that acute and chronic stress and depression itself lead to glutamate release dysregulation. This dysregulation induces neuronal atrophy and overall synaptic depression in the prefrontal cortex (PFC) and the hippocampus while other cerebral regions, like amygdala, show changes consistent with neuronal hypertrophy and synaptic potentiation. The subsequent fronto-limbic synaptic disconnection is critical to the progress and treatment of mood disorders.
The interplay of glial and glutamatergic system along with stress-induced changes and neuroinflammation, may be deeply involved in the pathogenesis of mood disorders. In this context, the kynurenine (KYN) pathway is becoming increasingly important.
The aim of this Research Topic is also to discuss how drugs that modulate glutamatergic transmission in combination with psychotherapy and psychosocial rehabilitation can act on neuroplasticity. Special attention will be given to studies on ketamine and psychedelics in combination with psychotherapy in treatment-resistant depression and bipolar depression.
We welcome studies on:
• Neurobiological mechanisms underlying the glutamatergic hypothesis of mood disorders (including animal, post-mortem, imaging, pharmacological and genome-wide association studies)
• Neurodevelopmental trajectories across the lifespan susceptible to explain neuroplasticity processes in mood disorders (i.e. longitudinal studies, endophenotypes)
• Interrelationship between neuroinflammation, glia pathology and glutamatergic neurotransmission
• Effects of social interaction and activity on neuroplasticity processes and mood during the lifespan
• Neuroprotective and neuroplasticity effects of mood stabilizers and glutamatergic drugs
• Studies on ketamine and psychedelics for the management of mood disorders
• Effect of the combination of ketamine or psychedelics plus psychotherapy on mood disorders and neuroplastic mechanisms
Keywords: The glutamate (or neuroplasticity) hypothesis of mood disorders
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