The neurobiology of bipolar disorder
The article is a theoretical piece as it discusses the neurobiology behind bipolar disorder.
The article focuses on the changes in brain connectivity and neurotransmitter imbalances that underlie the mood states of bipolar disorder. It proposes a new therapeutic approach combining serotonergic and dopaminergic modulation to treat the multiple symptom domains in depression associated with bipolar disorder.
Main topics:
- Altered connectivity in key regions of the brain
- Imbalances in specific neurotransmitters, such as serotonin and dopamine
- Autoreceptor activation and the delayed effect of traditional antidepressant treatments
- New therapeutic approach combining serotonergic and dopaminergic modulation
Secondary topics:
- The role of specific brain regions in manic and depressive moods
- The use of traditional antidepressant medications and their limitations in treating bipolar depression
- The potential side effects of high occupancy levels of d2 blocking agents
The Neurobiology of Bipolar Disorder: A Novel Approach to Treatment
Bipolar disorder is a chronic illness characterized by extreme mood states, including cycling between manic and depressive episodes. The disorder is thought to be caused, in part, by altered connectivity within specific regions of the brain. Increased connectivity in emotional control regions, such as the amygdala and ventrolateral prefrontal cortex, is observed, while decreased connectivity in regions linked to cognitive control, such as the dorsomedial prefrontal cortex, hippocampus, and dorsolateral prefrontal cortex, is found. These alterations underlie both manic and depressive moods.
A specific imbalance of neurotransmitters, such as serotonin, has also been linked to mood dysregulation in bipolar disorder. Traditional antidepressant treatments, which increase synaptic serotonin levels, have limited use in bipolar depression due to the risk of a shift to the manic pole of the disorder. Targeting serotonin modulation not subject to autoreceptor-mediated delay of antidepressant effects, along with presynaptic modulation of dopamine D2/D3 receptors, may offer a novel approach to treating the multiple symptom domains associated with bipolar disorder.
A Novel Therapeutic Approach
A new therapeutic approach targeting serotonergic modulation, combined with presynaptic modulation of dopamine D2/D3 receptors, may represent an alternative and enhanced method of treating bipolar disorder. This approach may also be linked to reduced post-synaptic D2 receptor blockade-mediated effects, which are associated with poor tolerability.
Research has shown that blocking 5-HT7 receptors, a subtype of the serotonin receptor, offers a more rapid onset of antidepressant effects, suggesting this as an alternative approach. Similarly, targeting presynaptic dopamine D2 receptors has been shown to mediate an antidepressant-like effect by increasing dopamine levels and decreasing expression levels of another dopamine receptor subtype, D3, which is increased by antidepressant treatment.
In conclusion, this novel approach to combined serotonergic and dopaminergic modulation may offer an alternative and enhanced method of treating bipolar disorder by targeting the multiple symptom domains associated with the disorder. By avoiding post-synaptic D2 receptor blockade, the approach may also be linked to reduced liability for associated side effects.