Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Abstract

Biological studies of bipolar disorder initially focused on the mechanism of action for antidepressants and antipsychotic drugs, and the roles of monoamines (e.g., serotonin, dopamine) have been extensively studied. Thereafter, based on the mechanism of action of lithium, intracellular signal transduction systems, including inositol metabolism and intracellular calcium signaling, have drawn attention. Involvement of intracellular calcium signaling has been supported by genetics and cellular studies. Elucidation of the neural circuits affected by calcium signaling abnormalities is critical, and our previous study suggested a role of the paraventricular thalamic nucleus. The genetic vulnerability of mitochondria causes calcium dysregulation and results in the hyperexcitability of serotonergic neurons, which are suggested to be susceptible to oxidative stress. Efficacy of anticonvulsants, animal studies of candidate genes, and studies using induced pluripotent stem cell‐derived neurons have suggested a relation between bipolar disorder and the hyperexcitability of neurons. Recent genetic findings suggest the roles of polyunsaturated acids. At the systems level, social rhythm therapy targets circadian rhythm abnormalities, and cognitive behavioral therapy may target emotion/cognition (E/C) imbalance. In the future, pharmacological and psychosocial treatments may be combined and optimized based on the biological basis of each patient, which will realize individualized treatment.

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

“…Thus, these drugs are usually combined with Li for acute treatment and maintenance of bipolar depression. 12 It is noteworthy that patients with BD commonly face residual mood symptoms, cognitive and functional impairment, psychosocial disability, and decreased quality of life even with the best treatment available. 13,14 BD has been suggested as a progressive condition, and the delay in diagnosis as well as inappropriate treatment can result in repeated mood episodes, persistent subthreshold symptoms, development of co-morbidities, and progression of the disease with cognitive impairment and functional decline.…”

Toward the establishment of neurophysiological indicators for neuropsychiatric disorders using transcranial magnetic stimulation‐evoked potentials: A systematic review

“…Specifically, combined TMS-EEG has permitted the development of novel neuromodulation targeted at non-motor areas, 144 suggesting that it can be used for expansion of the range of stimulation protocols. Further elucidation of the effects of neuromodulation on TEP-related biomarkers could be helpful to the application of TMS-EEG as a useful biometric to assess clinical effectiveness in a wide range of neuropsychiatric disorders, including major depression, bipolar disorder, 145 schizophrenia, 146 addiction, autism spectrum disorders, attention deficit hyperactivity disorder, and mild cognitive impairment.…”

<p>Comorbid Premenstrual Dysphoric Disorder in Women with Bipolar Disorder: Management Challenges</p>

“…Furthermore, CBT with sessions of 90 min or more was demonstrated to decrease relapse rate, severity of depression and mania, and to improve psychosocial function, with more enhanced efficacy for BD I than BD II. 92 The authors also strongly suggest combined CBT with neurofeedback treatments. In the same field, a recent systematic review and meta-analysis aiming to address the efficacy of CBT as an adjuvant to pharmacotherapy in BD patients included 19 RCTs, for a total number of 1384 patients with BD-I and BD-II.…”