damage occurring in the context of mTBI, and [the results] underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations.”
Editor’s Note: People should be aware of these findings, which confirm earlier studies, and begin rehabilitative treatment as soon as possible after a concussion. New research should target white matter tract changes, with the goal of secondary prevention, i.e. limiting damage to the brain after a traumatic injury has occurred. There are several promising drugs that can prevent damage if administered immediately after an mTBI, including the antioxidant supplement N-acetylcysteine (NAC), which has shown promise in preliminary clinical and laboratory studies, and many others, including lithium and valproate, as reported by De-Maw Chuang and this editor Robert M. Post in a 2015 article in the Journal of Neurology and Stroke titled “Preventing the Sequelae of Concussions and Traumatic Brain Injury.”
5-HT7 is a type of receptor activated by the neurotransmitter serotonin. Some of the most potent effects of lurasidone (Latuda), an atypical antipsychotic with antidepressant effects in bipolar depression, and vortioxetine (Brintellix), a unique antidepressant for unipolar depression that also has positive effects on cognition, occur through the blockade of 5-HT7 receptors. The atypical antipsychotics aripiprazole and sulpiride also act on 5-HT7 receptors.
Researcher Agnieszka Nikiforuk summarized the research to date on 5-HT7 receptors in the journal CNS Drugs in 2015.
The receptors play a role in regulating sleep and circadian rhythms, which may explain why drugs that target them can be helpful in depression. Drugs that target 5-HT7 receptors have also improved learning and memory.
One subject of research into 5-HT7 receptors is whether better results come from blocking the receptors or stimulating them.
Blockade of 5-HT7 receptors has improved depression-like symptoms in animals and enhances the effects of sub-therapeutic doses of antidepressants. In other animal studies, stimulation of the receptors has appeared promising for the prevention of age-related cognitive decline.
Genetic variation in L-type calcium channel genes have been linked to bipolar disorder. Since calcium plays an important role in circadian rhythms, abnormalities in the calcium channel in bipolar disorder could explain some of the circadian rhythm disturbances patients with bipolar disorder exhibit. New research by Michael McCarthy and colleagues shows that calcium channels in general, and the gene CACNA1C in particular, affect signaling pathways that regulate circadian rhythms in both human and animal cells. The researchers also found that calcium channels affected how lithium changes circadian rhythms, suggesting a mechanism by which the treatment may work. They suggest that drugs that affect the L-type calcium channel may be promising treatments for bipolar disorder.
Editor’s Note: The L-type calcium channel blocker nimodipine has had antidepressant, antimanic, and anticycling effects in some patients with bipolar disorder in small studies both by Peggy Pazzaglia and colleagues (including this author Robert Post) and a larger randomized study by Haroon R. Chaudhry.
The clinical effects of nimodipine results thus align with studies linking the CACNA1C gene to bipolar illness and its early onset, increased expression of the gene in the brain of bipolar patients in autopsy studies, increased levels of calcium in white cells of bipolar patients, and a variety of other neurobiological phenomena observed in normal controls carrying the risk gene.
The new link found between CACNA1C and circadian rhythms further links the L-type calcium channel abnormality and bipolar disorder, as well as the therapeutic effects of the L-type calcium channel blocker nimodipine. This drug deserves further study, especially in those with the genetic variation in CACNA1C that has been linked to bipolar disorder.
Both bipolar disorder and unipolar depression often begin in childhood or adolescence, but it can 