Transcranial direct current stimulation (tDCS) for treatment-resistant psychosis

Neurostimulation techniques are a growing aspect of psychiatric treatment especially as advances in pharmacotherapy have slowed down. Although electroconvulsive therapy (ECT) remains the best studied and perhaps most efficacious form of neurostimulation for treatment-resistant psychosis and mood disorders, it is invasive, requires considerable resources, and remains stigmatized. tDCS by contrast is noninvasive, requires few resources, and has never been portrayed as a form of punishment in novels and films. Although its efficacy for psychosis is yet to be fully established, evidence is accumulating. Because tDCS is relatively easy to administer, controlled experiments with active and sham treatment groups are feasible.

tDCS involves the passage of an electrical current of 1-2 milliamperes across the cerebral cortex by means of 2 electrodes placed on the scalp. To diminish auditory hallucinations, electrodes are placed on the left fronto-temporal region; for negative symptoms, bifrontal placement has been used. The treatment is typically given for 20 minutes twice a day for at least 5 days. Adverse effects are minimal but may include tingling or itching at the site of electrode placement and short-lived somnolence.

According to a review by Mondino, Fecteau and colleagues, 32 studies have examined the effects of tDCS in schizophrenia. Most studies involved patients who were also receiving medication, and several case reports have described safe combination with clozapine. For auditory hallucinations, 14 studies exist including 2 randomized controlled trials (RCTs) which included a total of 54 patients. One RCT found a 30% reduction in treatment-resistant auditory hallucinations after 10 sessions, significantly greater than in the sham-treatment group. The second RCT, however, did not find a significant reduction in auditory hallucinations. The treatment parameters differed between the studies, which confounds interpretation; for instance, in the positive trial, subjects received tDCS twice daily whereas in the negative trial, tDCS was once daily.

In the review, the authors also describe investigations of tDCS on such parameters as functional MRI, auditory and motor evoked potentials, and cognitive measures including executive function. Questions yet to answered include the appropriate duration of each tDCS session, 20 minutes being the most usual; the total duration of treatment, i.e. days or weeks; and the placement of electrodes. The duration of beneficial effect is uncertain, although data to date suggest it may endure for several months, and the role of maintenance treatment requires considerable investigation.

Reference

Mondino M, Brunelin J, Palmc U, Brunonid AR, Pouleta E and Fecteau S. Transcranial direct current stimulation for the treatment of refractory symptoms of schizophrenia: current evidence and future directions. Current Pharmaceutical Design. 2015;21:3373-3383. Abstract

Health Care is a Human Right

On July 19th, 2014, Dr. Randall White was invited to speak at  The Western Washington Chapter of Physicians for a National Health Program’s Ninth Annual Public Meeting. This year’s theme was: “Health Care is a Human Right: Making it Real in Washington State.” As a physician who has practiced both in Canada and the US, Randall brings a unique perspective to the table. Dr. White is a known advocate for health care equality, and stresses that financial access to health care is a major source of inequality. He says “Inequality has greater effects on Health Care than the actions of doctors and caregivers. In Canada, Health Care is a human right.” He goes on to encourage his American colleagues to continue to strive for universal health care.

MicroRNA: a new frontier in schizophrenia?

A large consortium of researchers in Europe, North American and Australia performed a genome-wide association study (GWAS) of single-nucleotide polymorphisms, which are uncommon variants of genes, among people with schizophrenia in two stages. In the first stage, a discovery analysis of pre-existing GWAS cohorts, they included, 9,394 people with schizophrenia and 12,462 controls, all of European ancestry. In the second-stage independent replication, they used a sample of 8,442 cases and 21,397 controls. In the combined stage-1-and-2 dataset, five alleles had a significant and novel association with schizophrenia, whereas two alleles identified in previous research had significant association. The most robustly newly associated allele was rs1625579 on chromosome 1p21.3, in intron 3 of AK094607. This region codes for the primary transcript of MIR137, a microRNA involved in adult neurogenesis and neuronal maturation. Two previous studies cited in the present report found an association of this regulatory mechanism with schizophrenia. Moreover, four genes identified as possibly associated with schizophrenia in the present study are targets of MIR137.

Although the evidence is circumstantial, the researchers assert a possible pathophysiologic role for the MIR137 mechanism in schizophrenia. Linkage studies, an older approach to identify candidate genes, have identified schizophrenia-related genes such as DISC1, and studies of patients with copy-number variants such as 22q11 deletion syndrome have suggested additional genetic etiologies of psychosis. The heterogeneity of “the group of schizophrenias,” as Bleuler called this disorder (2), is being borne out in genetic research, and psychiatrists should pay attention. We can hope that such work will bear fruit in improved treatments for our patients.

References

1. The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium. Genome-wide association study identifies five new schizophrenia loci. Nat Genet. 2011.18;43:969-976. Full text

2. Bleuler, Eugen. Dementia praecox or the group of schizophrenias. Leipzig, Germany; 1911.