Harleen Chhabra

Transcranial direct current stimulation in schizophrenia.

Transcranial direct current stimulation (tDCS) is an upcoming treatment modality for patients with schizophrenia. A series of recent observations have demonstrated improvement in clinical status of schizophrenia patients with tDCS. This review summarizes the research work that has examined the effects of tDCS in schizophrenia patients with respect to symptom amelioration, cognitive enhancement and neuroplasticity evaluation. tDCS is emerging as a safe, rapid and effective treatment for various aspects of schizophrenia symptoms ranging from auditory hallucinations-for which the effect is most marked, to negative symptoms and cognitive symptoms as well. An interesting line of investigation involves using tDCS for altering and examining neuroplasticity in patients and healthy subjects and is likely to lead to new insights into the neurological aberrations and pathophysiology of schizophrenia. The mechanistic aspects of the technique are discussed in brief. Future work should focus on establishing the clinical efficacy of this novel technique and on evaluating this modality as an adjunct to cognitive enhancement protocols. Understanding the mechanism of action of tDCS as well as the determinants and neurobiological correlates of clinical response to tDCS remains an important goal, which will help us expand the clinical applications of tDCS for the treatment of patients with schizophrenia.

Insight facilitation with add-on tDCS in schizophrenia

Impaired insight in schizophrenia patients has been linked with prefrontal deficits. In this open-label study, we examined for potential insight facilitation effects of add-on tDCS (with anodal stimulation of left DLPFC and cathodal stimulation over left temporo-parietal junction) in schizophrenia patients (N=21) with persistent auditory hallucinations despite adequate antipsychotic treatment. Following tDCS, there was a significant improvement in insight with concurrent significant reduction in auditory hallucination severity. Improvement in insight correlated significantly with improvement in severity of auditory hallucinations. These findings suggest improvement of insight with add-on tDCS in schizophrenia with persistent auditory hallucinations.

Transcranial direct current stimulation and neuroplasticity genes: implications for psychiatric disorders

Background and Aim Transcranial direct current stimulation (tDCS) is a non-invasive and well-tolerated brain stimulation technique with promising efficacy as an add-on treatment for schizophrenia and for several other psychiatric disorders. tDCS modulates neuroplasticity; psychiatric disorders are established to be associated with neuroplasticity abnormalities. This review presents the summary of research on potential genetic basis of neuroplasticity-modulation mechanism underlying tDCS and its implications for treating various psychiatric disorders. Method A systematic review highlighting the genes involved in neuroplasticity and their role in psychiatric disorders was carried out. The focus was on the established genetic findings of tDCS response relationship with BDNF and COMT gene polymorphisms. Result Synthesis of these preliminary observations suggests the potential influence of neuroplastic genes on tDCS treatment response. These include several animal models, pharmacological studies, mentally ill and healthy human subject trials. Conclusion Taking into account the rapidly unfolding understanding of tDCS and the role of synaptic plasticity disturbances in neuropsychiatric disorders, in-depth evaluation of the mechanism of action pertinent to neuroplasticity modulation with tDCS needs further systematic research. Genes such as NRG1, DISC1, as well as those linked with the glutamatergic receptor in the context of their direct role in the modulation of neuronal signalling related to neuroplasticity aberrations, are leading candidates for future research in this area. Such research studies might potentially unravel observations that might have potential translational implications in psychiatry.

Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients

Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotics affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia.

Response to Transcranial Direct Current Stimulation in a Case of Episodic Obsessive Compulsive Disorder.

To the Editor: R e. “500-mA ECT—A Proof of Concept Report” by Prashanth Mayur, Anthony Harris, and Bangalore Gangadhar, published as Letter to the Editor on Journal of ECT: June 2015, Volume 31, Issue 2: p e23–e26, I would like to question the methodology involved. In the text, the authors claim that 500 mA pulses are less effective than 800 mA and question that “other ECT parameters may have to be increased to maintain the total energy delivered to the patient to obtain a well-formed seizure on electroencephalogram”; they also claim that “it is not clear if the amplitude reduction resulted in a stimulus dose that was significantly suprathreshold.” My problem with this approach and conclusions is that brief pulse machines, like the MECTA spECTrum 5000Q (MECTA Corporation, Lake Oswego, Ore) they used, allow for a complete control of the electrical stimulus being used. Total electrical charge ismeasured inmillicoulombs (mC), calculated by multiplying the 4 parameters of the brief pulse and then by 2 in biphasic machines (like the one they use, as can be easily verified by the reported parameters). Not only “other ECT parameters may have to be increased” but “other ECT parameters should have been increased” to compensate for lower amperage. To reduce amperage without this compensation created 2 variables influencing the result: lower dosage and different amperage. The authors themselves state that the patients had titrated seizure thresholds (ST) of 19.2 and 72 mC and were being treated with a dosage of 115.2 and 432 mC (6 times above ST), respectively. This means that the stimulus given by the 500 mA pulses of 72 and 270 mC were as follows: a) lower dosages and b) 3.75 times above ST.

Functional near infra-red spectroscopy (fNIRS) in schizophrenia: A review

The research on the alterations in functional connectivity in schizophrenia has been facilitated by development of an array of functional neuroimaging techniques. Functional Near Infra Red Spectroscopy (fNIRS) is a novel diffuse optical neuromonitring method with its own advantages and limitations. The advantages of fNIRS have made it to be frequently used as a research tool by medical community in different settings. In fNIRS the property of haemoglobin to absorb near infrared light is used to measure brain activity. It provides the indirect measurement of the neuronal activity in the areas of interest. The advantage of fNIRS being less restrictive has made it to be used more commonly in the research of psychiatric disorders in general, schizophrenia in particular. The fNIRS studies on patients with schizophrenia have shown haemodynamic hypo activation primarily in the prefrontal cortex during various cognitive tasks. In this review, initially we have briefly explained the basic principles of fNIRS followed by detailed review of fNIRS findings in patients with schizophrenia.

Acute effects of 3G mobile phone radiations on frontal haemodynamics during a cognitive task in teenagers and possible protective value of Om chanting

Abstract Mobile phone induced electromagnetic field (MPEMF) as well as chanting of Vedic mantra ‘OM’ has been shown to affect cognition and brain haemodynamics, but findings are still inconclusive. Twenty right-handed healthy teenagers (eight males and 12 females) in the age range of 18.25 ± 0.44 years were randomly divided into four groups: (1) MPONOM (mobile phone ‘ON’ followed by ‘OM’ chanting); (2) MPOFOM (mobile phone ‘OFF’ followed by ‘OM’ chanting); (3) MPONSS (mobile phone ‘ON’ followed by ‘SS’ chanting); and (4) MPOFSS (mobile phone ‘OFF’ followed by ‘SS’ chanting). Brain haemodynamics during Stroop task were recorded using a 64-channel fNIRS device at three points of time: (1) baseline, (2) after 30 min of MPON/OF exposure, and (3) after 5 min of OM/SS chanting. RM-ANOVA was applied to perform within- and between-group comparisons, respectively. Between-group analysis revealed that total scores on incongruent Stroop task were significantly better after OM as compared to SS chanting (MPOFOM vs MPOFSS), pre-frontal activation was significantly lesser after OM as compared to SS chanting in channel 13. There was no significant difference between MPON and MPOF conditions for Stroop performance, as well as brain haemodynamics. These findings need confirmation through a larger trial in future.

Effect of transcranial direct current stimulation on prefrontal inhibition in schizophrenia patients with persistent auditory hallucinations: A study on antisaccade task performance

Background: Deficient prefrontal cortex inhibitory control is of particular interest with regard to the pathogenesis of auditory hallucinations (AHs) in schizophrenia. Antisaccade task performance is a sensitive index of prefrontal inhibitory function and has been consistently found to be abnormal in schizophrenia. Methods: This study investigated the effect of transcranial direct current stimulation (tDCS) on antisaccade performance in 13 schizophrenia patients. Results: The tDCS resulted in significant reduction in antisaccade error percentage (t = 3.4; P = 0.005), final eye position gain (t = 2.3; P = 0.042), and AHs severity (t = 4.1; P = 0.003). Conclusion: Our results raise the possibility that improvement in antisaccade performance and severity of AH may be mechanistically related.

Telomere length and its association with hippocampal gray matter volume in antipsychotic-naïve/free schizophrenia patients

Accelerated ageing processes are postulated to underlie schizophrenia pathogenesis. This postulate is supported by observations of reduced telomere length in schizophrenia patients. Hippocampus, one of the most important brain regions implicated in schizophrenia, is shown to atrophy at a faster rate in aging. In this study, telomere length (TL) was measured in 30 antipsychotic-naive/free schizophrenia patients and 60 healthy controls using quantitative PCR assay. Hippocampus volume was measured using voxel-based morphometry. Schizophrenia was associated with differential TL between sexes [Status × Sex; F(1,85) = 5.9, p = 0.017, η2 = 0.065]. Male schizophrenia patients had significantly lower relative TL than female patients [F(1,85) = 7.38, p = 0.008], while such sex difference was not observed in healthy controls [F(1,85) = 0.16, p = 0.69]. Schizophrenia patients showed a significant sex-by-telomere interaction with both right & left hippocampus, with male patients showing positive association of telomere length with volume, while female patients showed negative association. Telomere shortening and the positive association of telomere length with hippocampus volume was observed only in male patients with schizophrenia. Since correlational observations in this cross-sectional study does not necessarily support definitive causal relationship, further longitudinal studies examining hippocampus volume and telomere in schizophrenia patients are needed.

High-definition transcranial direct current simulation (HD-tDCS) for persistent auditory hallucinations in schizophrenia

Conventional transcranial Direct Current Stimulation (tDCS) has been reported to alleviate persistent auditory hallucinations (AH) in schizophrenia as an add-on intervention. High-Definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. In this study, add-on HD-tDCS (5 days twice daily session with 2-mA cathodal current on left temporo-parietal junction) using 4 × 1 ring montage significantly reduced persistent AH (t = 3.6;p < 0.01) in schizophrenia patients (N = 19). Add-on HD-tDCS has promising potential to treat persisting AH in schizophrenia. This needs further systematic research.