Aditi Subramaniam

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.

Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naïve schizophrenia: evidence for differential susceptibility?

Background Various lines of evidence including epidemiological, genetic and foetal pathogenetic models suggest a compelling role for Interleukin-6 (IL-6) in the pathogenesis of schizophrenia. IL-6 mediated inflammatory response triggered by maternal infection or stress induces disruption of prenatal hippocampal development which might contribute towards psychopathology during adulthood. There is a substantial lack of knowledge on how genetic predisposition to elevated IL-6 expression effects hippocampal structure in schizophrenia patients. In this first-time study, we evaluated the relationship between functional polymorphism rs1800795 of IL-6 and hippocampal gray matter volume in antipsychotic-naïve schizophrenia patients in comparison with healthy controls. Methodology We examined antipsychotic-naïve schizophrenia patients [N = 28] in comparison with healthy controls [N = 37] group matched on age, sex and handedness. Using 3 Tesla – MRI, bilateral hippocampi were manually segmented by blinded raters with good inter-rater reliability using a valid method. Additionally, Voxel-based Morphometry (VBM) analysis was performed using hippocampal mask. The IL-6 level was measured in blood plasma using ELISA technique. SNP rs1800795 was genotyped using PCR and DNA sequencing. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms. Results Schizophrenia patients had significantly deficient left and right hippocampal volumes after controlling for the potential confounding effects of age, sex and total brain volume. Plasma IL-6 levels were significantly higher in patients than controls. There was a significant diagnosis by rs1800795 genotype interaction involving both right and left hippocampal volumes. Interestingly, this effect was significant only in men but not in women. Conclusion Our first time observations suggest a significant relationship between IL-6 rs1800795 and reduced hippocampal volume in antipsychotic-naïve schizophrenia. Moreover, this relationship was antithetical in healthy controls and this effect was observed in men but not in women. Together, these observations support a “differential susceptibility” effect of rs1800795 in schizophrenia pathogenesis mediated through hippocampal volume deficit that is of possible neurodevelopmental origin.

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.

Monotherapy with tDCS for Schizophrenia: a case report.

positive response to cTBSmight have been related to the association of risperidonewith cTBS orwas primed bya course of low frequency rTMS completed a month before. However, the fact that this patient who suffered fromchronic persistentAVH responded to cTBSbut not to rTMS in addition to the fact that the improvements in her AHRS scores persisted with maintenance cTBS suggest that observed clinical changes were an effect of stimulation by cTBS. The encouraging findings of this case safely treated in a private practice setting aswell as those of the three previously published cases [8,9,10] should be further investigated and confirmed in sufficiently powered placebo-controlled, double-blind studies.

Neural basis of tDCS effects on auditory verbal hallucinations in schizophrenia: a case report evidence for cortical neuroplasticity modulation.

Transcranial direct current stimulation (tDCS) has been reported to ameliorate auditory hallucinations that are nonresponsive/minimally responsive to antipsychotic treatment in schizophrenia. The neurobiological basis of the tDCS effects in ameliorating auditory hallucinations is yet to be explored. In this case report, for the first time, using the novel method for noninvasive assessment of cortical plasticity, we demonstrate potential neuroplasticity effect of tDCS in improving treatment-resistant auditory hallucinations in a schizophrenic patient.

Rapid improvement of auditory verbal hallucinations in schizophrenia after add-on treatment with transcranial direct-current stimulation.

Abstract Treatment of nonresponsive auditory hallucinations in schizophrenia have been reported to improve with transcranial direct-current stimulation. This case description illustrates the use of add-on transcranial direct-current stimulation for rapid amelioration of auditory hallucinations in schizophrenia during the acute phase. Because transcranial direct-current stimulation is safe, largely well tolerated, and relatively inexpensive, this add-on treatment option is worth exploring through further rigorous studies.

Clinical correlates of hippocampus volume and shape in antipsychotic-naïve schizophrenia

While volume deficit of hippocampus is an established finding in schizophrenia, very few studies have examined large sample of patients without the confounding effect of antipsychotic treatment. Concurrent evaluation of hippocampus shape will offer additional information on the hippocampal aberrations in schizophrenia. In this study, we analyzed the volume and shape of hippocampus in antipsychotic-naïve schizophrenia patients (N=71) in comparison to healthy controls (N=82). Using 3-T MRI data, gray matter (GM) volume (anterior and posterior sub-divisions) and shape of the hippocampus were analyzed. Schizophrenia patients had significant hippocampal GM volume deficits (specifically the anterior sub-division) in comparison to healthy controls. There were significant positive correlations between anterior hippocampus volume and psychopathology scores of positive syndrome. Shape analyses revealed significant inward deformation of bilateral hippocampal surface in patients. In conclusion, our study findings add robust support for volume deficit in hippocampus in antipsychotic-naïve schizophrenia. Hippocampal shape deficits in schizophrenia observed in this study map to anterior CA1 sub-region. The differential relationship of anterior hippocampus (but not posterior hippocampus) with clinical symptoms is in tune with the findings in animal models. Further systematic studies are needed to evaluate the relationship between these hippocampal gray matter deficits with white matter and functional connectivity to facilitate understanding the hippocampal network abnormalities in schizophrenia.

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.

Clinical correlates of saccadic eye movement in antipsychotic-naïve schizophrenia

Some aspects of saccadic performance have been found to be abnormal in chronic schizophrenia. The majority of this research has, however, been performed on patients treated with long-term antipsychotic medication. Very few studies have examined saccadic performance in antipsychotic-naïve/free patients. There are also very few studies describing the relationship between saccadic performance and clinical symptoms, particularly in antipsychotic free patients. In this study, we compared pro and antisaccade performance in a large sample of antipsychotic-naïve/free schizophrenia patients (N = 45) with healthy controls (N = 57). Clinical symptoms were assessed using Scale for Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS). In the antisaccade task, patients made significantly more errors, and their correct antisaccades had smaller amplitudes in comparison to healthy controls. Higher error rates were associated with increased severity of hallucinations. In the prosaccade task, patients had less accurate final eye positions, and made saccades with slower latency and reduced amplitude compared to the healthy controls. These observations in schizophrenia patients without the potential confounds of antipsychotic treatment suggest intrinsic link between saccadic deficits and schizophrenia pathogenesis. The relationship between antisaccade errors and hallucination severity supports the potential link between hallucinations and deficits in inhibitory control.