Home-based tDCS for schizophrenia: Exploring the feasibility of a standard operating procedure.

Transcranial Direct Current Stimulation (tDCS), a safe and easy-to-administer noninvasive brain stimulation technique, holds promise in managing auditory verbal hallucinations (AVH) in schizophrenia. However, its short-lasting effect often leads to frequent hospital visits for booster/maintenance sessions, posing logistical challenges. Home-based tDCS offers a potential solution that improves accessibility; however, careful standardisation is required to ensure safe and effective application. We present a case of schizophrenia, where add-on home-based tDCS was administered based on a standard operating procedure (SOP) developed to address challenges unique to home administration, like device-related factors, patient and caregiver-related factors, and comprehensive caregiver training protocol. As a part of training, caregivers underwent observational learning, mannequin-based training for electrode placement, and assisted live-patient sessions. Pre and post-training competency assessments were done to ensure proficiency and safe administration. Over ten days, home-based tDCS sustained improvements in AVH without adverse effects. This case report supports the feasibility of home-based tDCS and provides a detailed SOP for implementing a safe and effective home-based tDCS treatment regime. This comprehensive SOP with a training protocol is notedly efficient for enhancing the accessibility and affordability of tDCS treatment protocols.

Repetition-Dependent Adaptation and Prediction Error Signalling in Schizophrenia Patients With Auditory Hallucinations: A Roving Mismatch Negativity Study.

BACKGROUND: Dysregulated prediction error-signalling may explain auditory hallucinations in schizophrenia (SZ-AH). Roving mismatch negativity (rMMN) is an event-related potential (ERP) index where the deviant tone becomes the new standard with repetitions. Longer repetitions of standard stimuli yield a more positive sensory-adaptation response (Repetition Positivity-RP), elicit a stronger deviance-detection when interrupted (deviant negativity-DN), and the difference waveform between them reflects the strength of prediction-error signalling (mismatch negativity-MMN). METHODS: Twenty-three SZ-AH patients and twenty-three healthy controls (HC) underwent rMMN assessment. Various standard stimuli were repeated in sets of 3, 8 and 33 yielding three components for RP (RP3, RP8, RP33), DN (DN3, DN8, DN33), and MMN (MMN3, MMN8, MMN33). Amplitudes and latencies were compared across groups. Correlation between (a) rMMN amplitudes and latencies, and clinical variables in SZ-AH, and (b) the RP-DN amplitude pair for all three repetition sets (3, 8, 33) were also examined. RESULTS: All DN and MMN33 amplitudes were significantly suppressed in SZ-AH, while RP amplitudes were not. MMN33 latency was significantly longer in SZ-AH than HC. A few amplitudes and latencies significantly correlated with the frequency of AH. HC showed a significant positive correlation between RP-DN amplitude pairs for sets of 3 and 8 but not for 33; SZ-AH group's correlation profile was opposite to this. DISCUSSION: The link between repetition-dependent sensory-adaptation and deviance-detection is perturbed in SZ-AH. The unimpaired RP profile in SZ-AH is due to potential interference of AH with auditory information processing, and does not indicate a preserved short-term plasticity of the echoic memory trace.

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I.

BACKGROUND: Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. AIM OF THE STUDY: This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. METHODS: NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM (n = 31), HR (n = 31), and HC (n = 30) subjects, matched for age (years) (p = 0.44) and sex (p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. RESULTS: Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). CONCLUSIONS: AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD.

Eye movement abnormalities and Atypical Neurodevelopmental markers as Composite Measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder.

Neurohemodynamic correlates of BDNF gene expression in schizophrenia patients with working memory deficits: A functional MRI study.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD. METHODS: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis. RESULTS: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively. CONCLUSION: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.

Functional near-infrared spectroscopy in schizophrenia patients with auditory verbal hallucinations: Preliminary observations.

Auditory Signal Detection (ASD) theory postulates that auditory verbal hallucinations (AVH) result from an aberrant association of meaningful connection to abstract noises. In this study, schizophrenia (SZ) patients with persistent AVH (N = 17) and matched controls (N = 25) performed an ASD task with concurrent functional near-infrared spectroscopy recording targetting the left dorsolateral prefrontal cortex (L-DLPFC) and left temporoparietal junction (L-TPJ). During the task, discriminability index had a significant negative correlation, and early deoxyhemoglobin (HbR) latency at L-TPJ positively correlated with AVH scores. Also, patients had significantly lower discriminability, early HbR latency at L-TPJ, and delayed latency at L-DLPFC. This finding suggests the presence of ASD abnormalities and impaired auditory processing in SZ patients with AVH supporting ASD-based pathogenesis.

Effect of transcranial direct current stimulation on in-vivo assessed neuro-metabolites through magnetic resonance spectroscopy: a systematic review.

OBJECTIVES: Previous studies have examined the effect of transcranial direct current stimulation (tDCS) on the in-vivo concentrations of neuro-metabolites assessed through magnetic resonance spectroscopy (MRS) in neurological and psychiatry disorders. This review aims to systematically evaluate the data on the effect of tDCS on MRS findings and thereby attempt to understand the potential mechanism of tDCS on neuro-metabolites. METHODS: The relevant literature was obtained through PubMed and cross-reference (search till June 2020). Thirty-four studies were reviewed, of which 22 reported results from healthy controls and 12 were from patients with neurological and psychiatric disorders. RESULTS: The evidence converges to highlight that tDCS modulates the neuro-metabolite levels at the site of stimulation, which, in turn, translates into alterations in the behavioural outcome. It also shows that the baseline level of these neuro-metabolites can, to a certain extent, predict the outcome after tDCS. However, even though tDCS has shown promising effects in alleviating symptoms of various psychiatric disorders, there are limited studies that have reported the effect of tDCS on neuro-metabolite levels. CONCLUSIONS: There is a compelling need for more systematic studies examining patients with psychiatric/neurological disorders with larger samples and harmonised tDCS protocols. More studies will potentially help us to understand the tDCS mechanism of action pertinent to neuro-metabolite levels modulation. Further, studies should be conducted in psychiatric patients to understand the neurological changes in this population and potentially unravel the neuro-metabolite × tDCS interaction effect that can be translated into individualised treatment.

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder-A large case series.

OBJECTIVE: The present study is a large case series evaluating the benefits of transcranial direct current stimulation (tDCS) in treatment-resistant obsessive compulsive disorder (OCD). METHODS: We reviewed the charts of 32 patients with treatment-resistant OCD who received 10-20 sessions of anodal pre-SMA tDCS. RESULTS: Overall, 9 (28 %) showed at least partial response to tDCS at the end of 10-20 sessions [responders = 8 (25 %), partial responders = 1 (3%)]. Two out of three partial responders at the end of 10 sessions had response at the end of 20 sessions. CONCLUSIONS: tDCS may benefit a proportion of patients with treatment-resistant OCD.

fNIRS study of prefrontal activation during emotion recognition-A Potential endophenotype for bipolar I disorder?

BACKGROUND: Facial emotion recognition (FER) deficit is documented in many psychiatric disorders, including bipolar disorder (BD). However, its role as a risk-marker in BD is not well researched. In the present study, we investigated the role of FER and the corresponding prefrontal neurohemodynamic changes (PNHC) with functional near infra-red spectroscopy (fNIRS) in patients with BD and subjects at high risk for BD compared to healthy subject. METHODS: Using a cross-sectional case-control design we compared 14 patients with first episode mania (FEM) in remission (BD group), 14 healthy siblings of BD patients (HR group), and 13 matched healthy subjects (HC group). FER was assessed using a computer-based task called Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS). Simultaneously, the corresponding PNHC was recorded with fNIRS. Kruskal Wallis H test was used to analyze between-group differences and Spearman's rho for correlation analysis. RESULTS: The three groups were comparable on socio-demographics (all p>0.09) except education (p = 0.03). HR group had the most hyper-activation in the bilateral DLPFC during the TRENDS task (all p<0.05). There was no significant between-group differences in the FER performance and no significant correlation between the FER performance and the PNHC in the HR and BD groups (all p>0.35). LIMITATIONS: The potential confounding effect of medications in the BD group. CONCLUSIONS: The hyper-activation of the DLPCF in HR group during FER could indicate an increased risk for BD. However, the lack of similar findings in the BD group might reflect a possible normalizing effect of medications. It is equally likely that differences in the PNHC are detectable earlier than the differences in FER task performance during the course of the illness. This requires further exploration.

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS).

INTRODUCTION: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients. METHODS: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS. RESULTS: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients. CONCLUSION: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.

Prefrontal cortex activation during working memory task in schizophrenia: A fNIRS study.

Neurocognitive cognitive deficits including working memory (WM) impairment is a key component of schizophrenia (SCZ). Though a prefrontal cortex (PFC) abnormality is recognised to contribute to WM impairment, the exact nature of its neurobiological basis in SCZ is not well established. Functional near infra-red spectroscopy (fNIRS) is an emerging low-cost neuroimaging tool to study neuro-hemodynamics. In this background, we examined the hemodynamic activity during a WM task in schizophrenia using fNIRS. fNIRS was acquired during computerised N-back (zero-, one- & two-back) task in 15 SCZ patients and compared with 22 healthy controls. Performance in N-back test were calculated using signal detection theory alongside the mean reaction times. Concentration and latencies of oxy-, deoxy-, and totalhaemoglobin, and oxygen saturation were computed from 8*8 optodes positioned over bilateral PFC. SCZ performed poorly as measured by most of the WM parameters (p < 0.05). Lesser deoxyhemoglobin concentration (two > zero, at right BA10, p = 0.006) was noted in the right frontopolar cortex in SCZ surviving multiple-comparison correction. In addition, olanzapine equivalent doses correlated negatively with right frontopolar cortex activation (two > zero back, BA10, ρ = 0.70, p = 0.004) and better performance in two back (false alarm rate, ρ = 0.61, p = 0.015). A delayed but compensatory hyperactivation of right frontopolar cortex noted in SCZ may underlie the WM deficit in SCZ. Future studies are recommended to replicate the role of right frontopolar cortex in WM using larger samples and systematically explore the effect of antipsychotics on them.

Impact of NRG1 HapICE gene variants on digit ratio and dermatoglyphic measures in schizophrenia.

Multiple lines of evidence have suggested a potential role of Neuregulin-1 (NRG1) in the neurodevelopmental pathogenesis of schizophrenia. Interaction between genetic risk variants present within NRG1 locus and non-specific gestational putative insults can significantly impair crucial processes of brain development. Such genetic effects can be analyzed through the assessment of digit ratio and dermatoglyphic patterns. We examined the role of two well-replicated polymorphisms of NRG1 (SNP8NRG221533 and SNP8NRG243177) on schizophrenia risk and its probable impact on the digit ratio and dermatoglyphic measures in patients (N = 221) and healthy controls (N = 200). In schizophrenia patients, but not in healthy controls, a significant association between NRG1 SNP8NRG221533 C/C genotype with lower left 2D:4D ratio, as well as with higher FA_TbcRC and DA_TbcRC. The substantial effect of SNP8NRG221533 on both digit ratio and dermatoglyphic measures suggest a potential role for NRG1 gene variants on neurodevelopmental pathogenesis of schizophrenia.

Working memory performance with online-tDCS in schizophrenia: A randomized, double-blinded, sham-controlled, partial cross-over proof-of-concept study.

Combining cognitive retraining with transcranial direct current stimulation (tDCS) has been hypothesized to improve cognitive deficits in schizophrenia. The effect of combining a neuropsychological/psychophysiological task with tDCS, called "online-tDCS" for cognitive enhancement in schizophrenia is not rigorously assessed. In this proof-of-concept study, we aimed at evaluating the effect of a single session online-tDCS on working memory(WM) and its transferability to other cognitive functions. Numerical n-back(NNB), digit symbol substitution test(DSST), emotional matching and labelling test(E-MALT), and anti-saccade eye movement beeforefore and after 20 min tDCS (anode: left dorsolateral prefrontal cortex and cathode: left temporoparietal junction) applied during Sternberg's task(WM-task) were assessed. Twenty-three schizophrenia patients with cognitive deficits were randomized to receive either online-tDCS or offline-tDCS (without simultaneous Sternberg's task) sessions. All patients received one session each of active and sham tDCS in a randomized counterbalanced double-blind cross-over design. RMANOVA revealed a significant interaction effect between tDCS type (Online/Offline) x activeness (active/sham) of tDCS; the reaction time during 2-back performance in the NNB test improved in online-sham (F = 5.23, p < 0.038) but not online-active tDCS session. No significant changes were noted in DSST, E-MALT, and anti-saccade performance. Improved performance after online-sham tDCS suggests that performing the Sternberg's task enhanced 2-back performance. The counterintuitive observation was noted with respect to the non-enhancement of WM performance on combining the task to tDCS. Aberrant plasticity in schizophrenia might attain a transitional ceiling that would have resulted in restriction of enhancement on combining the two plasticity modulators. The transferability of improvement to other cognitive domains could not be ascertained.

Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions.

Transcranial direct current stimulation (tDCS), a non-invasive, neuromodulatory technique, is being increasingly applied to several psychiatric disorders. In this study, we describe the side-effect profile of repeated tDCS sessions (N = 2005) that were administered to 171 patients (156 adults and 15 adolescents) with different psychiatric disorders [schizophrenia [N = 109], obsessive-compulsive disorder [N = 28], alcohol dependence syndrome [N = 13], mild cognitive impairment [N = 10], depression [N = 6], dementia [N = 2] and other disorders [N = 3]]. tDCS was administered at a constant current strength of 2 mA with additional ramp-up and ramp-down phase of 20 s each at the beginning and end of the session, respectively. Other tDCS protocol parameters were: schizophrenia and obsessive-compulsive disorder: 5-days of twice-daily 20-min sessions with an inter-session interval of 3-h; Mild cognitive impairment/dementia and alcohol dependence syndrome: at least 5-days of once-daily 20-min session; Depression: 10-days of once-daily 30 min session. At the end of each tDCS session, any adverse event observed by the administrator and/or reported by the patient was systematically assessed using a comprehensive questionnaire. The commonly reported adverse events during tDCS included burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%). Most of the adverse events were noted to be mild, transient and well-tolerated. In summary, our observations suggest that tDCS is a safe mode for therapeutic non-invasive neuromodulation in psychiatric disorders in adults as well as the adolescent population.

Eye movement tracking in pediatric obsessive compulsive disorder.

Till date researchers have elucidated the neurobiological substrates in OCD using methods like neuroimaging. However, a potential biomarker is still elusive. The present study is an attempt to identify a potential biomarker in pediatric OCD using eye tracking. The present study measured pro-saccade and anti-saccade parameters in 36 cases of pediatric OCD and 31 healthy controls. There was no significant difference between cases and controls in the error rate, peak velocity, position gain and latency measures in both pro-saccade and anti-saccade eye tracking tasks. With age, anti-saccades become slower in velocity, faster in response and more accurate irrespective of disorder status of the child. Pro-saccades also show a similar effect that is less prominent than anti-saccades. Gain measures more significantly vary with age in children with OCD than the controls, whereas latency measures positively correlated with age in children with OCD as opposed to being negatively correlated in the controls. Findings of this study do not support any of the eye tracking measures as putative diagnostic bio-markers in OCD. However, latency and gain parameters across different age groups in anti-saccade tasks need to be explored in future studies.

Add-on HD-tDCS for obsessive-compulsive disorder with comorbid bipolar affective disorder: A case series.

Obsessive-compulsive disorder (OCD) with comorbid bipolar affective disorder (BPAD) is often faced with a therapeutic challenge. Pharmacological treatment strategy engaged towards alleviating symptoms in OCD has the propensity to precipitate a manic switch in patients with comorbid BPAD. Advanced non-invasive brain stimulation techniques like high definition transcranial direct current stimulation (HD-tDCS) may target the symptoms of OCD while preventing a probable manic switch in a vulnerable population. In this case series, we targeted OC symptoms in three patients by giving 2 mA of anodal HD-tDCS at their pre-SMA (localized using 10/10 EEG system) with 4 surrounding return electrodes of opposite polarity for 20 min of two sessions having an intersession gap of 20 min receiving a maximum of 20 sessions. We found that the patients showed significant improvement (more than 25%) in their OC symptoms while having no affective side effects and this effect was replicated in one of the two patients in repeating the treatment for relapse. This case series highlights the efficacy and durability of the effect of HD-tDCS as an add-on treatment modality in three patients who were treated for OC symptoms in the context of a comorbid bipolar disorder, two of them receiving repeat courses on relapse.

Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: A randomized, double blinded, sham controlled trial.

BACKGROUND: A significant proportion of obsessive compulsive disorder (OCD) patients do not respond to specific serotonin reuptake inhibitors (SSRIs). There is a need to evaluate novel treatment options for OCD. OBJECTIVE: In this double blinded, randomized, sham controlled study, we investigated the efficacy of add-on transcranial direct current stimulation (tDCS) in reducing the symptoms in SSRI-resistant OCD patients by employing anodal pre-supplementary motor area (pre-SMA) stimulation. METHOD: Twenty-five patients with DSM-IV OCD having persistent symptoms despite adequate and stable treatment with at least one SSRI were randomly allocated to receive 20 min of verum (active) 2-mA tDCS or sham stimulation twice daily on 5 consecutive days [anode over Pre-SMA; cathode over right supra-orbital area]. Response to treatment was defined as at least 35% reduction in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score along with a Clinical Global Impression - Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). RESULTS: The response rate was significantly greater in the verum tDCS(4 out of 12) compared to sham-tDCS (0 out of 13) [Fisher's exact test, p = 0.04]. Repeated measures analysis of variance with tDCS type (verum vs. sham) as between subjects factor showed that there was a significant tDCS-type X time-point interaction with significantly greater reduction of YBOCS total score [F (1,22) = 4.95,p = 0.04,partial-η2 = 0.18] in verum-tDCS group. CONCLUSIONS: The results of this RCT suggest that tDCS may be effective in treating SSRI-resistant OCD. Future studies should examine the efficacy in larger samples of OCD and explore other potential target regions using randomized sham-controlled designs, in addition to examining the sustainability of the beneficial effects. TRIAL REGISTRATION: Clinical Trials Registry India (http://ctri.nic.in/Clinicaltrials/login.php): Registration Number- CTRI/2016/04/006837).

A Functional Domain Based Approach in Neurocognitive Rehabilitation with Transcranial Direct Current Stimulation: A Case Report.

Transcranial direct current stimulation (tDCS) is a novel brain stimulation technique which has kindled hope in alleviating motor, language as well as cognitive deficits in neuronal injury. Current case report describes application of tDCS in two phases using two different protocols in a patient with hypoxic injury. In the first phase anodal stimulation of dorsolateral prefrontal cortex improved the language fluency. Subsequently, after 6 months second phase application of anodal stimulation over posterior parietal region targeted arithmetic and working memory deficits. Individualising the treatment protocols of brain stimulation, based on the lesion and the functional deficits, for neuro-rehabilitation is emphasised.

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.