High-Definition Transcranial Direct Current Stimulation-Primed Intermittent Theta Burst Stimulation in Treatment-Resistant Depression: A Controlled Study.

OBJECTIVES: The aim of this study was to evaluate whether high-definition transcranial direct current stimulation (HDtDCS) priming improves the efficacy of intermittent theta burst stimulation (iTBS) in improving TRD. METHODOLOGY: A prospective hospital-based, randomized control study where the participants were divided into active or sham HDtDCS-primed iTBS stimulation groups for a total of 10 sessions and were assessed on clinical parameters at baseline, end of week 1, and end of week 2 was done. Primary outcome of the study was the difference in Hamilton Depression Rating Scale (HDRS) scores over 2 weeks of HDtDCS-primed iTBS. RESULT: A significant effect of time was seen over HDRS scores in both active and sham groups with a large effect size. Significant effect of time was also found over the Clinical Global Impressions-Severity Scale scores of patients with a large effect size. The difference in the improvement in depressive severity as measured using HDRS and Clinical Global Impressions-Severity Scale scores between active and sham groups was also found to be significant with large effect sizes. CONCLUSION: High-definition tDCS-primed iTBS is superior to normal iTBS in patients with depression who have failed a trial of 2 antidepressants, whereas both mechanisms are of benefit to the patients.

Brain activation alterations with adjunctive deep transcranial magnetic stimulation in obsessive-compulsive disorder: an fMRI study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is one of the most common neuropsychiatric disorders with lifetime prevalence higher than that of schizophrenia and bipolar disorders. Inadequate response to available pharmacological and psychotherapeutic interventions is common in OCD. Adjunctive brain stimulation methods to address the inadequate treatment response in OCD have found a special interest in research. This study aimed to examine the efficacy of adjunctive deep transcranial magnetic stimulation (dTMS) in ameliorating the symptoms of OCD and the effect of dTMS on activation of brain regions while performing the Stroop task using functional magnetic resonance imaging (fMRI). METHODS: A total of 41 patients were assessed for the study out of which 15 OCD patients received 10 sessions of high-frequency dTMS using the H7 coil to target the anterior cingulate cortex and the medial prefrontal cortex over a period of 2 weeks. The Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used for the pre- and post-stimulation clinical assessment. fMRI was used to measure the activation of brain regions while performing the Stroop task. RESULTS: There was a significant improvement in the obsessive-compulsive, anxiety, and depressive symptoms after the 2 weeks of the dTMS treatment. A significant decrease in the activation of left caudate nucleus and adjacent white matter was noted while performing the Stroop task after the dTMS treatment. CONCLUSION: The study provides preliminary evidence for functional correlates of effectiveness of dTMS as an adjunctive treatment modality for OCD.

Psychometric properties and factor structure of the suicidal narrative inventory in major depression: A multicentric evaluation.

BACKGROUND: The Suicidal Narrative Inventory (SNI) is a 38-item self-report measure developed to assess elements of the suicidal narrative, a subacute, predominantly cognitive, presuicidal construct. Our objectives were to assess the factor structure, validity, and reliability of the SNI-38 among adults with major depressive disorder (MDD). METHODS: Using a cross-sectional design, we administered the Hindi version of the SNI along with other self-report measures to adults with MDD, recruited from 24 tertiary care hospitals across India. Confirmatory factor analysis (CFA) was performed to assess the factor structure of SNI-38. Reliability (internal consistency) was assessed using Cronbach's alpha (α). Convergent, discriminant, and criterion validity of the SNI-38 were tested by comparing it against other appropriate measures. RESULTS: We collected usable responses from 654 Hindi-speaking participants (Mean age = 36.9 ± 11.9 years, 50.2% female). The eight-factor solution of the SNI showed good model fit indices (χ2[637] = 3345.58, p <.001, CFI =.98, and RMSEA =.08). Internal consistencies for the SNI subscale scores were good to excellent, α ranging from .73 to.92. While most subscales significantly converged with other measures, associations were comparatively weaker and inconsistent for the 'thwarted belongingness' and 'goal reengagement' subscales. CONCLUSION: Consistent with prior data, our study confirmed an eight-factor solution and demonstrated adequate psychometric properties for the Hindi version of the SNI-38 in our sample. These findings provide empirical support for the use of SNI to assess the suicidal narrative among Indian adults with MDD.

Nerve Growth Factor in Psychiatric Disorders: A Scoping Review.

Background: Neurotrophins have been implicated in multiple psychiatric disorders. Nerve Growth Factor (NGF) is one of the major neurotrophins that has attracted much research interest. Therefore, we undertook, to the best of our knowledge, the first scoping review encompassing all major psychiatric disorders and their relation to NGF. This review aimed to identify the current position of NGF in psychiatric research and to outline present gaps in knowledge, which can be answered with a more detailed systematic review in the future. Methods: Suitable studies were identified using PubMed. A total of 20 studies were included in the review: two on bipolar affective disorder (BPAD), three on schizophrenia, seven on depression, and eight on alcohol use disorder. Results: NGF levels are definitively reduced in BPAD and depression, while NGF levels in schizophrenia decreased further after treatment than in the drug-naïve state. The effect of treatment on NGF levels in depression varied based on treatment modalities and severity of depression. In patients with depression, raised NGF was a predictor of conversion to bipolar disorder (BD). NGF levels were raised in acute alcohol intoxication and withdrawal but normalized slowly as abstinence was maintained. NGF may play a protective role in preventing the toxic ill effect of acute alcohol intoxication on the central nervous system. Conclusion: Based on current knowledge, NGF levels may be a useful biomarker of a chronic mental stress condition. However, further research is needed before it can be used to identify a specific psychiatric illness or predict treatment response.

Clinical efficacy and neurobiological correlates of electroconvulsive therapy in patients with clozapine-resistant/intolerant schizophrenia: study protocol of multi-site parallel arm double-blind randomized sham-controlled study.

Background: A substantial proportion of patients with treatment resistant schizophrenia do not respond well or partially to clozapine, with a subset that does not tolerate an adequate trial of clozapine. Electroconvulsive therapy (ECT) is regarded as one of the augmenting options, but there is a lack of high-quality evidence for this practice. This protocol describes a double-blind randomised sham-controlled modified-ECT trial to evaluate its efficacy in patients with clozapine resistant/intolerant schizophrenia. The study also involves multimodal investigations to identify the response predictors and the mechanistic basis of modified ECT in this population. Methods: One hundred consenting schizophrenia patients with resistance/intolerance to clozapine referred by clinicians for ECT would be randomly assigned to receive true ECT or sham ECT at three study centers. Sham ECT would mimic all the procedures of modified ECT including anaesthesia and muscle relaxation, except the electrical stimulation. After a blinded course, non-responders to sham ECT would be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging [MRI], electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphism) would be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial would evaluate the improvement in positive symptoms (scale for assessment of positive symptoms) of schizophrenia as the primary outcome measure with prediction of this change by resting-state functional-MRI based brain-connectivity as the second primary objective. Registration: Clinical Trial Registry of India (Reg no: CTRI/2021/05/033775) on 24 th May 2021.

Response Processes to Looming Appetitive and Aversive Cues in Euthymic Bipolar Patients and Their First-Degree Relatives: An Exploratory Study.

BACKGROUND: Patients with bipolar disorder demonstrate increased sensitivity to appetitive/rewarding stimuli even during euthymia. On presentation of arousing pictures, they show a peculiar response, suggesting heightened vigilance. While responding to looming arousing cues, studies show subjects with anxiety spectrum disorders exhibit increased reaction time (RT), explained by the "looming-vulnerability model." This study aimed to investigate the responses to looming arousing cues in euthymic bipolar patients and their first-degree relatives, as compared to healthy controls. METHOD: A looming appetitive and aversive cue paradigm was designed for assessing the RT of patients to process appetitive and aversive cues. The behavioral inhibition/activation and sensitivity to reward/punishment amongst the groups were also assessed. RESULTS: The bipolar group showed significantly longer RT to process appetitive cues irrespective of the looming condition. Aversive cues elicited significantly longer RT in both the bipolar group and in first-degree relatives, but only when presented with the looming condition. Significant looming bias was elicited in the bipolar group which suggested a particular cognitive style to looming cues. A composite measure of RT along with sensitivity to reward/punishment distinguishes the bipolar group and their first-degree relatives from the healthy controls. CONCLUSION: The looming vulnerability model may provide important insights for future exploration of cognitive endophenotypes in bipolar disorder.

Evaluation of N-400 Evoked Response Potential in schizophrenia: An endophenotype or a disease marker?

N400 evoked response potentials (ERP) reliably map key semantic deficits in schizophrenia. Assessing them as endophenotypes might help in better understanding of schizophrenia risk and their use as biomarkers. We aimed to study N400 as an endophenotype marker by comparing schizophrenia (SCZ), unaffected first-degree relatives (FDR) and healthy controls (HC) and, by assessing its ability to discriminate these groups. Drug naïve or free SCZ probands (n=30), their unaffected FDRs (n=30) and HC (n=30), underwent a 40-channel ERP recording while performing a custom-made, Hindi- sentence context paradigm task, containing congruent and incongruent conditions. Fifteen centro-parietal (CP) leads, further classified into three regions-midline (CPM), right (CPR) and left (CPL) were selected as electrodes-of-interest for assessing N400. During the incongruent condition, compared to both FDRs and HC, SCZ showed significantly longer N400 latency, at CPM, CPR and CPL, and significantly lesser (more negative) amplitude, at CPM; no significant difference was noted between FDR and HC groups. On discriminant functional analysis, significant N400 predictors could accurately classify 73.3% SCZ from HC and 75% of SCZ from FDR. We conclude that N400 deficits, elicited by the incongruent condition of the sentence task, could be potential biomarkers to define disease state in schizophrenia; they may not be endophenotype markers.

Sources of mu activity and their functional connectivity in perceiving complexities in reciprocal social interactive motion: An exploratory study using the 'Namaste' task.

Cognitive processes underlying reciprocal social interactions are understood by the mechanism of embodiment, which is closely related to the mirror neuron system. Electroencephalographic (EEG) mu activity is a neural marker of the mirror neuron system. This study investigated the mu activity, localization of its sources and functional connectivity, which was induced while watching reciprocal social interactive motion across various degrees of complexity. Eighteen healthy participants underwent high-resolution EEG recording using 256-channels while they watched a specifically designed, culture specific, video task that showed two persons interacting socially using body gestures. Task complexity was determined by (1) whether there was an identical gestural response or a non-identical one; (2) whether the participant watched two persons interacting or was virtually involved in the interaction. Source localization and functional connectivity analysis was conducted for mu activity across various tasks. We also correlated mu activity and functional connectivity measures with serum BDNF. We found that spectral densities in various brain sources of mu activity and their increased functional connectivity distinguished identical and non-identical reciprocal expression observations, while mu suppression alone did not discriminate various degrees of complexities. These findings might have important implications in the understanding of mechanisms underlying mirror neuron dysfunction in various psychiatric disorders.

Resting state theta band source distribution and functional connectivity in remitted schizophrenia.

Increased resting theta activity is one consistent observation occurring during all the phases of schizophrenia. However, the resting theta oscillations during the remission phase are yet unclear. We studied resting theta current source density and functional connectivity in remitted schizophrenia and compared with healthy controls. Significantly increased current source density was found in the dominant anterior cingulate cortex. Increased connectivity between the inferior parietal lobe bilaterally and between the left inferior parietal lobe and right middle frontal gyrus was also found. It may be concluded that schizophrenia patients have aberrant regional theta band current source density and functional connectivity even during remission.