Obsessive compulsive disorder (OCD) is a common psychiatric illness and significant research has been ongoing to understand its neurobiological basis. Neuroimaging studies right from the 1980s have ...revealed significant differences between OCD patients and healthy controls. Initial imaging findings showing hyperactivity in the prefrontal cortex (mainly orbitofrontal cortex), anterior cingulate cortex and caudate nucleus led to the postulation of the cortico-striato-thalamo-cortical (CSTC) model for the neurobiology of OCD. However, in the last two decades emerging evidence suggests the involvement of widespread associative networks, including regions of the parietal cortex, limbic areas (including amygdala) and cerebellum. This narrative review discusses findings from structural Magnetic Resonance Imaging (MRI), Diffusion Tensor Imaging(DTI), functional (functional MRI (fMRI), Single photon emission computed tomography (SPECT), Positron emission tomography (PET), functional near-infrared spectroscopy (fNIRS), combined structural and functional imaging studies and meta-analyses. Subsequently, we collate these findings to describe the neurobiology of OCD including CSTC circuit, limbic system, parietal cortex, cerebellum, default mode network and salience network. In future, neuroimaging may emerge as a valuable tool for personalised medicine in OCD treatment.
Proven treatment strategies for obsessive- compulsive disorder (OCD) include pharmacotherapy with serotonin reuptake inhibitors and cognitive behavior therapy (CBT). A significant proportion of ...patients (25%-30%) fail to respond to these treatment options, necessitating the need for additional treatment options to improve treatment outcomes and quality of life in patients with OCD. Augmentation strategies using various glutamatergic agents have been explored, with diverse outcomes. The aim of this review is to give an overview of the glutamatergic system in the brain with a focus on glutamatergic abnormalities in OCD and to review the existing evidence for various glutamatergic agents used for augmentation.
Aim
Immunopathogenesis remains a widely appreciated etiopathological model of schizophrenia. Persistent efforts have aimed to identify schizophrenia biomarkers indexing immune system abnormalities ...and also immuno‐dampening effects of antipsychotic medications. Although data arising from published reports are encouraging, such studies are limited to a few immune parameters and not focused on a specific pathway. Th17 cells‐mediated immuno‐inflammatory responses have emerged as a potential mechanism in various neuropsychiatric conditions, including schizophrenia. The Th17 pathway is distinctly regulated through a coordinated action of multiple cytokines and transcription factors. In this study, we explored whether antipsychotic medication has any effect on the cytokines and transcription factors of the Th17 pathway.
Methods
A total of 27 drug‐naive schizophrenia patients were recruited and followed up for 3 months after initiation of antipsychotic medication. Lymphocyte gene expression levels of two transcription factors (STAT3 and RORC) and one of their upstream regulators, IL6, were quantified before and after treatment. Plasma levels of cytokines, such as interleukin (IL)‐1β, IL‐6, IL‐17A, IL‐23, and IL‐33, were also analyzed before and after treatment.
Results
Treatment with antipsychotic medication for 3 months resulted in significant downregulation of STAT3 gene expression as well as reduction in plasma levels of IL‐1β, IL‐6, and IL‐17A. Significant reduction in total scores for the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms was also observed in schizophrenia patients after 3 months of antipsychotic treatment.
Conclusion
Our findings suggest possible immuno‐modulatory effects of antipsychotic medication on the critical regulators, such as IL‐6 and STAT3, of the Th17 pathway in schizophrenia patients. The IL‐6/STAT3 signaling axis involved in the transcriptional regulation of Th17 cells might appear as an important target of antipsychotic treatment in schizophrenia patients. Alternatively, irrespective of the effect of antipsychotic drugs, the IL‐6/STAT3 signaling axis might be crucially involved in ameliorating psychotic symptoms.
Obsessive-compulsive disorder (OCD) is a complex neuropsychiatric disorder with a chronic course, contributing to significant socio-occupational dysfunction. Forty percent of patients remain ...treatment refractive despite mainstream treatment options such as serotonin-reuptake inhibitors and cognitive behavior therapy. Noninvasive brain stimulation approaches such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have piqued interest as add-on treatment options in OCD. This review focuses on summarizing the TMS and tDCS studies in OCD with respect to their study design and stimulation parameters and key findings. We also briefly discuss the limitations and future directions noninvasive brain stimulation in OCD.
Mismatch negativity (MMN) amplitude is attenuated in schizophrenia patients (SZ). However, variability in illness course among SZ samples and types of deviant stimuli used in MMN paradigms have ...contributed to inconsistent findings across studies. Though MMN is suggested to be impaired in schizotypy, the potential link between the two is yet to be systematically examined in unaffected first-degree relatives of schizophrenia patients (FDR).
The SZ sample had twenty-two drug-naïve or drug-free patients (dSZ) and thirty chronic/medicated patients (cSZ). dSZ and cSZ patients were compared with thirty-six unaffected FDR and thirty-two healthy controls (HC) using a two-tone passive auditory oddball MMN paradigm in an event-related potential experiment with two conditions (presented as separate blocks)–duration-deviant (duration-MMN) and frequency-deviant (frequency-MMN). Schizotypy scores and MMN indices were examined for correlation in FDR.
Duration-MMN amplitude was significantly attenuated in both dSZ and cSZ compared to other groups. dSZ and cSZ did not differ on MMN indices. Psychopathology scores and features of illness (illness duration, medication dosage, etc.) did not correlate with MMN indices. In FDR, Schizotypal trait measures did not correlate with MMN indices.
Duration-MMN emerged as a more robust indicator of prediction error signalling deficit in SZ. Frequency-MMN amplitude did not significantly differ among the groups, and MMN indices did not correlate with state and trait measures of schizophrenia-related psychopathology. These findings reiterates that auditory sensory processing captured by MMN is likely reflective of dynamic cognitive functions at the point of testing, and is unlikely to be an expression of enduring symptomatology.
•Duration-MMN amplitude is attenuated in chronic/medicated (cSZ) and drug-naïve/free (dSZ) schizophrenia patients in comparison to FDR and HC.•Frequency-deviant mismatch negativity (frequency-MMN) amplitude did not significantly differ between the groups.•Duration-MMN and frequency-MMN indices did not significantly differ between medicated/chronic SZ patients and drug-naïve or drug-free/early-course SZ patients.
•Effects with tDCS are likely to act through synaptic plasticity and site of dendritic activation by neurochemical and vascular mechanisms.•For targeted effect with HD-tDCS, there is scope for ...experimentation with different stimulation parameters and montage configurations.•There are evidences for significant modulation of cognitive functions in healthy volunteers with HD-tDCS in controlled trials.•In patients as noted in naturalistic studies, most commonly targeted conditions using HD-tDCS are aphasia and auditory hallucinations.
HD-tDCS (High-definition transcranial direct current stimulation) is a novel non-invasive brain stimulation (NIBS) technique based on the principle that when weak intensity electric currents are targeted on specific areas of the scalp, they cause underlying cortical stimulation. HD-tDCS shares its technical methodology with conventional tDCS (montage comprising of one anode and one cathode) except for a few modifications that are believed to have focal and longer-lasting neuromodulation effects. Although HD-tDCS is a recently available NIBS technique, impactful studies, case reports, and few controlled trials have been conducted in this context, facilitating an understanding of its neurobiological effects and the clinical translation of the same in health care set-up. The current article narratively reviews the mechanism of action of HD-tDCS, and it systematically examines the cognitive, clinical, and neurobiological effects of HD-tDCS in healthy volunteers as well as patients with neuropsychiatric conditions. Thus, this review attempts to explore the role of HD-tDCS in present-day practice and the future in the context of various neurological and psychiatric disorders.
Persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications are reported in about 20–30% of schizophrenia patients. Transcranial Direct Current Stimulation ...(tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), we sought to examine the effect of add-on tDCS anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days to treat refractory AVH in schizophrenia patients (N=25); following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type verum (N=12) vs. sham (N=13) as between subjects factor demonstrated a significant tDCS-type X time-point interaction F=21.5, p<0.001, partial-η2=0.48 with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia.
Glutamate is a ubiquitous excitatory neurotransmitter, which is involved in normal physiology, a variety of central nervous system (CNS) functions, including excitotoxicity and neuronal migration. It ...is implicated in the pathogenesis of various neuropsychiatric disorders including epilepsy, Parkinson's disease, Alzheimer's dementia, schizophrenia and obsessive compulsive disorder (OCD). Over the years, a growing body of evidence has helped researchers understand the mechanisms underlying glutamatergic involvement in the pathogenesis of these disorders. In this review, we attempt to elucidate the role of glutamate in OCD, which is a chronic psychiatric condition with significant morbidity. This article provides current perspectives on the role played by glutamate in the pathogenesis, clinical symptoms and treatment response in OCD, a critical analysis of existing and emerging evidence, both clinical and preclinical, followed by a summary and future directions.
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