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.

Paroxysmal dystonia and psychotic exacerbations in chronic psychosis: Diagnostic dilemmas and preliminary treatment approaches.

Patients with chronic psychosis on prolonged antipsychotic therapy may present with paroxysmal dystonia along with an exacerbation of their psychotic symptoms: paroxysmal dystonia and psychotic exacerbations (PDPE). The interindividual variability in the clinical presentations of PDPE can pose challenges in its diagnosis and treatment. The objectives of this work are to (i) discuss this rare phenomenon through a series of 10 patients and a relevant literature review, (ii) conceptualize its neurobiological underpinnings, and (iii) explore the preliminary treatment approaches for its management. Acute stress and/or a dysfunctional gamma-aminobutyric acid (GABA) ergic or dopaminergic system may be implicated in the pathogenesis of PDPE. The episodes respond acutely to parenteral benzodiazepines, while long-term management can be achieved by reducing antipsychotic doses, switching to clozapine or using central GABA enhancers. This article is the first attempt at conceptualizing and exploring treatment options for the rare condition PDPE and intends to guide future research in this regard.

Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses.

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study. METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder (n = 61), obsessive-compulsive disorder (n = 58), schizophrenia (n = 52), substance dependence (n = 59) or co-occurring diagnoses (n = 38), while 241 were at-risk first-degree relatives who were either unaffected (n = 210) or had other depressive or anxiety disorders (n = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated. RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder. CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

Online Theta Frequency Transcranial Alternating Current Stimulation for Cognitive Remediation in Schizophrenia: A Case Report and Review of Literature.

Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that uses low-intensity alternating current, has been postulated to be a potential therapeutic option in treating the cognitive deficits in schizophrenia. Transcranial alternating current stimulation synchronizes the neural oscillations to the applied stimulation frequency in the stimulated cortical regions. In this report, we have reviewed the literature pertinent to the clinical application of tACS in psychiatric disorders; in addition, we have described the clinical use of online theta tACS in a schizophrenia patient with cognitive deficits. Online theta tACS led to improvement in working memory, attention, processing speed, and emotional processing. The beneficial effect of tACS persisted during reassessment of the patient after 50 days. Transcranial alternating current stimulation, given its noninvasiveness, safety, and ease of administration, has the potential to ameliorate cognitive deficits in neuropsychiatric disorders like schizophrenia.

Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia.

OBJECTIVE: Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia. METHODS: Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20). RESULTS: The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18]. CONCLUSION: COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Standards for medical devices: Electroconvulsive therapy machine.

The manuscript calls for establishing a standard for electroconvulsive devices by manufacturers for better regulation in India. This is most relevant in the context of two recent developments, (a) Notification of medical devices rules, 2017 with classification of ECT as Class C and (b) Recent change in classification of ECT devices by US-FDA in 2018. The establishment of standards would help in upregulating the standard of ECT devices as well as ECT practices.

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.

Mismatch Negativity in Schizophrenia, Unaffected First-degree Relatives, and Healthy Controls.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.