Abnormal Involuntary Movement Scale Research Articles

Testing a Motor Score Based on PANSS Ratings: A Proxy for Comprehensive Motor Assessment.

Abnormal psychomotor behavior is a core schizophrenia symptom. However, assessment of motor abnormalities with expert rating scales is challenging. The Positive and Negative Syndrome Scale (PANSS) includes 3 items broadly related to hypokinetic motor behavior. Here, we tested whether a sum score of the PANSS items mannerisms and posturing (G5), motor retardation (G7), and disturbance of volition (G13) corresponds to expert ratings, potentially qualifying as a proxy-marker of motor abnormalities. Combining baseline datasets (n = 196) of 2 clinical trials (OCoPS-P, BrAGG-SoS), we correlated PANSS motor score (PANSSmot) and 5 motor rating scales. In addition, we tested whether the cutoff set at ≥3 on each PANSS motor item, ie, "mild" on G05, G07, and G13 (in total ≥9 on PANSSmot) would differentiate the patients into groups with high vs low scores in motor scales. We further sought for replication in an independent trial (RESIS, n = 102), tested the longitudinal stability using week 3 data of OCoPS-P (n = 75), and evaluated the validity of PANSSmot with instrumental measures of physical activity (n = 113). PANSSmot correlated with all motor scales (Spearman-Rho-range 0.19-0.52, all P ≤ .007). Furthermore, the cutoff set at ≥3 on each PANSS motor item was able to distinguish patients with high vs low motor scores in all motor scales except using Abnormal Involuntary Movement Scale (Mann-Whitney-U-Tests: all U ≥ 580, P ≤ .017). Our findings suggest that PANSSmot could be a proxy measure for hypokinetic motor abnormalities. This might help to combine large datasets from clinical trials to explore whether some interventions may hold promise to alleviate hypokinetic motor abnormalities in psychosis.

Efficacy and Safety of Valbenazine in Elderly and Nonelderly Japanese Patients With Tardive Dyskinesia: A Post Hoc Analysis of the J-KINECT Study.

The efficacy and safety of valbenazine, a selective vesicular monoamine transporter 2 inhibitor, has been confirmed for treatment of tardive dyskinesia (TD) in patients aged ≥65 years in non-Asian clinical trials; however, data are lacking in elderly Asian patients. This post hoc analysis of J-KINECT aimed to evaluate the efficacy and safety of valbenazine in elderly Japanese patients with TD. J-KINECT was a randomized, double-blind, placebo-controlled study with a 6-week double-blind, placebo-controlled period; 42-week double-blind, valbenazine extension period; and 4-week posttreatment observation period. Outcomes were summarized by age (≥65 years [elderly] and <65 [nonelderly]) and treatment group. The safety analysis set included 100 and 153 patients aged ≥65 and <65 years, respectively (intention-to-treat set: 98 and 151 patients, respectively). In the elderly group, the difference versus placebo in least-squares mean change from baseline in the Abnormal Involuntary Movement Scale total score at week 6 was -3.1 (95% confidence interval: -4.5, -1.7) and -5.5 (-7.0, -3.9) with valbenazine 40 and 80 mg, respectively; in the nonelderly group, respective differences were -1.5 (-2.6, -0.4) and -2.5 (-3.6, -1.3). Both age groups showed improvement in Clinical Global Impression of Change-Tardive Dyskinesia scores with valbenazine. The incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation was higher in the elderly versus nonelderly group. There was no trend toward higher incidences of TEAEs or related TEAEs in the elderly group. The findings suggest that valbenazine may be used effectively and safely as a treatment for TD, even in elderly patients.

Evolution of Movement Disorders in Patients With CLN2-Batten Disease Treated With Enzyme Replacement Therapy.

Neuronal ceroid lipofuscinosis type 2 (CLN2-disease) is an inherited childhood-onset neurodegenerative condition, with classical early features of speech delay, epilepsy, myoclonus, ataxia, and motor regression. This study aimed to better characterize the spectrum of movement disorders in CLN2-disease in a cohort of children receiving enzyme replacement therapy (ERT). A cohort of 18 children attending a single center for treatment with cerliponase alfa ERT was systematically assessed using a standardized structured history and a double-scored, video-recorded examination using the Unified Batten Disease Rating Scale (UBDRS) and Abnormal Involuntary Movement Scale. Noncanonical movement disorders are common: while ataxia (89%) and myoclonus (83%) were near-universal, spasticity and dystonia were experienced by over half (61% each), with children having a median of 4 distinct movement disorder phenotypes. This progression was stereotyped with initial ataxia/myoclonus, then hyperkinesia/spasticity, and later hypokinesia. ERT slows progression of movement disorders, as measured by the UBDRS physical subscale, with 1.45 points-per-month progression before diagnosis and 0.44 points-per-month while on treatment (p = 0.019). Movement disorders are a core feature of CLN2-disease and follow a typical pattern of progression which is slowed by ERT. Identifying and treating movement disorders should become standard, especially given increased patient survival.

A Model-Informed Drug Development Approach Supporting the Approval of an Unstudied Valbenazine Dose for Patients With Tardive Dyskinesia.

Valbenazine is a highly potent and selective inhibitor of synaptic vesicular monoamine transporter 2. The current therapeutic doses of valbenazine for tardive dyskinesia (TD) are 40, 60, or 80 mg capsules, given orally, once daily (QD). While 40 and 80 mg were investigated in phase 3 KINECT® 3 trial and initially approved, the approval of valbenazine 60mg was based on the analysis utilizing the Model-informed drug development (MIDD) approach, facilitated through the US Food and Drug Administration's MIDD Pilot Program. This study aimed to demonstrate the efficacy of 60 mg QD dose through model simulations using an established exposure-response (E-R) relationship between valbenazine active metabolite [+]-α-dihydrotetrabenazine exposure and the change from baseline in Abnormal Involuntary Movement Scale total score (AIMS-CFB). A longitudinal E-R model was constructed based on the 40 and 80 mg data from the KINECT 3 trial. The final Emax model adequately predicted dose-dependent improvement in the primary endpoint and was used to interpolate AIMS-CFB for 60 mg at week 6. The efficacy of the unstudied 60 mg dose regimen is expected to be within the range of doses studied clinically with predicted mean AIMS-CFB (95% confidence interval) of -2.69 (-3.30, -2.13) between observed mean AIMS-CFB for 40 mg of -1.92 and 80 mg of -3.39. Results from this analysis provided the key evidence to establish efficacy of 60 mg QD without the need for an additional clinical trial. The availability of valbenazine 60mg dose fills an existing medical need for patients with TD who could benefit from this third effective dose.

Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia

ObjectiveThis study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. MethodsSixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. ResultsOf the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). ConclusionsTDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SignificanceThis study provides a novel perspective for the clinical treatment of patients with TD.

Tardive Dyskinesia with Antipsychotic Medication in Children and Adolescents: A Systematic Literature Review.

Tardive dyskinesia (TD) is a persisting, and potentially irreversible, movement disorder associated with treatment with dopamine receptor antagonists. Few data are available on the risk of TD in children and adolescents treated with antipsychotic medication. To review the literature on incidence, risk factors, and treatment options for antipsychotic-associated TD in children and adolescents (aged < 18 years). Relevant articles were identified through a systematic search of Embase and Medline performed in January 2024. Methodological quality was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute Critical Appraisal tools. Thirteen studies were identified. The reported TD point prevalence was 5-20%, with higher rates in studies involving typical antipsychotics. Lower estimates (around 1%) emerged from analyses of clinical database data suggesting underdiagnosis in clinical practice. Risk factors included treatment with typical antipsychotics, higher doses, longer duration of exposure, older age, female gender, higher baseline Abnormal Involuntary Movements Scale (AIMS) scores, intellectual impairment, and perinatal complications. Although relatively few cases have been reported in children and adolescents, TD remains a risk in this population. Individuals receiving antipsychotics should be monitored carefully for the emergence of abnormal movements. Other than dose reduction, discontinuation, or switch to a lower-risk antipsychotic, few interventions have demonstrated efficacy. The strongest evidence for pharmacological treatment is for VMAT-2 inhibitors (valbenazine and deutetrabenazine), but these drugs are not licensed for use in children. To reduce risk, antipsychotics should be prescribed only if necessary, at the minimum effective dose and for the minimum necessary duration.

Fenobam modulates distinct electrophysiological mechanisms for regulating excessive gamma oscillations in the striatum of dyskinetic rats

Gamma oscillations have been frequently observed in levodopa-induced dyskinesia (LID), manifest as broadband (60-120 Hz) and narrowband (80-110 Hz) gamma activity in cortico-striatal projection. We investigated the electrophysiological mechanisms and correlation of gamma oscillations with dyskinesia severity, while assessing the administration of fenobam, a selective metabotropic glutamate receptor 5 (mGluR5) antagonist, in regulating dyskinesia-associated gamma activity. We conducted simultaneous electrophysiological recordings in Striatum (Str) and primary motor cortex (M1), together with Abnormal Involuntary Movement Scale scoring (AIMs). Phase-amplitude coupling (PAC), power, coherence, and Granger causality analyses were conducted for electrophysiological data. The findings demonstrated increased beta oscillations with directionality from M1 to Str in parkinsonian state. During on-state dyskinesia, elevated broadband gamma activity was modulated by the phase of theta activity in Str, while M1 → Str gamma causality mediated narrowband gamma oscillations in Str. Striatal gamma power (both periodic and aperiodic power), periodic power, peak frequency, and PAC at 80 min (corresponding to the peak dyskinesia) after repeated levodopa injections across recording days (day 30, 33, 36, 39, and 42) increased progressively, correlating with total AIMs. Additionally, a time-dependent parabolic trend of PAC, peak frequency and gamma power was observed after levodopa injection on day 42 from 20 to 120 min, which also correlated with corresponding AIMs. Fenobam effectively alleviates dyskinesia, suppresses enhanced gamma oscillations in the M1-Str directionality, and reduces PAC in Str. The temporal characteristics of gamma oscillations provide parameters for classifying LID severity. Antagonizing striatal mGluR5, a promising therapeutic target for dyskinesia, exerts its effects by modulating gamma activity.

Sustained Treatment Response and Global Improvements With Long-term Valbenazine in Patients With Tardive Dyskinesia.

Using data from KINECT® 4, a phase 3, 48-week study of valbenazine, post hoc analyses were conducted to assess long-term outcomes that are relevant to the real-world management of tardive dyskinesia (TD). Post hoc analyses of the participants of the KINECT 4 study who completed 48 weeks of open-label valbenazine (40 or 80 mg) treatment were conducted. Valbenazine effects on TD were evaluated using the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD), and Patient Global Impression of Change (PGIC). Of 103 participants completing 48 weeks of treatment, 55% experienced clinically meaningful improvement (defined as ≥2-point reduction in AIMS total score [sum of items 1 - 7, evaluated by site raters]) by week 4; at week 48, 97% met this threshold. The percentage of completers who achieved AIMS total score response thresholds of ≥10% to ≥90% increased over time, with 86% of completers reaching ≥50% improvement. Of the 40 (39%) completers with AIMS ≥50% response at week 8, 38 (95%) sustained this response at week 48; 81% of those who did not meet this threshold at week 8 had achieved it by week 48. At week 48, more than 85% of completers achieved CGI-TD and PGIC ratings of "much improved" or "very much improved." The majority of participants who completed 48 weeks of treatment with once-daily valbenazine experienced substantial clinically meaningful and sustained TD improvements. These findings indicate that valbenazine can be a highly effective long-term treatment in patients with TD.

The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease

Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague–Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.

Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia.

The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133. The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA. The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p=0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores. Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson’s Disease

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson’s disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients’ individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 – 0.047]. Along with the levodopa challenge test, patients’ age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 – -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered

Successful treatment of cranial dystonia using a Zolpidem+Melatonin combination: A video case-series

Cranial dystonias (CrD) are challenging to treat. Oral pharmacotherapy is often sub-optimal, while delicate anatomy and limited availability of skilled botulinum toxin injectors makes this approach risky, and often difficult to access; neurosurgical options e.g. deep brain stimulation, are high-risk in the elderly populations most affected. We observed significant improvement in CrD in 2 patients prescribed Zolpidem+Melatonin combination treatment for insomnia, and therefore trialled this treatment in a further 4 patients with CrD. Six patients were treated with Zolpidem+Melatonin. Pre- and post-treatment videotaped clinical examinations were blindly rated by an independent assessor (EM) and scored using the 'Facial and Oral Movements' section of the abnormal involuntary movements scale (AIMS), as well as the Jankovic rating scale for blepharospasm. Dystonic features, as measured by the abnormal involuntary movements scale (AIMS) improved by an average of 75% after treatment (6.5±3.1 before treatment to 1.7 +/- 0.8 after treatment). Improvements were also observed in blepharospasm severity scores, and in cervical dystonic features. Zolpidem+Melatonin combination treatment represents a safe and effective treatment for CrD. Low cost and wide availability makes it an attractive option, particularly in resource-constrained healthcare settings, or in patients who have failed, or lack access to alternatives.

Association of dopamine receptor D3 polymorphism with Levodopa-induced Dyskinesia: A study on Parkinson’s disease patients from India

IntroductionLevodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson’s disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation. Methods and materials200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson’s Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques. ResultsThe frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 – 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002). ConclusionWe observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research

BackgroundMinimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures. ObjectivesTo provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder. MethodsWe conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales. Results2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD). ConclusionThis review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.

Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study.

Preclinical evidence suggests that co-administration of the 5-HT1A agonist buspirone and the 5-HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak-effect dyskinesia. Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: -4.2 [-6.1, -2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [-0.1, 1.3]). No serious adverse events were reported. In this proof-of-concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.

The Tardive Dyskinesia Impact Scale (TDIS), a novel patient-reported outcome measure in tardive dyskinesia: development and psychometric validation

BackgroundTardive dyskinesia (TD), a movement disorder in which patients experience abnormal involuntary movements, can have profound negative impacts on physical, cognitive, and psychosocial functioning. The Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is considered the gold standard for evaluating treatment efficacy in TD clinical trials. However, it provides little information about the impacts of uncontrolled movements from a patient perspective and can be cumbersome to administer in clinical settings. The Tardive Dyskinesia Impact Scale (TDIS) was developed as a patient-reported outcome measure to fulfill the need for a disease-specific impact assessment in TD. The objective of the present study was to develop and evaluate the psychometric properties of the TDIS to determine whether it is fit-for-purpose to measure TD impact.MethodsData from qualitative studies and phase 3 trials of a VMAT2 inhibitor for the treatment of TD (KINECT3 and KINECT4) were used to determine the psychometric properties of the TDIS. Qualitative research included concept elicitation and cognitive debriefing interviews with TD patients and their caregivers in order to assess how well the TDIS captured key domains of TD impact. Quantitative analyses to examine the psychometric properties of the TDIS included assessing construct validity (factor structure, known groups, and predictive validity) and responsiveness to change.ResultsQualitative results showed that the TDIS captures the key TD impacts reported by patients and caregivers and that the TDIS was interpreted as intended and relevant to patients’ experiences. Quantitative results found evidence of 2 underlying domains of the TDIS: physical and socioemotional (Comparative Fit Index > 0.9). Known groups and predictive validity indicated that, compared with the AIMS, the TDIS captures unique content (correlation between AIMS and TDIS = 0.2–0.28). The TDIS showed responsiveness to change in treatment, with TDIS scores improving over 48 weeks in the 2 phase 3 trials.ConclusionsThe TDIS captures relevant information about the impact of TD and is easily administered in a clinician’s office or patient’s home. It may be used longitudinally to show changes in TD burden over time. The TDIS complements the AIMS; using these assessments together provides a more holistic assessment of TD.

Associations between Catechol-O-methyltransferase (COMT) polymorphisms and cognitive impairments, psychiatric symptoms and tardive dyskinesia in schizophrenia

IntroductionCatechol-O-methyltransferase (COMT) is a crucial enzyme involved in dopamine metabolism and has been implicated in the etiology of tardive dyskinesia (TD). We aimed to investigate the associations between COMT gene polymorphisms and the occurrence and severity of TD in a Chinese population, as well as the impact on the psychiatric symptoms and cognitive impairments observed in TD patients. MethodsA total of 216 chronic schizophrenia patients, including 59 TD patients and 157 NTD patients, were recruited for this study. Three SNPs of the COMT gene (rs4680, rs165599 and rs4818) were selected and genotyped using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). TD severity, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. ResultsIn TD patients, total AIMs scores were higher in carriers of the rs4680 AA genotype than in carriers of the AG and GG genotypes (p = 0.01, 0.006), carriers of the rs4818 GC and CC genotypes had higher orofacial scores than in GG genotypes (p = 0.032, 0.002). In male TD patients, carriers of the rs165599 GA genotype scored lower in the extremities and trunk scores than AA genotype carriers (p = 0.015). Moreover, in male TD patients, COMT rs4818 was associated with cognition, since the C allele carriers had significantly higher immediate memory (p = 0.043) and verbal function (p = 0.040) scores than the G allele carriers. In addition, rs165599 genotype interacted with TD diagnosis on depressed factor (p = 0.031). ConclusionWithin the Chinese population, COMT gene polymorphisms could potentially serve as biomarkers for the symptoms and prognosis of TD patients.

Evaluation of antipsychotic monitoring in a community health center during the COVID‐19 pandemic

AbstractBackgroundThe coronavirus disease 2019 (COVID‐19) pandemic complicated providers' ability to appropriately monitor patients on antipsychotic medications, as visits moved to telehealth. Adverse metabolic and movement effects can be difficult to assess virtually, reducing adherence to national antipsychotic guidelines. This review was conducted to evaluate provider adherence to antipsychotic medication monitoring during the COVID‐19 pandemic, educate providers on the proper antipsychotic monitoring methods, and then reassess adherence to guidelines.MethodsThis was a retrospective chart review of patients receiving antipsychotics from mental health (MH) and primary care (PC) providers consisting of three phases. Providers prescribing antipsychotics between June 1, 2021, and June 1, 2022, were included in phase one. Patients were reviewed for relevant data including demographics, antipsychotic(s) prescribed, glucose, hemoglobin A1c, total cholesterol, low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, weight/ body mass index (BMI), waist circumference, Abnormal Involuntary Movement Scale (AIMS), and other movement disorder assessments. Providers were then given an educational flyer outlining proper antipsychotic monitoring in October 2022 as phase two. During phase three, providers prescribing antipsychotics between October 1, 2022, and February 23, 2023, were included for review. Monitoring rates were compared to national antipsychotic guidelines, and adherence rates were calculated for each monitoring parameter. Comparisons between phase one and phase three were performed using Chi‐squares to determine statistically significant differences (p &lt; 0.05).ResultsUnfortunately, most monitoring rates decreased from baseline to follow‐up. All metabolic parameters were statistically significantly lower in the follow‐up sample compared to the baseline sample. These differences were seen when comparing the overall sample as well as the MH and PC provider groups across time points. Movement disorder monitoring showed no statistically significant differences between timepoints, with one exception. Among PC providers, the rate of AIMS monitoring was significantly increased from baseline (0%) to follow‐up (11.1%, p = 0.000).ConclusionPharmacist passive education of clinicians alone did not provide a significant change in provider's adherence to antipsychotic monitoring.

Genetic Susceptibility to Tardive Dyskinesia and Cognitive Impairments in Chinese Han Schizophrenia: Role of Oxidative Stress-Related and Adenosine Receptor Genes.

Tardive dyskinesia (TD) is a severe rhythmic movement disorder caused by long-term antipsychotic medication in chronic patients with schizophrenia (SCZ). We aimed to investigate the association between polymorphisms in oxidative stress-related genes (GSTM1, SOD2, NOS1, and NOS3) and adenosine receptor gene (ADORA2A), as well as their interactions, with the occurrence and severity of TD, and cognitive impairments in a Chinese Han population of SCZ patients. Two hundred and sixteen SCZ patients were recruited and divided into TD group (n=157) and non-TD group (n=59). DNA extraction was performed by a high-salt method, followed by SNP genotyping using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The severity of TD, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively. The combination of GSTM1-rs738491, NOS1-rs738409 and ADORA2A-rs229883 was identified as the best three-point model to predict TD occurrence (p=0.01). Additionally, GSTM-rs738491 CC or NOS3-rs1800779 AG genotypes may be protective factors for psychiatric symptoms in TD patients. TD patients carrying the NOS1-rs738409 AG or ADORA2A-rs229883 TT genotypes exhibited poorer cognitive performance. Our findings suggest that the interaction of oxidative stress-related genes and adenosine receptor gene may play a role in the susceptibility and severity of TD in Chinese Han SCZ patient. Furthermore, these genes may also affect the psychiatric symptoms and cognitive function of TD patients.

Regional Homogeneity in schizophrenia patients with tardive dyskinesia: a resting-state fMRI study

Neuronal degeneration and apoptosis may play an important role in the pathogenesis of tardive dyskinesia (TD). Previous studies suggested brain structural and functional abnormalities in patients with TD. We investigated changes in cerebral regional homogeneity (ReHo) in patients with TD using resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were collected from schizophrenia patients with TD (TD group, n=58) and without TD (non-TD group, n=66) and healthy controls (HC group, n=67), processed with SPM, and evaluated at a corrected threshold. Psychopathology and severity of TD were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Results: TD vs. non-TD group showed significantly higher ReHo in the Left Inferior Semilunar Lobule and Right Fusiform Gyrus and lower ReHo in Left Supramarginal Gyrus, Right Inferior Tempotal Gyrus, and Left Medial Frontal Gyrus. The ReHo value in the Left Inferior Semilunar Lobule was negatively correlated with AIMS upper limbs scores. Conclusions: The findings suggest altered regional neural connectivities in association with TD and may inform research of the etiology and monitor the course of TD in patients with schizophrenia and potentially other psychotic disorders.