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IntroductionAnkG, encoded by the ANK3 gene, is a multifunctional scaffold protein with complex isoform expression: the 480 and 270 kDa isoforms have roles at the axon initial segment and node of Ranvier, whereas the 190 kDa isoform (AnkG-190) has an emerging role in the dendritic shaft and spine heads. All isoforms of AnkG undergo palmitoylation, a post-translational modification regulating protein attachment to lipid membranes. However, palmitoylation of AnkG-190 has not been investigated in dendritic spines. The ANK3 gene and altered expression of AnkG proteins are associated with a variety of neuropsychiatric and neurodevelopmental disorders including bipolar disorder and are implicated in the lithium response, a commonly used mood stabilizer for bipolar disorder patients, although the precise mechanisms involved are unknown.ResultHere, we showed that Cys70 palmitoylation stabilizes the localization of AnkG-190 in spine heads and at dendritic plasma membrane nanodomains. Mutation of Cys70 impairs AnkG-190 function in dendritic spines and alters PSD-95 scaffolding. Interestingly, we find that lithium reduces AnkG-190 palmitoylation thereby increasing its mobility in dendritic spines. Finally, we demonstrate that the palmitoyl acyl transferase ZDHHC8, but not ZDHHC5, increases AnkG-190 stability in spine heads and is inhibited by lithium.DiscussionTogether, our data reveal that palmitoylation is critical for AnkG-190 localization and function and a potential ZDHHC8/AnkG-190 mechanism linking AnkG-190 mobility to the neuronal effects of lithium.

Educators have used narrative fiction to expand knowledge and facilitate awareness about underrepresented populations, including those with disabilities. This study is a content analysis of nine award-winning young-adult narrative fiction books with characters depicting individuals with ASD. The analysis yielded a total of 285 symptoms that were coded based on the American Psychiatric Association's definition of ASD symptoms. Analysis revealed that 72% of the total symptoms depicted repetitive or restrictive behaviors, and the remaining 28% represented social communication difficulties or deficits as described by the DSM-5. The results of this study show that few fictional stories depict the difficulties of social communication as it is often observed in high-functioning individuals with ASD. Therefore, narrative fiction that overplays the restrictive, repetitive behaviors and underplays the social communication deficits perpetuates misconceptions about ASD. Narrative fiction with main characters clearly shows ASD symptoms have large implications for stakeholders working with students with ASD.

ImportanceCoenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.ObjectiveTo examine whether CoQ10 could slow disease progression in early PD.Design, setting, and participantsA phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.InterventionsThe remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.Main outcomes and measuresParticipants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.ResultsThe baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo).Conclusions and relevanceCoenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.Trial registrationclinicaltrials.gov Identifier: NCT00740714.

ImportanceCoenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.ObjectiveTo examine whether CoQ10 could slow disease progression in early PD.Design, setting, and participantsA phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.InterventionsThe remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.Main outcomes and measuresParticipants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.ResultsThe baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo).Conclusions and relevanceCoenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.Trial registrationclinicaltrials.gov Identifier: NCT00740714.

BackgroundThe coronavirus disease (COVID-19) presents unique challenges in health care, including mental health care provision. Telepsychiatry can provide an alternative to face-to-face assessment and can also be used creatively with other technologies to enhance care, but clinicians and patients may feel underconfident about embracing this new way of working. ObjectiveThe aim of this paper is to produce an open-access, easy-to-consult, and reliable source of information and guidance about telepsychiatry and COVID-19 using an evidence-based approach. MethodsWe systematically searched existing English language guidelines and websites for information on telepsychiatry in the context of COVID-19 up to and including May 2020. We used broad search criteria and included pre–COVID-19 guidelines and other digital mental health topics where relevant. We summarized the data we extracted as answers to specific clinical questions. ResultsFindings from this study are presented as both a short practical checklist for clinicians and detailed textboxes with a full summary of all the guidelines. The summary textboxes are also available on an open-access webpage, which is regularly updated. These findings reflected the strong evidence base for the use of telepsychiatry and included guidelines for many of the common concerns expressed by clinicians about practical implementation, technology, information governance, and safety. Guidelines across countries differ significantly, with UK guidelines more conservative and focused on practical implementation and US guidelines more expansive and detailed. Guidelines on possible combinations with other digital technologies such as apps (eg, from the US Food and Drug Administration, the National Health Service Apps Library, and the National Institute for Health and Care Excellence) are less detailed. Several key areas were not represented. Although some special populations such as child and adolescent, and older adult, and cultural issues are specifically included, important populations such as learning disabilities, psychosis, personality disorder, and eating disorders, which may present particular challenges for telepsychiatry, are not. In addition, the initial consultation and follow-up sessions are not clearly distinguished. Finally, a hybrid model of care (combining telepsychiatry with other technologies and in-person care) is not explicitly covered by the existing guidelines. ConclusionsWe produced a comprehensive synthesis of guidance answering a wide range of clinical questions in telepsychiatry. This meets the urgent need for practical information for both clinicians and health care organizations who are rapidly adapting to the pandemic and implementing remote consultation. It reflects variations across countries and can be used as a basis for organizational change in the short- and long-term. Providing easily accessible guidance is a first step but will need cultural change to implement as clinicians start to view telepsychiatry not just as a replacement but as a parallel and complementary form of delivering therapy with its own advantages and benefits as well as restrictions. A combination or hybrid approach can be the most successful approach in the new world of mental health post–COVID-19, and guidance will need to expand to encompass the use of telepsychiatry in conjunction with other in-person and digital technologies, and its use across all psychiatric disorders, not just those who are the first to access and engage with remote treatment.