Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.

Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.

Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach.

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records. Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture pre- or early- symptomatic disease trajectories, limiting their utility in characterizing the full natural history of the disease. Therapeutic development in leukodystrophies is subject to these same obstacles. The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) comprises of a network of research institutions across the United States, supported by a multi-center biorepository protocol, to map the longitudinal clinical course of disease across leukodystrophies. As part of GLIA-CTN, we developed Standard Operating Procedures (SOPs) that delineated all study processes related to staff training, source documentation, and data sharing. Additionally, the SOP detailed the standardized approach to data extraction including diagnosis, clinical presentation, and medical events, such as age at gastrostomy tube placement. The key variables for extraction were selected through face validity, and common electronic case report forms (eCRF) across leukodystrophies were created to collect analyzable data. To enhance the depth of the data, clinical notes are extracted into "original" and "imputed" encounters, with imputed encounter referring to a historic event (e.g., loss of ambulation 3 months prior). Retrospective Functional Assessments were assigned by child neurologists, using a blinded dual-rater approach and score discrepancies were adjudicated by a third rater. Upon completion of extraction, data source verification is performed. Data missingness was evaluated using statistics. The proposed methodology will enable us to leverage existing medical records to address the persistent gap in natural history data within this unique disease group, allow for assessment of clinical trajectory both pre- and post-formal diagnosis, and promote recruitment of larger cohorts.

The Variability of Semen Parameters With Sexual Abstinence Using Mail-in Sperm Testing Is Similar to That Seen With Traditional In-Office Semen Analysis.

The impact of ejaculatory abstinence on semen parameters using in-office semen analyses has been well-established; however, their variability has not been evaluated in men using mail-in semen analysis kits. Our study aims to describe how the sperm parameters using mail-in semen analysis tests change with abstinence and validate their equivalence to those seen with in-office semen analysis tests. We retrospectively reviewed the semen analysis results of men using mail-in semen analysis tests provided by Give Legacy, Inc (Legacy) facilities from 2019 to 2021. We collected their demographic information, abstinence duration, and semen parameters (conventional and kinematic) from their records. Semen samples were categorized as normozoospermic and oligozoospermic based on concentration. The shape of the relationship between abstinence duration and semen parameters was assessed via generalized additive models. We have collected 3,469 unique samples provided by 2,609 (75%) normozoospermic men and 860 (25%) oligozoospermic from all over the United States. In normozoospermic men, longer periods of sexual abstinence were linked to higher levels of sperm concentration, total sperm count, and total motile sperm. However, there was a decline in both total and progressive motility. Conversely, in oligozoospermic men, extended periods of abstinence led to a rapid decline in total motile sperm, as well as total and progressive motility. There was no significant correlation observed between sexual abstinence and variations in sperm morphology. Our study shows that variability of sperm parameters with abstinence, as measured through mail-in semen analysis tests, is comparable to the patterns observed with conventional in-office sperm testing.

Influence of comorbid social anxiety disorder in PTSD treatment outcomes for Prolonged Exposure in female military sexual trauma survivors with PTSD.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that frequently presents alongside other comorbid diagnoses. Although several evidence-based psychotherapies have been well-studied for PTSD, limited research has focused on the influence of diagnostic comorbidity on their outcomes. The present study sought to investigate the influence of comorbid social anxiety disorder on treatment outcomes in patients with PTSD. METHODS: One hundred and twelve treatment-seeking female veteran participants with PTSD completed baseline assessments and received 12-15 sessions of Prolonged Exposure. Symptom measures were completed biweekly as well as at immediate posttreatment, 3-month, and 6-month follow-ups. RESULTS: Thirty (26.8%) participants seeking PTSD treatment also met diagnostic criteria for social anxiety disorder. Multilevel modeling was used to examine effects of social anxiety disorder diagnosis on post-intervention symptoms and revealed significantly worse outcomes for symptoms of PTSD and depression in participants with comorbid PTSD and social anxiety disorder. CONCLUSION: Consistent with previous studies of co-occurring PTSD and depression, present findings suggest that comorbid diagnoses may adversely affect disorder-specific treatment outcomes. As such, the presence of diagnostic comorbidity may merit further consideration and potential adaptions to the traditional, disorder-specific assessment and treatment practices for PTSD.

Recurrent episodes of vomiting and diarrhoea in a male child: a rare presentation of X-linked adrenoleukodystrophy.

Recurrent episodes of vomiting and diarrhoea in a child can present as a diagnostic dilemma and be easily misdiagnosed as recurrent viral gastroenteritis episodes. Primary adrenal insufficiency can present with recurrent episodes of vomiting and diarrhoea with the presence of metabolic acidosis and can be life-threatening if left undiagnosed and untreated. A high index of suspicion should be kept for diagnosing primary adrenal insufficiency in a child presenting with recurrent episodes of vomiting and diarrhoea with laboratory evidence of metabolic acidosis and hypoglycaemia. Primary adrenal insufficiency, in a male child specifically, should raise alarm for X-linked adrenoleukodystrophy (X-ALD). Very-long-chain fatty acids and confirmatory genetic testing for an ABCD1 gene mutation can help confirm the diagnosis. Addison's disease often presents prior to the onset of the cerebral form of X-ALD. Early diagnosis of X-ALD allows for MRI screening for the development of cerebral disease in its early stages when treatment with stem cell transplant can halt the disease and be lifesaving.

Rate of Leptomeningeal Enhancement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis.

INTRODUCTION: Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. METHODS: Retrospective review of pediatric MOG-abs patients was performed. RESULTS: Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had leptomeningeal enhancement. Two patients' relapses were manifested by leptomeningeal enhancement alone and another patient presented with seizures, encephalopathy, and aseptic meningitis without demyelinating lesions. Cerebrospinal fluid pleocytosis was seen in both leptomeningeal (4/7 patients) and nonleptomeningeal enhancement (10/14 patients). Interestingly, 3 patients with leptomeningeal enhancement had normal cerebrospinal fluid white blood cell count. Cortical edema was more likely in patients with leptomeningeal enhancement (P = .0263). CONCLUSION: We expand the clinical spectrum of anti-MOG antibody-associated disorder. Patients with recurrent leptomeningeal enhancement without demyelinating lesions should be tested for MOG antibodies.

Leukodystrophies in Children: Diagnosis, Care, and Treatment.

Leukodystrophies are a group of genetically determined disorders that affect development or maintenance of central nervous system myelin. Leukodystrophies have an incidence of at least 1 in 4700 live births and significant morbidity and elevated risk of early death. This report includes a discussion of the types of leukodystrophies; their prevalence, clinical presentation, symptoms, and diagnosis; and current and future treatments. Leukodystrophies can present at any age from infancy to adulthood, with variability in disease progression and clinical presentation, ranging from developmental delay to seizures to spasticity. Diagnosis is based on a combination of history, examination, and radiologic and laboratory findings, including genetic testing. Although there are few cures, there are significant opportunities for care and improvements in patient well-being. Rapid advances in imaging and diagnosis, the emergence of and requirement for timely treatments, and the addition of leukodystrophy screening to newborn screening, make an understanding of the leukodystrophies necessary for pediatricians and other care providers for children.

Influence of Region on Sensory and Chemical Profiles of Pennsylvania Grüner Veltliner Wines.

The influence of cultural and environmental factors on the sensory and chemical profiles of wines has been the subject of research investigation for many years, and an examination of these relationships can help determine whether wine regional trends exist. The present study investigated the chemical and sensory factors that drive regional differences in Pennsylvania Grüner Veltliner wines through a controlled winemaking study across two vintages in 2018 and 2019. Descriptive analysis was used to identify key sensory attributes of Pennsylvania Grüner Veltliner. Intensities of these attributes were evaluated in wines vinified under identical conditions from grapes harvested across nine Pennsylvania vineyards. Chemical profiles of finished wines were examined through volatile, phenolic, and color analyses. Significant sensory differences were found between wine regions, with some trends consistent across both vintages; however, regionality based on compositional analyses was less clear. As the first study to examine Pennsylvania Grüner Veltliner wines sensorially, results revealed sensory characteristics that can be useful for wineries and their tasting room staff in marketing these lesser-known white wines to wine consumers as the variety grows in popularity in the state.

Practical Approaches and Knowledge Gaps in the Care for Children With Leukodystrophies.

Leukodystrophies are a group of neurodegenerative genetic disorders that affect approximately 1 in 7500 individuals. Despite therapeutic progress in individual leukodystrophies, guidelines in neurologic care are sparse and consensus among physicians and caregivers remains a challenge. At patient advocacy meetings hosted by Hunter's Hope from 2016-2018, multidisciplinary experts and caregivers met to conduct a literature review, identify knowledge gaps and summarize best practices regarding neurologic care. Stages of severity in leukodystrophies guided recommendations to address different levels of need based on a newly defined system of disease severity. Four core neurologic domains prioritized by families were identified and became the focus of this guideline: sleep, pain, seizures/epilepsy, and language/cognition. Based on clinical severity, the following categories were used: presymptomatic, early symptomatic, intermediate symptomatic, and advanced symptomatic. Across the leukodystrophies, neurologic care should be tailored to stages of severity while accounting for unique aspects of every disease and multiple knowledge gaps present. Standardized tools and surveys can help guide treatment but should not overburden families.

Lessons Learned in Implementing VA Video Connect for Evidence-Based Psychotherapies for Anxiety and Depression in the Veterans Healthcare Administration.

A top priority for the Veteran's Healthcare Administration is improving access to high-quality mental healthcare. Mobile and telemental healthcare are a vital component of increasing access for veterans. The Veteran's Healthcare Administration is making efforts to further broaden how veterans receive their care through VA Video Connect, which allows veterans to connect with their provider from their residence or workplace. In this mixed-methods study, successes and challenges associated with the rapid implementation of VA Video Connect telemental health appointments are examined through (1) administrative data and (2) qualitative interviews at one medical center. Within 1 year of the telehealth initiative, the number of providers experienced with telemental health increased from 15% to 85%, and telehealth appointments increased from 5376 to 14,210. Provider reported barriers included administrative challenges and concerns regarding care. Having an implementation model of telehealth champions and a team of experienced mental health providers allowed for rapid adoption of telehealth. Utilizing a similar model in other settings will further enable more veterans with depression and anxiety to have access to evidence-based psychotherapy, regardless of location or national crisis. With the dramatic increase in both training for providers as well as veteran use of telemental healthcare during the COVID-19 pandemic response, future research should aim to better understand which teams were able to switch to telehealth easily versus those which struggled, along with examining system-wide and provider-level factors that facilitated continued use of telehealth after social distancing requirements related to COVID-19 were relaxed.

Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome.

BACKGROUND: Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals with SATB2-associated syndrome. METHODS: We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result. For completeness, a supplemental survey was distributed to the caregivers and input from the treating neurologist was obtained whenever possible. RESULTS: Forty-one subjects were identified as having at least one prior abnormal electroencephalography. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six subjects with definite clinical seizures needed polytherapy (35%). Delayed myelination and/or abnormal white matter hyperintensities were seen on neuroimaging in 19 individuals (61%). CONCLUSIONS: Epileptiform abnormalities are commonly seen in individuals with SATB2-associated syndrome. A baseline electroencephalography that preferably includes sleep stages is recommended during the initial evaluation of all individuals with SATB2-associated syndrome, regardless of clinical suspicion of epilepsy.

Randomized Clinical Trial of First-Line Genome Sequencing in Pediatric White Matter Disorders.

OBJECTIVE: Genome sequencing (GS) is promising for unsolved leukodystrophies, but its efficacy has not been prospectively studied. METHODS: A prospective time-delayed crossover design trial of GS to assess the efficacy of GS as a first-line diagnostic tool for genetic white matter disorders took place between December 1, 2015 and September 27, 2017. Patients were randomized to receive GS immediately with concurrent standard of care (SoC) testing, or to receive SoC testing for 4 months followed by GS. RESULTS: Thirty-four individuals were assessed at interim review. The genetic origin of 2 patient's leukoencephalopathy was resolved before randomization. Nine patients were stratified to the immediate intervention group and 23 patients to the delayed-GS arm. The efficacy of GS was significant relative to SoC in the immediate (5/9 [56%] vs 0/9 [0%]; Wild-Seber, p < 0.005) and delayed (control) arms (14/23 [61%] vs 5/23 [22%]; Wild-Seber, p < 0.005). The time to diagnosis was significantly shorter in the immediate-GS group (log-rank test, p = 0.04). The overall diagnostic efficacy of combined GS and SoC approaches was 26 of 34 (76.5%, 95% confidence interval = 58.8-89.3%) in <4 months, greater than historical norms of <50% over 5 years. Owing to loss of clinical equipoise, the trial design was altered to a single-arm observational study. INTERPRETATION: In this study, first-line GS provided earlier and greater diagnostic efficacy in white matter disorders. We provide an evidence-based diagnostic testing algorithm to enable appropriate clinical GS utilization in this population. ANN NEUROL 2020;88:264-273.

Emotional Processing of Imaginal Exposures Predicts Symptom Improvement: Therapist Ratings Can Assess Trajectory in Prolonged Exposure for Posttraumatic Stress Disorder.

Research on mechanisms of change in prolonged exposure therapy (PE), an evidence-based treatment for posttraumatic stress disorder (PTSD), is ongoing. Two putative mechanisms of change are engagement during imaginal exposure and trauma-related belief change. The PE Therapist Questionnaire (PETQ), a novel measure based on the emotional processing theory underlying PE, was developed as a practical tool for therapists to use to assess (a) patient engagement during imaginal exposures and (b) perspective shifts during postimaginal processing. Patients (N = 151) at a U.S. Veterans Affairs medical center PTSD specialty clinic completed self-report measures of PTSD and depression symptoms prior to sessions. Study therapists (n = 17) completed the PETQ postsession. Rational construction and psychometric analyses suggested a two-component solution for the PETQ: imaginal and processing. The imaginal factor did not relate to PTSD and depression symptoms. The processing factor correlated with current and next-session PTSD and depression symptoms, with medium effect sizes, rs = -.41 to -.45, ps < .001. Controlling for current-session PTSD and depression, a higher level of processing predicted lower next-session PTSD severity, with a small effect size, ß = -.38, p < .04. Postexposure emotional processing, which supports positive changes in maladaptive trauma-related beliefs and tolerance of emotional distress, predicted future symptom improvement, highlighting the importance of processing components in PE. Further, the use of therapist observations may offer ancillary methods less influenced by correlation of within-patient subjective ratings and concomitant risk of construct overlap in mechanisms research.

An adjunctive human-animal interaction intervention for veterans with PTSD: study protocol for a randomized controlled trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) rarely remits over time, and if left untreated, leads to significant distress, functional impairment, and increased health care costs. Fortunately, effective evidence-based treatments (EBTs) for PTSD, such as Prolonged Exposure (PE), exist. Despite their availability and efficacy, a significant number of individuals with PTSD do not initiate treatment when offered or dropout prematurely. One proposed theory suggests that the emotional-numbing symptoms of PTSD (e.g., blunted affect, apathy) can serve as a barrier to engaging in, and successfully completing, treatment; and the broad human-animal interaction (HAI) literature available suggests that HAI can potentially reduce emotional numbing related to PTSD. Accordingly, this manuscript describes an ongoing, federally funded, randomized controlled trial testing the efficacy of RESCUE, an HAI intervention, as a viable adjunctive treatment component for PE. METHODS/DESIGN: The study will include 70 veterans with PTSD treated at a Southeastern Veterans Affairs Medical Center (VAMC). All participants in the trial receive up to 12 sessions of PE. Participants are randomly assigned 1:1 to (1) volunteer at a local animal shelter or (2) volunteer at a community agency of their choice as part of their in-vivo exposure exercises for PE. Outcomes will be examined via standard clinical interviews, self-report questionnaires, and thematic interviews. DISCUSSION: It is hypothesized that participants in the HAI condition will report greater decreases in emotional-numbing symptoms and increased treatment compliance and completion rates relative to those in the community volunteer condition. If successful, RESCUE, could be easily incorporated into standard PE and broadly disseminated. TRIAL REGISTRATION: ClinicalTrials.gov. ID: NCT03504722. Retrospectively registered on 2 May 2017.

De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases.

N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role in neuronal development and brain function. Rare genetic variants in the GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize the clinical presentations for 18 patients harboring 12 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M2 re-entrant loop, a region that lines the pore and is intolerant to missense variation. These de novo variants were identified in children with a set of neurological and neuropsychiatric conditions. Evaluation of the receptor cell surface expression, pharmacological properties, and biophysical characteristics show that these variants can have modest changes in agonist potency, proton inhibition, and surface expression. However, voltage-dependent magnesium inhibition is significantly reduced in all variants. The NMDARs hosting a single copy of a mutant subunit showed a dominant reduction in magnesium inhibition for some variants. These variant NMDARs also show reduced calcium permeability and single-channel conductance, as well as altered open probability. The data suggest that M2 missense variants increase NMDAR charge transfer in addition to varied and complex influences on NMDAR functional properties, which may underlie the patients' phenotypes.

Aicardi goutières syndrome is associated with pulmonary hypertension.

While pulmonary hypertension (PH) is a potentially life threatening complication of many inflammatory conditions, an association between Aicardi Goutières syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the development of PH has not been characterized to date. We analyzed the cardiac function of individuals with AGS enrolled in the Myelin Disorders Bioregistry Project using retrospective chart review (n = 61). Additional prospective echocardiograms were obtained when possible (n = 22). An IFN signature score, a marker of systemic inflammation, was calculated through the measurement of mRNA transcripts of type I IFN-inducible genes (interferon signaling genes or ISG). Pathologic analysis was performed as available from autopsy samples. Within our cohort, four individuals were identified to be affected by PH: three with pathogenic gain-of-function mutations in the IFIH1 gene and one with heterozygous TREX1 mutations. All studied individuals with AGS were noted to have elevated IFN signature scores (Mann-Whitney p < .001), with the highest levels in individuals with IFIH1 mutations (Mann-Whitney p < .0001). We present clinical and histologic evidence of PH in a series of four individuals with AGS, a rare interferonopathy. Importantly, IFIH1 and TREX1 may represent a novel cause of PH. Furthermore, these findings underscore the importance of screening all individuals with AGS for PH.

Health-Related Quality of Life for Patients With Genetically Determined Leukoencephalopathy.

BACKGROUND: We attempted to characterize the health-related quality of life in patients with genetically determined leukoencephalopathies as it relates to the severity of clinical features and the presence or absence of a precise molecular diagnosis. METHODS: Health-related quality of life was assessed using the Pediatric Quality of Life Inventory model (Pediatric Quality of Life Inventory 4.0 Self- and Proxy-reports) on 59 patients diagnosed with genetically determined leukoencephalopathies. In total, 38 male and 21 female patients ranging from one to 32 years of age (mean nine years), as well as their parents, completed the Pediatric Quality of Life Inventory health-related quality of life measures. In addition, participants completed detailed standardized clinical assessments or questionnaires. The correlation between health-related quality of life results and the severity of the clinical features, as well as the presence or absence of a molecular diagnosis, were analyzed. RESULTS: Patients with more severe clinical features showed statistically significant lower total Pediatric Quality of Life Inventory scores. More specifically, lower health-related quality of life was noted in children with sialorrhea, gastrostomy, and dystonia and in children who use a wheelchair. CONCLUSIONS: Patients with more severe clinical features experience a lower quality of life. Our study further highlights the importance of addressing both physical and psychosocial issues and discussing perception of quality of life with both parents and children. A larger multicenter prospective study will be needed to further define the burden of these diseases and to identify modifiable factors.

Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene.

BACKGROUND: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene. MATERIALS AND METHODS: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center. RESULTS: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing. CONCLUSIONS: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.

Treatment for Anxiety and Depression via Clinical Videoconferencing: Evidence Base and Barriers to Expanded Access in Practice.

This review summarizes six decades of clinical outcome research relevant to evidence-based practices for depression and anxiety delivered via clinical videoconferencing. The authors conducted a literature search of previous systematic reviews and an updated search of publications specific to anxiety and depression. Overall, strong evidence supports the safety and clinical effectiveness of administering evidence-based psychotherapy for anxiety and depression via clinical videoconferencing among heterogeneous populations and age ranges, and in multiple care settings, with similar outcomes to in-person care. Despite the overall clinical effectiveness of the modality, the authors discuss common logistical and institutional barriers to long-term effective implementation. Future systems-level research is required to investigate replicable and sustainable models for implementing and expanding access to evidence-based psychotherapies via clinical videoconferencing.