The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function, such as planning ability. These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry.

Abnormal serotonergic function is implicated in the pathogenesis of affective disorders. We induced transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), and measured neural activity during different cognitive tasks using positron emission tomography (PET). Neural activity in several 5-HT-related brain areas, e.g., dorsal raphé, habenula, septal region, amygdala, and orbitofrontal cortex, covaried significantly with plasma levels of tryptophan and ratings of depressed mood. Task-specific responses in left amygdala and left anterior cingulate were attenuated by tryptophan depletion. We used these PET data to test the hypothesis that projections from the habenula modulate dorsal raphé activity and that this modulation is enhanced in patients experiencing a profound mood change following serotonergic challenge. A strong linear correlation (r(2) > 0.5) between habenula and raphé activity was observed in subjects with postdepletion ratings >/=10 on a modified Hamilton depression scale, whereas subjects experiencing milder changes in mood had weaker habenula-raphé coupling (r(2) < 0.5). These data support a model of the serotonergic system in which the habenula projection to the raphé represents a convergent feedback pathway that controls the release of 5-HT throughout the brain. In our experiment we were able to engage this system in patients who were sensitive to tryptophan depletion.

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-Acute tryptophan depletion (ATD) is a technique used to study serotonin (5-hydroxytryptamine; 5-HT) brain function in mood disorders. In this paradigm, 5-HT function is temporarily lowered by deprivation of its precursor L -Tryptophan (Trp), an amino acid essential for 5-HT synthesis. It has been suggested that behavioral response to ATD might be informative about the pathophysiology of clinical depression and the mechanisms mediating antidepressant efficacy.A number of studies have demonstrated that ATD temporarily induces depressive symptoms in remitted depressive patients treated with antidepressant medication (Delgado et al. 1990; Spillman et al. 2001). The recurrence of symptoms appears to be highest in subjects treated with a selective serotonin reuptake inhibitor (SSRI) (Delgado et al. 1990(Delgado et al. , 1994(Delgado et al. , 1999.However, not all patients react to ATD; even in SSRItreated patients, ATD exacerbates symptoms in 50-60% of investigated patients (Van der Does 2001a). This raises the question of what factors determine response to ATD. It has been argued that induced depressive

Background The 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. Objective The 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. Methods We 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. Results Findings 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. Conclusions We 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.

A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit The Parkinson Study Group QE3 Investigators IMPORTANCE Coenzyme 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. OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS A 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. INTERVENTIONS The 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 MEASURES Participants 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. RESULTS The 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 RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, bu...