Astrogliosis marker 11C-SL25.1188 PET in traumatic brain injury with persistent symptoms.

Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume (11C-SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with 11C-SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC 11C-SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. 11C-SL25.1188 VT was greater in TBI in PFC (P = 0.00064) and cortex (P = 0.00038). PFC 11C-SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r = -0.48, P = 0.01). In participants scanned within 2 years of last TBI, PFC 11C-SL25.1188 VT correlated with serum glial fibrillary acid protein (r = 0.51, P = 0.037) and total tau (r = 0.74, P = 0.001). Elevated 11C-SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

A Collaborative-Care Telephone-Based Intervention for Depression, Anxiety, and at-Risk Drinking in Primary Care: The PARTNERs Randomized Clinical Trial.

BACKGROUND: Collaborative care (CC) could improve outcomes in primary care patients with common mental conditions. We assessed the effectiveness of a transdiagnostic model of telephone-based CC (tCC) delivered by lay providers to primary care patients with depression, anxiety, or at-risk drinking. METHODS: PARTNERS was a pragmatic trial in 502 primary care adults presenting with depressive symptoms, anxiety symptoms, or at-risk drinking randomized to (1) usual care by primary care providers (PCPs) enhanced with the results of computer-assisted telephone-based assessments (at baseline and 4, 8, and 12 months later) (enhanced usual care [eUC]) or (2) tCC consisting of eUC plus frequent telephone coaching and psychoeducation provided by mental health technicians who also communicated to the PCP recommendations from a psychiatrist for evidence-based pharmacotherapy, psychotherapy, or, when indicated, referrals to mental health services. The primary analysis compared the change on the 9-item Patient Health Questionnaire (PHQ-9) in participants presenting with depression (n = 366) randomized to tCC versus eUC. Secondary analyses compared changes on the Generalized Anxiety Disorder-7 scale (GAD-7) in those presenting with anxiety (n = 298); or change in the number of weekly drinks in those presenting with at-risk drinking (n = 176). RESULTS: There were no treatment or time×treatment effects between tCC and eUC on PHQ-9 scores for patients with depression during the 12-month follow-up. However, there was a treatment effect (tCC > eUC) on GAD-7 scores in those with anxiety and a time×treatment interaction effect on the number of weekly drinks (tCC > eUC) in those with at-risk drinking. CONCLUSION: Implementing transdiagnostic tCC for common mental disorders using lay providers appears feasible in Canadian primary care. While tCC was not better than eUC for depression, there were some benefits for those with anxiety or at-risk drinking. Future studies will need to confirm whether tCC differentially benefits patients with depression, anxiety, or at-risk drinking.

Astrogliosis marker [11C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms.

BACKGROUND: After acute COVID-19, five percent of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective is to measure [11C]SL25.1188 total distribution volume ([11C]SL25.1188 VT), index of monoamine oxidase B (MAO-B) density and marker of astrogliosis with PET in COVID-DC and compare to healthy controls. METHODS: In 21 COVID-DC cases and 21 healthy controls, [11C]SL25.1188 VT was measured in prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum. Depressive symptoms were measured with the Beck Depression Inventory-II and cognitive symptoms were measured with neuropsychological tests. RESULTS: [11C]SL25.1188 VT was higher in COVID-DC in prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum compared to healthy controls. Depressive symptom severity correlated negatively with [11C]SL25.1188 VT across prioritized brain regions. More recent acute COVID-19 correlated positively with [11C]SL25.1188 VT, reflecting higher values since predominance of the omicron variant. Exploratory analyses found greater [11C]SL25.1188 VT in hippocampus, dorsal putamen, and ventral striatum compared to major depressive episode controls with no history of COVID-19; and no relationship to cognitive testing in prioritized regions. CONCLUSIONS: Results strongly support the presence of MAO-B labelled astrogliosis in COVID-DC throughout the regions assessed although the association of greater astrogliosis with less symptoms raises the possibility of a protective role. Magnitude of astrogliosis in COVID-DC is greater since emergence of omicron variant.

Increased sympathetic tone is associated with illness burden in bipolar disorder.

BACKGROUND: We recently described an association between reduced heart rate variability (HRV) and illness burden in bipolar disorder (BD) using a novel Illness Burden Index (IBI). We aimed to further characterize this association by using spectral analyses to assess whether the IBI is also associated with autonomic imbalance in BD patients. METHODS: In this cross-sectional study, 53 participants with BD wore a device for 24 h to assess association between HRV spectral measures and the IBI or each of its components (age of onset, number and type of previous episode(s), duration of the most severe episode, history of suicide attempts or psychotic symptoms during episodes, co-morbid psychiatric disorders, and family history). We ran both unadjusted models and models controlling for age, sex, years of education, marital status, BMI, pharmacotherapy, and baseline functional cardiovascular capacity. RESULTS: HRV low-frequency (LF) normalized values were almost twice as high as published in healthy controls. Higher IBI was associated with higher LF and lower High Frequency (HF) values, resulting in a higher LF/HF ratio, indicating an increased sympathetic tone. Four individual components of the IBI were similarly associated with measures of increased sympathetic tone: earlier age of onset, number of depressive episodes, co-morbid anxiety disorders, and family history of suicide. Adjusted and unadjusted models had similar results. LIMITATIONS: Our models used mean LF and HF and do not consider their dynamic variations over 24 h or phase of the illness. CONCLUSIONS: Burden of illness is associated with increased sympathetic tone in patients with BD, putting them at risk for arrythmias and sudden death.

Metabolic function in patients with bipolar depression receiving anti-inflammatory agents: Findings from the MINDCARE study, a multicentre, randomised controlled trial.

BACKGROUND: Metabolic dysfunction is prevalent in bipolar disorder (BD) and associated with illness severity and treatment outcomes. There is little research exploring this relationship in low and middle-income countries (LMICs) and little is known about the moderating effect of metabolic health on treatment response to anti-inflammatory drugs in BD. METHODS: MINDCARE, a randomized-controlled-trial conducted in Pakistan, investigated the efficacy of minocycline and celecoxib in 266 adults with bipolar depression. This secondary analysis evaluated the association between depression severity at baseline and treatment outcome with metabolic parameters including body mass index (BMI), waist circumference (WC), heart rate (HR), systolic blood pressure (s-BP), and diastolic blood pressure (d-BP). Depression severity was measured using the Hamilton Depression Rating Scale-17. The exploratory aim was to assess whether treatment impacted change in metabolic variables. Associations were evaluated using linear regression. RESULTS: Higher BMI (B=-0.38, 95%CI: -0.55 to -0.21) and WC (B=-0.68, 95%CI: -0.97 to -0.39) were associated with lower baseline depression severity in both the unadjusted and the adjusted models. Baseline metabolic parameters were not associated with treatment response to minocycline or celecoxib nor did treatment significantly impact metabolic variables. LIMITATIONS: Our sample represents patients in an RCT and may not be fully representative of the overall BD population in Pakistan. CONCLUSIONS: Our findings indicate a potential association of poor metabolic health and lower severity of bipolar depression but not treatment outcomes. Future work should evaluate potential relationships of metabolic parameters and BD in diverse populations to increase the transferability of this line of work.