COVID-19 and Suicide: A Deadly Association.

ABSTRACT: COVID-19 hit the world amidst an unprecedented suicide epidemic in this century. As the world focuses on limiting the spread of the virus and prioritizing acutely medically ill patients, containment measures are not without mental health consequences. With rising anxiety and depression, risk of suicide-acutely and in the aftermath of the pandemic-also rises. This article aims to shed light on this major public health problem and better understand what factors may create or exacerbate psychiatric symptoms and suicide. We review suicide data predating the pandemic and examine impact of previous epidemics on suicide rates. We then focus on the current pandemic's impacts and the world's response to COVID-19. We examine how these may lead to increased suicide rates, focusing on the US population. Finally, we offer suggestions on mitigating interventions to curb the impending rise in suicide and the resultant increased burden on an already stretched health care system.

Anterior-posterior gradient differences in lobar and cingulate cortex cerebral blood flow in late-life depression.

Vascular pathology is common in late-life depression, contributing to changes in cerebral function. We examined whether late-life depression was associated with differences in cerebral blood flow (CBF) and whether such differences were related to vascular risk and cerebrovascular pathology, specifically white matter hyperintensity (WMH) volumes. Twenty-three depressed elders and 20 age- and sex-matched elders with no psychiatric history completed cranial 3T MRI. MRI procedures included a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition obtained while on room air and during a hypercapnia challenge allowing for calculation of cerebrovascular reactivity (CVR). Brain segmentation identified frontal, temporal, parietal and cingulate sub-regions in which CBF and CVR were calculated. The depressed group exhibited an anterior-posterior gradient in CBF, with lower CBF throughout the frontal lobe but higher CBF in the parietal lobe, temporal lobe, thalamus and hippocampus. A similar anterior to posterior gradient was observed in the cingulate cortex, with anterior regions exhibiting lower CBF and posterior regions exhibiting higher CBF. We did not observe any group differences in CVR measures. We did not observe significant relationships between CBF and CVR with vascular risk or WMH volumes, aside from an isolated finding associating higher WMH volumes with lower CBF in the rostral anterior cingulate cortex. Decreased anterior CBF in depressed elders might reflect decreased metabolic activity in these regions, while increased posterior CBF may represent either compensatory processes or different activity of posterior intrinsic functional networks. Future work should examine how these findings are related to compensatory changes with aging.

Frontocingulate cerebral blood flow and cerebrovascular reactivity associated with antidepressant response in late-life depression.

BACKGROUND: Vascular pathology is common in late-life depression (LLD) and may contribute to alterations in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). In turn, such hemodynamic deficits may adversely affect brain function and clinical course. The goal of this study was to examine whether altered cerebral hemodynamics in depressed elders predicted antidepressant response. METHODS: 21 depressed elders completed cranial 3T MRI, including a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition on both room air and during a hypercapnia challenge. Participants then completed 12 weeks of open-label sertraline. Statistical analyses examined the relationship between regional normalized CBF and CVR values and change in Montgomery-Asberg Depression Rating Scale (MADRS) and tested for differences based on remission status. RESULTS: 10 participants remitted and 11 did not. After controlling for age and baseline MADRS, greater change in MADRS with treatment was associated with lower pre-treatment normalized CBF in the caudal anterior cingulate cortex (cACC) and lateral orbitofrontal cortex (OFC), as well as lower CVR with hypercapnia in the caudal medial frontal gyrus (cMFG). After controlling for age and baseline MADRS score, remitters exhibited lower CBF in the cACC and lower CVR in the cMFG. LIMITATIONS: Our sample was small, did not include a placebo arm, and we examined only specific regions of interest. CONCLUSIONS: Our findings suggest that increased perfusion of the OFC and the ACC is associated with a poor antidepressant response. They do not support that vascular pathology as measured by CBF and CVR negatively affects acute treatment outcomes.

Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis.

INTRODUCTION: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common. AREAS COVERED: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 - 1.10) and frequency of ≥ 1 AE (RR = 1.19, 95% CI = 0.95 - 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, ≥ 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs. EXPERT OPINION: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed.