Cerebral Small Vessel Disease and Depression Among Intracerebral Hemorrhage Survivors.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment. METHODS: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment. RESULTS: We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14-2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12-2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51-0.94]), and to benefit from antidepressant therapy (P=0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction P=0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH. CONCLUSIONS: CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.

Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E (APOE) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. METHODS: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE-MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. RESULTS: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P<0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P=0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. CONCLUSIONS: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE-MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

Mental Health Disparities Among Sexual and Gender Minority Frontline Health Care Workers During the Height of the COVID-19 Pandemic.

Purpose: This study measured mental health disparities in a Bronx, New York sample of frontline health care workers collected May-July, 2020, during the first wave of the COVID-19 pandemic. Methods: Using survey data (N = 741), we compared demographics, COVID-19 stressors, and adverse mental health outcomes between sexual and gender minority (SGM, n = 102) and non-SGM (n = 639) health care workers through chi-square/Kruskal-Wallis tests, crude/adjusted odds, and prevalence ratios. Results: SGM frontline health care workers had significantly higher depression, anxiety, impact of COVID-19, and psychological distress. Income (lower), age (younger), and COVID-19 stressors accelerated differences. Conclusion: Health care systems should support SGM frontline health care workers through affirming trauma-informed programming.

Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence.

OBJECTIVE: Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk. METHODS: We analyzed data from the Massachusetts General Hospital ICH study (n = 593) and the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n = 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk. RESULTS: We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p = 0.011) and HTNA burden (p = 0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed-etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05). CONCLUSIONS: We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial/ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity and investigating social determinants of health.

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity.

IMPORTANCE: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms. OBJECTIVE: To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke. MAIN OUTCOMES AND MEASURES: We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity. RESULTS: Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors. CONCLUSIONS AND RELEVANCE: Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

APOE genotype, hypertension severity and outcomes after intracerebral haemorrhage.

Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P < 0.05). APOE ε4 and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction P < 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120-129 mmHg and diastolic blood pressure <80 mmHg) only those with one or more APOE ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17-3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) APOE genotype also stratified risk for all small vessel disease outcomes. In conclusion, APOE genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.