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Dording, Christina

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Dording

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Christina

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Dording, Christina
Author's Publications: search.filters.isAuthorOfPublication.686d918f-20d5-48a4-853e-e8b64457fb63

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    Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women
    (Physicians Postgraduate Press, Inc, 2020-06-09) Dichtel, Laura; Nyer, Maren; Dording, Christina; Fisher, Lauren; Cusin, Cristina; Shapero, Benjamin; Pedrelli, Paola; Kimball, Allison; Rao, Elizabeth; Mischoulon, David; Fava, Maurizio; Miller, Karen K.
    Abstract Objective: The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of GABAA receptors and a putative treatment for mood disorders. We performed a pilot study to determine whether an oral allopregnanolone analog (ganaxolone) may be effective for treatment-resistant depression in postmenopausal women. Methods: Ten post-menopausal women (age 62.8±6.3 years, range 53-69) with treatment-resistant depression [current DSM-IV major depressive episode per the Structured Clinical Interview for DSM-IV (SCID), Montgomery-Asberg Depression Rating Scale (MADRS) 16, and treated with an adequately dosed antidepressant for ≥6 weeks] were studied from 12/2016 to 4/2018. Open-label ganaxolone (225 mg BID, increased to 450 mg BID if tolerated) was administered for 8 weeks, followed by a 2-week taper. Results: Mean total MADRS score (primary endpoint) decreased by 8 weeks [24.4±1.6 (SEM) to 12.8±2.9, p=0.015] and persisted over the two-week taper (p=0.019); 44% of subjects experienced response (score decrease ≥50%) and remission (final score <10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including the Inventory of Depressive Symptomatology-Self-Report (IDS-SR; p=0.003), MADRS Reduced Sleep subscale (p<0.001), Symptoms of Depression Questionnaire (SDQ) total score (p=0.012), and SDQ subscales for disruptions in sleep quality (p=0.003) and changes in appetite and weight (p=0.009) over 8 weeks. No significant effects were observed on quality-of-life or sexual function. All subjects experienced sleepiness and fatigue; 60% experienced dizziness. Conclusion: In this open-label, uncontrolled pilot study, ganaxolone appears to exert antidepressant effects but produces sedation with twice-daily dosing. Ganaxolone may also improve sleep, which may be useful in patients with depression and insomnia.
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    Factors Associated With New‐Onset Depression Following Ischemic Stroke: The Women's Health Initiative
    (John Wiley and Sons Inc., 2017) Salinas, Joel; Ray, Roberta M.; Nassir, Rami; Lakshminarayan, Kamakshi; Dording, Christina; Smoller, Jordan; Wassertheil‐Smoller, Sylvia; Rosand, Jonathan; Dunn, Erin; Rossouw, Jacques; Ludlam, Shari; Burwen, Dale; McGowan, Joan; Ford, Leslie; Geller, Nancy; Anderson, Garnet; Prentice, Ross; LaCroix, Andrea; Kooperberg, Charles; Manson, JoAnn E.; Howard, Barbara V.; Stefanick, Marcia L.; Jackson, Rebecca; Thomson, Cynthia A.; Wactawski‐Wende, Jean; Limacher, Marian; Wallace, Robert; Kuller, Lewis; Shumaker, Sally
    Background: Psychosocial characteristics have a strong effect on risk of depression, and their direct treatment with behavioral interventions reduces rates of depression. Because new‐onset poststroke depression (NPSD) is frequent, devastating, and often treatment‐resistant, novel preventive efforts are needed. As a first step toward developing behavioral interventions for NPSD, we investigated whether prestroke psychosocial factors influenced rates of NPSD in a manner similar to the general population. Methods and Results: Using the Women's Health Initiative, we analyzed 1424 respondents who were stroke‐free at enrollment and had no self‐reported history of depression from enrollment to their nonfatal ischemic stroke based on initiation of treatment for depression or the Burnam screening instrument for detecting depressive disorders. NPSD was assessed using the same method during the 5‐year poststroke period. Logistic regression provided odds ratios of NPSD controlling for multiple covariates. NPSD occurred in 21.4% (305/1424) of the analytic cohort and varied by stroke severity as measured by the Glasgow scale, ranging from 16.7% of those with good recovery to 31.6% of those severely disabled. Women with total anterior circulation infarction had the highest level (31.4%) of NPSD while those with lacunar infarction had the lowest (16.1%). Prestroke psychosocial measures had different associations with NPSD depending on functional recovery of the individual. Conclusions: There is a difference in the relationship of prestroke psychosocial status and risk of NPSD depending on stroke severity; thus it may be that the same preventive interventions might not work for all stroke patients. One size does not fit all.