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Neuropsychopharmacology Download Citation Sponsorship Statement: Publication of this supplement is sponsored by the ACNP. Individual contributor disclosures may be found within the abstracts. Asterisks in the author lists indicate presenter of the abstract at the annual meeting. Early life adversities ELAsuch as variations in maternal care of offspring, are critical factors underlying the individual likelihood to development of multiple psychiatric and medical disorders. For example, our new translation findings suggest a role of ELA in the form of childhood trauma on development of metabolic dysfunction, such as a deficiency in acetyl-L-carnitine LAC and Ame CU-98R Webcam resistance IRin patients with major depression MDD. We devised a computerized setup to record and assess the maternal care provided by wild-type or heterozygous BDNF val66met hets dams on offspring which were screened for individual anxiety-like behavior at the light dark, peripheral markers of IR and central glucocorticoid function in adulthood, and subsequently assessed for memory function in later age.
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Maternal care was assessed on the basis of previously employed ethological parameters by analyzing in and out of the nest caring and self-maintenance behaviors. Behavioral and molecular analyses in adulthood and midlife mice were performed as previously described by four observers who were blind Ame CU-98R Webcam the sample conditions. Two-tailed t-tests and multiple regression were used as appropriate to specific analyses.
We find that offspring receiving low quality maternal care in the Ame CU-98R Webcam life show peripheral IR in Ame CU-98R Webcam as suggested by increased levels of insulin, glucose and tryglicerides in comparison with offspring that received high quality maternal care. This state of IR in adulthood is concomitant with increased expression of the mineralocorticoid receptors MR in hippocampus and corresponding anxiety-like behavior at the light-dark test in low nurtured offspring.
Furthermore, low nurtured mice showed cognitive Ame CU-98R Webcam in contextual memory at the Y maze in midlife, suggesting dementia-like symptoms, which were not apparent before. These findings suggest a role for ELA in the form of poor maternal care in increasing the likelihood to development of peripheral IR, altered central glucocorticoid function and corresponding anxiety states in adulthood, and that these factors may encode lifelong susceptibility to pathophysiological aging. Given our earlier reported association between IR and a LAC deficiency, a candidate biomarker of major depression that is a risk factor for aging-associated memory decline, we are currently assessing LAC levels in this mechanistic framework. This model may provide endpoints for identification of early windows of opportunities for preemptive tailored interventions.
Nothing to disclose. Geriatric depression is frequently associated Ame CU-98R Webcam mild cognitive impairment MCIwhich responds poorly to antidepressant monotherapy. Furthermore, comorbid depression in patients with cognitive impairment appears to accelerate the neurodegenerative process, accelerating conversation to dementia. Our objective was to evaluate the efficacy of memantine augmentation of escitalopram treatment in elderly patients in improving clinical and cognitive outcome.
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Determine if unique gene signatures underlie escitalopram-memantine treatment response compared to escitalopram alone. We conducted a month double-blinded, placebo-controlled trial in older adults to assess the efficacy of combination memantine and escitalopram therapy compared to escitalopram and placebo for the treatment of depression ClinicalTrials. For the current study, we analyzed the first 37 participants Ame CU-98R Webcam completed 6-month follow up. The primary outcome was remission of depressive symptoms, defined as Hamilton Depression Rating Scale HAM-D scores of Ame CU-98R Webcam or less for 3 consecutive weeks following initiation of treatment.
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Secondary measures Ame CU-98R Webcam apathy, quality of Ame CU-98R Webcam, and cognition. Genome-wide transcriptional profiles were generated from peripheral blood leukocytes sampled at baseline and 3 months following initiation of treatment. Escitalopram daily doses ranged between mg; memantine daily doses ranged between mg. Both treatment groups demonstrated similar remission rates at 6-month follow-up with significant improvement in depression, anxiety, and overall clinical illness severity. There exists unique baseline and post-treatment gene signatures that predicted response to combination escitalopram-memantine compared to escitalopram-placebo treatment.
Furthermore, bioinformatics analysis of differentially expressed gene targets indicates unique and synergistic mechanisms of action mediating antidepressant response in monotherapy and memantine augmentation. Pilot data indicate that memantine augmentation of escitalopram treatment in geriatric depression results in an enhanced clinical response profile, including improvements in apathy, resilience, quality of life, and Ame CU-98R Webcam. There was no difference in depression remission rates between the two groups.
Ame CU-98R Webcam of depression, however, was associated with unique gene signatures in each treatment group, which may direct selection of patients to receive combination therapy in future precision medicine Ame CU-98R Webcam. The current findings need to be replicated in a larger sample with additional time-course data to determine if additional differences exist between the treatments remission rate and overall degree of response.
Working memory WM is the ability to perform mental operations on information that is stored in a Ame CU-98R Webcam, limited capacity buffer. Through the interface between long-term memories and moment-to-moment information available in the environment, WM allows humans to carry out successful goal-directed behaviors. As such, WM is widely involved in the achievement of complex tasks such as learning, Ame CU-98R Webcam making, and reasoning.