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ACNP 57Th Annual Meeting: Poster Session I www.nature.com/npp ABSTRACTS COLLECTION ACNP 57th Annual Meeting: Poster Session I 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. https://doi.org/10.1038/s41386-018-0266-7 M1. Lifespan Effects of Early Life Stress on Aging-Related Conclusions: These findings suggest a role for ELA in the form Trajectory of Memory Decline of poor maternal care in increasing the likelihood to development of peripheral IR, altered central glucocorticoid function and Benedetta Bigio*, Danielle Zelli, Timothy Lau, Paolo de Angelis, corresponding anxiety states in adulthood, and that these factors Daniella Miller, Jonathan Lai, Anisha Kalidindi, Susan Harvey, Anjali may encode lifelong susceptibility to pathophysiological aging. Ferris, Aleksander Mathe, Francis Lee, Natalie Rasgon, Bruce McEwen, Given our earlier reported association between IR and a LAC Carla Nasca deficiency, a candidate biomarker of major depression that is a risk factor for aging-associated memory decline, we are currently Rockefeller University, New York, New York, United States assessing LAC levels in this mechanistic framework. This model may provide endpoints for identification of early windows of opportunities for preemptive tailored interventions. Background: Early life adversities (ELA), such as variations in Keywords: Early Life Adversity, Glucocorticoids, Insulin Resis- maternal care of offspring, are critical factors underlying the tance, Glutamate, Memory Function individual likelihood to development of multiple psychiatric and Disclosure: Nothing to disclose. medical disorders. For example, our new translation findings suggest a role of ELA in the form of childhood trauma on fi development of metabolic dysfunction, such as a de ciency in M2. Genetic Signatures of Response to Combination acetyl-L-carnitine (LAC) and insulin resistance (IR), in patients Escitalopram-Memantine Treatment for Geriatric Depression: with major depression (MDD). Arising from the postulate of A Randomized, Double-Blinded, Placebo-Controlled Pilot insulin resistance (IR) as a pathophysiological link in diabetes, Study depression and dementia (“the 3 D’s”), we implemented a mating rodent model with high and low nurturing dams to study the lifespan effects of ELA on peripheral metabolic Adrienne Grzenda*, Helen Lavretsky, Prabha Siddarth, Natalie St. Cyr physiology, central glucocorticoid function and behavioral states. UCLA, Los Angeles, California, United States Methods: We devised a computerized setup to record and assess the maternal care provided by wild-type or heterozygous Background: Geriatric depression is frequently associated with BDNF val66met (hets) dams on offspring which were screened for mild cognitive impairment (MCI), which responds poorly to individual anxiety-like behavior at the light dark, peripheral antidepressant monotherapy. Furthermore, comorbid depression markers of IR and central glucocorticoid function in adulthood, in patients with cognitive impairment appears to accelerate the and subsequently assessed for memory function in later age. neurodegenerative process, accelerating conversation to demen- Maternal care was assessed on the basis of previously employed tia. Our objective was to evaluate the efficacy of memantine ethological parameters by analyzing in and out of the nest caring augmentation of escitalopram treatment in elderly patients in and self-maintenance behaviors. Behavioral and molecular ana- improving clinical and cognitive outcome. Determine if unique lyses in adulthood and midlife mice were performed as previously gene signatures underlie escitalopram-memantine treatment described by four observers who were blind to the sample response compared to escitalopram alone. conditions. Two-tailed t-tests and multiple regression were used as Methods: We conducted a 12-month double-blinded, placebo- appropriate to specific analyses. controlled trial in older adults to assess the efficacy of combina- Results: We find that offspring receiving low quality maternal tion memantine and escitalopram therapy compared to escitalo- care in the early life show peripheral IR in adulthood as suggested pram and placebo for the treatment of depression (ClinicalTrials. by increased levels of insulin, glucose and tryglicerides in gov NCT01902004). For the current study, we analyzed the first 37 comparison with offspring that received high quality maternal participants to completed 6-month follow up. The primary care. This state of IR in adulthood is concomitant with increased outcome was remission of depressive symptoms, defined as expression of the mineralocorticoid receptors (MR) in hippocam- Hamilton Depression Rating Scale (HAM-D) scores of 6 or less for 3 pus and corresponding anxiety-like behavior at the light-dark test consecutive weeks following initiation of treatment. Secondary in low nurtured offspring. Furthermore, low nurtured mice showed measures included apathy, quality of life, and cognition. Genome- cognitive impairments in contextual memory at the Y maze in wide transcriptional profiles were generated from peripheral midlife, suggesting dementia-like symptoms, which were not blood leukocytes sampled at baseline and 3 months following apparent before. initiation of treatment. ACNP 57th Annual Meeting: Poster Session I S78 Results: Escitalopram daily doses ranged between 10-20 mg; Methods: Online high frequency rTMS was applied over the left memantine daily doses ranged between 10-20 mg. Both treat- DLPFC to test the hypothesis that active rTMS would lead to ment groups demonstrated similar remission rates at 6-month significant improvements in memory recall accuracy compared to follow-up with significant improvement in depression, anxiety, sham stimulation, and that these effects would be most and overall clinical illness severity. Escitalopram with memantine pronounced in WM manipulation conditions with the highest treatment resulted in additional improvements in apathy, quality cognitive demand in both young and older healthy adults. rTMS of life, and intermediate/delayed memory. There exists unique was applied while participants performed a delayed response baseline and post-treatment gene signatures that predicted alphabetization task with three individually-titrated levels of response to combination escitalopram-memantine compared to difficulty. The TMS coil placement was optimized by integrating escitalopram-placebo treatment. Furthermore, bioinformatics ana- electric field modeling with individualized functional magnetic lysis of differentially expressed gene targets indicates unique and resonance imaging activation maps in left DLPFC based on the synergistic mechanisms of action mediating antidepressant WM task and was implemented during the experiment using response in monotherapy and memantine augmentation. stereotactic neuronavigation with real-time robotic guidance, Conclusions: Pilot data indicate that memantine augmentation allowing accurate targeting during the stimulation. Participants of escitalopram treatment in geriatric depression results in an were scheduled for 6 sessions. The first visit consisted of enhanced clinical response profile, including improvements in consenting, exclusionary screening, resting motor threshold apathy, resilience, quality of life, and cognition. There was no (rMT) assessment and 6 blocks of practice with the behavioral difference in depression remission rates between the two groups. task. Participants then returned for an MRI visit and four more Remission of depression, however, was associated with unique rTMS sessions. On each rTMS visit, 25 pulses of 5 Hz rTMS were gene signatures in each treatment group, which may direct applied at rMT while subjects performed the WM task with the selection of patients to receive combination therapy in future titrated 3 difficulty levels (Easy, Medium, and Hard), with accuracy precision medicine initiatives. The current findings need to be feedback given at the end of each block. Ten blocks of the task replicated in a larger sample with additional time-course data to were performed: a first block without stimulation, four blocks of determine if additional differences exist between the treatments active or sham stimulation, one block without stimulation, and remission rate and overall degree of response. four more blocks with the sham or active stimulation. The order of Keywords: Geriatric Depression, Antidepressant Response, stimulation type (Active or Sham) was presented according to an Neuroprotection, Escitalopram, Memantine ABBA schedule 1234567890();,: Disclosure: Nothing to disclose. Results: Twenty-nine young adults (17 females and 12 males; 22.9 ± 4.8 years old) and eighteen older adults (13 females and 5 males; age: 69.7 ± 4.8 years old) completed the full protocol. A significant interaction between Difficulty Level and Stimulation M3. Online Repetitive Transcranial Magnetic Stimulation = Enhances Working Memory Performance in Younger and Type (Active or Sham rTMS) was found (F(2, 88) 8.49, p < .001). Older Adults The decomposition of this interaction with Bonferroni correction revealed a significant difference in the Hard condition, with active rTMS producing increased accuracy compared to sham rTMS (F Lysianne Beynel, Simon W. Davis, Susan Hilbig, Wesley Lim, Angel V. (1,44) = 17.15, p = .006). Investigating this effect in both young Peterchev, Roberto Cabeza, Greg Appelbaum, Sarah Lisanby,
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