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ACNP 56Th Annual Meeting: Poster Session II, December 5, 2017 Neuropsychopharmacology (2017) 42, S294–S475 © 2017 American College of Neuropsychopharmacology. All rights reserved 0893-133X/17 www.neuropsychopharmacology.org Poster Session II analyses revealed that the SASP index was positively correlated Palm Springs, California, December 3-7, 2017 with age (r = 0.2, p = 0.03) and CIRS score (r = 0.27, p = 0.005), and negatively correlated with information processing speed Sponsorship Statement: Publication of this supplement is (r = − 0.34, p = 0.001), executive function (r = − 0.27, p = 0.004) sponsored by the ACNP. and global cognitive performance (r = − 0.28, p = 0.007). Individual contributor disclosures may be found within the Conclusions: this is the first study to show that a set of abstracts. Part 1: All Financial Involvement with a pharma- proteins (i.e., SASP index) primarily associated with cellular ceutical or biotechnology company, a company providing aging is abnormally regulated and elevated in LLD. These clinical assessment, scientific, or medical products or compa- results suggest that individuals with LLD display enhanced nies doing business with or proposing to do business with aging related molecular patterns that are associated with ACNP over past 2 years (Calendar Years 2014–Present); Part higher medical comorbidity and worse cognitive function. 2: Income Sources & Equity of $10,000 per year or greater Finally, we provide a set of proteins that can serve as (Calendar Years 2014 - Present): List those financial relation- potential therapeutic targets and biomarkers to monitor the ships which are listed in part one and have a value greater than effects of therapeutic or preventative interventions in LLD. $10,000 per year, OR financial holdings that are listed in part Keywords: Late-Life Depression, Aging, Biomarkers one and have a value of $10,000 or greater as of the date of Disclosure: Nothing to Disclose. disclosure; Part 3: Financial Involvement with a pharmaceu- tical or biotechnology company, a company providing clinical assessment, scientific, or medical products or companies doing T2. Postpartum Effects on the Dopamine System of business with or proposing to do business with ACNP which Female Rats constitutes more than 5% of personal income (Calendar Years 2014 - Present); Part 4: Grants from pharmaceutical or Millie Rincón-Cortés*, Anthony Grace biotechnology company, a company providing clinical assess- University of Pittsburgh, Pittsburgh, Pennsylvania, ment, scientific, or medical products directly, or indirectly United States through a foundation, university, or any other organization (Calendar Years 2014 - Present); Part 5: My primary employer Background: The period after childbirth (i.e. postpartum is a pharmaceutical/biotech/medical device company. period) is a time of elevated risk for the development of Asterisks in the author lists indicate presenter of the abstract affective disorders (Stowe and Nemeroff, 1995). Indeed, the at the annual meeting. highest rates of anxiety and depression occur during the first few weeks, months or year postpartum compared with other times in a woman’s life (Pawluski et. al 2017). In accordance, T1. The Senescent-Associated Secretory Phenotype: A animal models of postpartum depression have also reported Marker of Enhanced Molecular Senescence Changes in time-dependent effects on depressive-like behavior and Late-Life Depression anhedonia (Brummelte and Galea, 2010). In rodents, parity Breno Diniz*, Charles Reynolds, Etienne Sibille, (i.e. the condition of having borne offspring) induces Meryl Butters changes in DA-mediated behavioral responses, which may reflect some influence on DA neurotransmission (Hucke et. University of Texas Health Science Center at Houston, al, 2001). However, the neurobiological underpinnings of this Houston, Texas, United States increased female susceptibility to depression during the postpartum period remain poorly understood. Background: Late-Life Depression (LLD) is common and The dopamine (DA) system has traditionally been associated associated with higher risk of age-related negative health with anhedonia, the inability to derive pleasure from outcomes. The mechanisms of this association are not clear, normally rewarding stimuli, and has been repeatedly but may involve the activation of biological pathways related implicated in the pathophysiology in depression. A causal to senescence. This study aims to investigate whether a link between a hypofunctioning DA system (i.e. decreased systemic molecular pattern associated with aging (senescent- DA neuron activity) and stress-induced depression-related associated secretory phenotype [SASP]) is elevated in adults behaviors (i.e. anhedonia, despair, anxiety) has been with late-life depression (LLD), compared with never- demonstrated in animal models (Tye et. al, 2013; Chang depressed elderly comparison participants. and Grace, 2014), with females showing greater effects Methods: We included 111 older adults (80 with LLD and 31 (Rincón-Cortés and Grace, 2017). Surprisingly, little is comparison participants) in this study. A panel of 22 SASP- known about DA system function in females following related proteins was extracted from a previous multiplex reproductive experience, including parity (i.e. the condition protein panel performed in these participants. We conducted of having borne offspring). To this end, we assessed anxiety- a principal component analysis to create the SASP index like behavior, social motivation and DA system function in based on individual weights of each of protein. virgin and during the early postpartum period in females. Results: LLD showed a significantly higher SASP index Methods: Virgin and early postpartum (i.e. 1 day post- compared with comparison participants, after controlling for partum, 3 days postpartum) female rats were tested for potential confounders (F(1,98) = 7.3, p = 0.008). Correlation anxiety-like behavior in the elevated plus maze (EPM) and ACNP 56th Annual Meeting Abstracts S295 social motivation in the social approach test (SAT). Single- the mPFC, including the ventral mPFC. tDCS is followed by unit recordings of VTA DA neurons were conducted the day five 10-minute trials of individualized ERP to test the following behavioral testing and 3 parameters were mea- acquisition of therapeutic extinction learning. Subjects return sured: i) the number of spontaneously active DA cells (i.e. 24 hours later to complete five additional exposure trials to population activity), ii) basal firing rate and iii) firing pattern test the recall of therapeutic learning. Subjective units of (i.e. the percentage of spikes firing in bursts). distress (SUDS) are assessed every minute before, during, Results: Postpartum female rats exhibited a reduction in the and after the exposure task. percentage of open arm entries (p o0.01) and the percentage Results: tDCS had no significant effects on pre-exposure of time spent in the open arms (p o0.05) of the EPM (but post-tDCS) SUDS levels and did not affect SUDS ratings compared with virgin female rats at 1-day post-partum. during the first minute of the first exposure trials (ps 4 .05), Postpartum female rats tested at both time points (1-day, 3- suggesting it did not have a non-specific anxiolytic effect. days) exhibited reduced social motivation (p o0.001), as However, data suggest that tDCS significantly enhanced indexed by less sniff time of a younger, same-sex animal in acquisition of therapeutic extinction learning. Mixed ANO- the SAT. Postpartum females exhibited an attenuation of DA VA showed that, over the course of the five exposure trials population activity, as indexed by a reduction in the number on day 1 of the ERP challenge, subjects who received active- of cells per electrode track in the VTA, compared with virgin tDCS reported greater SUDS reductions than subjects who rats (po0.001) but no differences in firing rate (p = 0.42) or receive sham tDCS, F (1.99, 27.79) = 3.90, p o .05, η2p = the percentage of spikes occurring in bursts (p = 0.53). .22. Said otherwise, subjects in the active tDCS condition Conclusions: Collectively, our findings suggest that parity reported 67.94% reductions SUDS whereas subjects who can drive changes in affective behavior (i.e. increases anxiety- received sham tDCS reported 18.34% reductions in SUDS, F like behavior and reduces social motivation during the early (1, 14) = 13.04, p o .01, d = 1.93. Exploratory mixed postpartum period and that these behavioral changes are ANOVAs suggest that active tDCS had a minimal effect on associated with an attenuation of DA activity within this early phase extinction learning (average SUDS change across period. trials 1 to 2), F (1, 6) = .65, p = .45, but had a significant Keywords: Anxiety, Social Behavior, Postpartum Depression, effect on late phase extinction learning (trials 4 to 5), F (1, 6) Dopamine, Electrophysiology = 11.34, p = .02. Contrary to our prediction, tDCS did not Disclosure: Nothing to Disclose. appear to affect extinction recall. In fact, subjects who received active tDCS evinced marginally poorer recall compared to subjects who received sham tDCS, F (1, 14) T3. Multifocal Transcranial Direct Current Stimulation = 3.63, p = .08, η2p = 21. Targeting the Medial Prefrontal Cortex Improves Conclusions: Our findings suggest that multifocal tDCS Exposure-Relevant Learning Among Obsessive- targeting the mPFC prior to individualized exposure can Compulsive Disorder Patients improve acquisition of therapeutic extinction learning Thomas Adams*, Benjamin Kelmendi, Jamilah George,
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