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Abstracts | 37
clinicians to better understand and choose better treatment
options for these populations.
Keywords: Nicotinic antagonist, treatment resistance, major
depressive disorder.
Bone density, muscle mass and body fat in elderly
women with depression
Adam Wysokinski
Medical University of Lodz, Poland
Introduction: Osteoporosis is a pathological condition of
reduced bone mineral density, leading to increased risk of bone
fractures. Studies show there is an association between depression and increased risk of osteoporosis and bone fractures. The
risk is even higher in postmenopausal women with depression. The aim of this study was to evaluate association between
bone density, muscle mass and body fat in elderly women with
Methods: 29 elderly (age ≥60 years) European Caucasian
women with unipolar depression and 37 non-depressed elderly
European Caucasian women were included into the study. All
women were post menopause. Body composition was measured using two methods: bioimpedance analysis (BIA) and dualenergy X-ray absorptiometry (DXA). We measured bone mineral
content (BMC) and bone mineral density (BMD) over the lumbar spine while performing body composition analysis with the
DXA method.
Results: Mean total body BMC, spine BMD and T-score in the
study groups were comparable. Six subjects were determined
to be osteopenic (16.2% in the control group and 20.7% in the
depression group), while osteoporosis was found in 4 patients
with depression (13.8%) and in two healthy controls (5.41%);
both differences are not significant. We found a significant
association between depression severity and bone parameters
(BMC: r = 0.46, p = 0.016; BMD: r = 0.40, p = 0.03; T-score: r = 0.37,
p = 0.047). Also, we found several (mostly positive) correlations
between muscle mass or body fat and bone parameters.
Conclusion: In elderly women depression may not be associated with recued bone parameters and may not affect the risk
of osteoporosis or bone fractures. Metabolic parameters may
affect bone parameters and should be monitored in patients
with depression.
Characteristics of escitalopram discontinuation
Norio Yasui-Furukori, Kojiro Hashimoto, Masamichi Ishioka, Kazuhiko
Nakamura, Norio Suguwara, Tetsu Tomita, Shoko Tsuchimine
Hirosaki University, Japan
Background: Antidepressant discontinuation syndrome (ADS)
occurs frequently in patients undergoing an abrupt discontinuation of their antidepressant medication.
Methods: We evaluated 25 consecutive outpatients with depression who discontinued escitalopram. The presence of ADS was
evaluated according to the Anti-Depressants Discontinuation
Syndrome (ADDS) checklist.
Results: ADS was observed in 14 of the 25 patients. Frequent
symptoms were dizziness (44%), muscle tension (44%), chills
(44%), confusion or trouble concentrating (40%), amnesia
(28%) and crying (28%). The treatment doses and plasma
concentrations of escitalopram were significantly higher in
patients with ADS compared to patients without ADS. No group
differences were observed regarding age, sex or duration of escitalopram treatment prior to the discontinuation.
Conclusion: These findings suggest that a higher dose and lower
clearance of escitalopram lead to a higher risk of ADS. Very slow
tapering is recommended for all patients.
The antidepressant-like effect induced by caloric
restriction: possible involvement of orexin-A.
Stanquini, LA1; Ribeiro, DE1; Scopinho, AA1; Joca, SRL2. 1FMRP-USP,
FCFRP-USP; Ribeirão Preto-SP, Brasil.
effect, BDNF
Introduction: Evidence suggests that rats and mice submitted
to caloric restriction perform better on learning and memory
tests and show behavioral adaptation in animal models of
depression. These effects may involve changes in neurotransmitters and neuropeptides important for modulating stress
responses, like orexin A (OXA) and brain-derived neurotrophic
factor (BDNF). OXA, a neuropeptide produced by neurons in the
lateral hypothalamic and perifornical areas. OXA modulates
the release of BDNF, a highly expressed neurotrophin, which
mediates antidepressant-like effects through interaction with
TrkB receptors. Our work tested the hypothesis that CR-induced
behavioral effects would involve OXA and BDNF signaling.
Methods: BALB/c mice were submiited to CR for 10 days (receiving 60% of the total energy supply based on the control animals)
and exposed to forced swimming test (FST). Independent groups
were pretreated with K252 (TrkB receptor antagonist; 80ug/kg,
ip), SB-334867 (orexin-1 receptor antagonist, 10mg/kg,ip) or
vehicle on days 1, 5 and 9 of CR, and were submitted to FST on
the 10th day.
Results: CR induced an antidepressant-like effect when compared with ad libitum condition (Two-way ANOVA interaction:
F1,19=5.287; t test, p<0,005) and this effect was reversed by the
pre-treatment with SB-334867 (test t, p>0,005). CR effect was
reproduced in the group treated with SB-334867 (two-way
ANOVA interaction: F1,26=45.01test t, p<0,005), but this effect
was not reversed by the pre-treatment with SB-334867 (test t,
Conclusion: CR is able to promote antidepressant-like effect,
possibly via OXA-OX1R signalling.
Financial support: FAPESP, CNPq, FAEPA and CAPES.
Reversal of stress-induced anhedonia by the multimodel antidepressant, vortioxetine
AK Christensen1, O Wiborg1, HK Müller1
Translational Neuropsychiatry Unit, Department of Clinical Medicine,
Aarhus University Hospital, Skovagervej 2, 8240 Risskov, Denmark.
Vortioxetine, a newly approved antidepressant for the treatment
of major depressive disorder has received special attention for
its combination of antidepressant and pro-cognitive properties.
Vortioxetine is a multimodal drug with a pharmacological profile distinct from conventional SSRIs as it works through two
complementary mechanisms: 5-HT receptor activity modulation and SERT reuptake inhibition. Previous gene expression
studies have suggested that vortioxetine has neuroplasticity
38 | International Journal of Neuropsychopharmacology, 2016
enhancing properties; however, most of these studies were conducted in naïve animals.
Chronic mild stress (CMS) has been reported to induce an
anhedonic-like state in rodents that resembles some of the
symptoms of human depression. In the present study we use
the CMS model to investigate molecular correlates of possible
anti-anhedonic and cognitive enhancing effects of vortioxetine.
Adult male Long Evans rats were exposed to 9 weeks of CMS,
and treated with vortioxetine (administered in the diet) during
the last 4 weeks of the stress period. Sucrose consumption tests
were performed weekly during the stress and treatment periods to evaluate the anhedonic state. Cognitive functions were
assessed by the social interaction and Barnes maze tests.
Our preliminary data show that the CMS paradigm reduced
the sucrose consumption in a subset of the rats, indicating
anhedonic-like behavior, while another subgroup of rats were
resilient to the CMS. The anhedonic-like state was reversed
in 70 percent of the animals in response to chronic vortioxetine treatment, while the remaining animals were resistant
(non-responder rats).
To improve our understanding of the molecular mechanisms
associated with the anti-anhedonic effect of vortioxetine, we
are currently investigating synaptosomes prepared from the
hippocampus and prefrontal cortex for synaptic alterations in
proteins involved in neuroplasticity with particular focus on
proteins regulating dendritic spine function and morphology.
A comparative study of fluoxetine and ketamine on
quinolinic acid: An in vivo study in rats
Amanda Eskelund1, David P Budac2, Connie Sanchez1,2, Betina
Elfving1, Gregers Wegener1
Translational Neuropsychiatry Unit, Aarhus University, Risskov,
Denmark. 2Lundbeck Research US, Paramus, NJ, USA.
Background: The pathophysiology underlying major depressive
disorder (MDD) remains to a large extent enigmatic. Stress and
inflammatory processes can induce MDD and push tryptophan
through the kynurenine pathway. This may ultimately result
in increased quinolinic acid (QUIN), a neurotoxic metabolite
of kynurenine with (N-methyl-D-aspartate receptor (NMDA-R)
agonistic properties that has been associated with depressive symptoms1 and suicide2. Sharing a common precursor,
these processes may converge with the predominant serotonin
hypothesis of MDD. Aim: To investigate the effects of the selective serotonin reuptake inhibitor fluoxetine or the NMDA-R
antagonist ketamine on QUIN levels in both brain and plasma in
three different rat strains.
Method: The genetic rat model of depression, Flinders Sensitive
Line rat and its controls: Flinders Resistant Line and Sprague
Dawley rats were used. Male rats aged 9–12 weeks were treated
with fluoxetine (160 mg/L drinking water) or ketamine (15 mg/kg,
i.p., every 3rd day, which produces a sustained antidepressantlike effect in the forced swim test), or 0.9% saline (vehicle, i.p.
every 3rd day) for 14 days. Subsequently, QUIN levels in 8 different brain regions (right and left frontal cortex, hippocampus, hypothalamus, striatum, midbrain, cerebellum, “rest of
brain”) and plasma were measured by liquid-chromatography/
Results: Fluoxetine significantly decreased QUIN in midbrain,
cerebellum and rest of brain (by 18–35%) and plasma (29%).
There was no effect of ketamine in any brain area or plasma.
Conclusion: At clinically relevant levels of SERT occupancy
fluoxetine produce a reduction of the neurotoxic QUIN, whereas
ketamine had no effects using an intermittent dosing regimen.
1. Raison et al. Mol. Psychiatr. 2010; 15: 393–403.
2. Erhardt et al. Neuropsychopharmacology 2013; 38: 743–752
Changes of serotonergic functions are mediated
via metabolic control of serotonin transporter in
stressed mice
Takahiro Ito1, Hirotake Hida1, Fumiya Yamamoto1, Sho Hasegawa1,
Akihiro Mouri1, Norio Ozaki2, Yukihiro Noda1, 2
Division of Clinical Sciences and Neuropsychopharmacology, Faculty
and Graduate School of Pharmacy, Meijo University, Nagoya, Japan
Department of Psychiatry, Nagoya University Graduate School of
Medicine, Nagoya, Japan
Objective: Many kinds of antidepressants, such as tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs)
have been developed, whereas approximately 30 % of patients
with major depressive disorder are “treatment-resistant depression”, which is resistant to existing antidepressants. SSRIs are
the first-line antidepressants in the treatment of major depressive disorder, and directly bind to the serotonin transporter
(SERT). SERT activity is attenuated by PKC, which induced SERT
phosphorylation and surface expression, thereby SERT is a key
regulator of SERT-serotonergic functions. The present study was
investigated whether PKC is related to depressive behaviors in
the forced swimming-stressed mice, and further they are mediated via SERT function in stressed mice.
Method: Mice were forced to swim (the 1st swimming: stressed
mice) to get the immobility time stable at the 2nd swimming.
On the next day, they were forced to swim again (the 2nd swimming: tested mice), and 20 min later, they were performed the
social interaction test. The effects of phorbol 12-myristate
13-acetate (PMA: a PKC activator), imipramine or sertraline (an
antidepressant), and chelerythrine (a PKC inhibitor) on the performance of behavioral tests were examined, and PKC activity
and SERT expression were analyzed.
Result: The expression levels of phosphorylated SERT protein
were decreased in tested mice. PMA as well as antidepressants
attenuated the immobility and deficits of social behaviors in
tested mice. It also increased in the expression levels of phosphorylated PKC and SERT proteins. Chelerythrine exacerbated
both behavioral abnormalities in tested mice and decreased the
expression levels of phosphorylated PKC protein.
Conclusion: These results suggest that the PKC activator attenuates some depressive behaviors in stressed mice to promote
metabolism of SERT via phosphorylation PKC, and it might be a
novel antidepressant.
Neuroendocrine and behavioural changes in adult
offspring of dams treated with venlafaxine during
gravidity and lactation
Jezova D.1 Császár E.2, Melicherčíková K.,2, Ujhazy E.2, Mach M.2,
Zilava L.1, Garafová A.3, Dubovický M.2
Institute of Experimental Endocrinology, Biomedical Research Centre
and 2 Institute of Experimental Pharmacology and Toxicology, Slovak
Academy of Sciences, 3 Division of Neonatology of the University
Hospital and Slovak Medical University, Bratislava, Slovakia
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