S330
Abstracts
J.M. Le Melledo ∗
ifiable CV risk factors which have been shown to be associated with decreased blood plasma NOx levels. The decrease
in L-arginine levels in MD patients is a possible explanation
for the decrease in NO metabolites and platelet eNOS activity observed in MD patients. The decrease in L-citrulline levels is also consistent with the suggested decreased endothelial NO production. It remains to be determined whether
therapeutic normalization of the L-arginine levels in MD patients would normalize NO endothelial production and ultimately help improve the increased CV risk observed in MD
patients.
University Of Alberta, Psychiatry, edmonton, Canada
References
Introduction: Physically healthy patients suffering from major depression (MD) have been found to be at increased risk
of developing cardiovascular disease (CVD) independent of
conventional CVD risk factors. However, the exact mechanisms leading to increased CVD risk in MD patients remain
unknown. It has been suggested that decreased production
by the endothelium of the gas nitic oxide (NO) may contribute to the consistently observed increased risk of developing CVD in physically healthy patients suffering from
MD. NO is a gas synthesized from L-arginine (a conditionally
essential amino acid) and oxygen by endothelial nitric oxide
synthase (eNOS). The end products of NO production include
both NO and L-citrulline. NO is rapidly reduced to anions nitrite and nitrate, classically referred to as NO metabolites.
We and others have replicated findings of decreased levels
of NO metabolites (a surrogate measurement for endothelial NO production) in the serum of MD patients [1,2]. We
have also shown decreased platelet eNOS activity in MD patients [3]. The mechanism of this decreased production of
NO by the endothelium of MD patients has not yet been elucidated.
Aim of the study: To show that L-arginine plasma levels are
decreased in MD patients
Methods: Serum levels of L-arginine and L-citrulline were
measured using a Biochrom 30 amino acid analyser in 35
unmedicated physically healthy MD patients and 36 healthy
controls (HCs). Analyses were conducted using two-tailed
independent t-tests for each factor. A p-value of less than
0.05 was considered statistically significant for all statistical
tests.
Results: L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls
(73.54 + 21.53 umol/L and 84.89 + 25.16, p = 0.04 and
31.58 + 6.05 umol/L and 35.19 + 6.85 umol/L, p = 0.03 respectively). Age, body mass index (BMI), lipid and triglyceride levels, fasting glucose levels, systolic blood pressure,
physical activity, and average metabolism (as measured by
kcal/day consumed) were not significantly different between MD patients and HCs. A statistically but non clinically
significant difference was observed for diastolic blood pressure.
Conclusions: To the best of our knowledge, our study is the
first investigation to show decreased l-arginine serum levels in a large sample of unmedicated patients meeting diagnostic criteria for MD according to a validated structured
interview. A strength of our study is that we have controlled
(through both exclusion criteria and verifying a lack of difference between groups) for many non-modifiable and mod-
[1] Chrapko, W., Jurasz, P., Radomski, M.W., Lara, N., Archer, S.L.,
Le Melledo, J.M., 2004. Decreased platelet nitric oxide synthase
activity and plasma nitric oxide metabolites in major depressive
disorder. Biol Psychiatry 56, 129–134.
[2] Selley, M.L., 2004. Increased (E)-4-hydroxy-2-nonenal and
asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major
depression. J Affect Disord 80, 249–256.
[3] Chrapko, W., Jurasz, P., Radomski, M.W., Archer, S.L., Newman, S.C., Baker, G., Lara, N., Le Melledo, J.M., 2006. Alteration of decreased plasma NO metabolites and platelet NO synthase activity by paroxetine in depressed patients. Neuropsychopharmacology 31, 1286–1293.
tion in ischemic stroke. J Stroke Cerebrovasc Dis 18 (5), 354–
359.
doi: 10.1016/j.euroneuro.2018.11.516
P.501 Dysregulation of the nitric oxide pathway as a
risk factor for increased cardiovascular risk in patients
with major depression
doi: 10.1016/j.euroneuro.2018.11.517
P.502 Clinical audit: TAILOR - Target Antidepressant
Initiation choice to unLock positive patient Outcomes
and Response
J. Hopwood ∗
University of Melbourne, Professorial Psychiatry Unit, Melbourne, Australia
Background: Medication adherence is critical to the efficacy of antidepressant treatments in primary care [1]. Patient preferences and attitudes towards depression treatments influence adherence to antidepressant medication
(ADM).
Objective: The Target Antidepressant Initiation choice to
unLock positive patient Outcomes and Response (TAILOR)
was an online GP clinical audit to assist clinicians to tailor
the choice of ADM for the initial management of a patient
with depression by involving the patient in all management
decisions.
Methods: TAILOR commenced on March 2016 across GP clinics in Australia. Information on TAILOR was provided to clinics through various forums and clinicians could opt to participate as part of on-going education in mental health.
Each clinician who chose to participate in the program
were asked to identify 10 patients. To be eligible, patients
required diagnosis of a new episode of depression (first
episode or recurrence) and were not currently on ADM. Clinicians administered a 15-item patient questionnaire with
each patient, which included items on patient attitudes,
understanding of medication, expectations of response and
management plan.
Abstracts
Before selecting ADM, clinicians were reminded of the patient’s preferences and concerns. They were also provided
with information on specific antidepressant effects in areas
of importance to the patient from the 2015 Royal Australian
and New Zealand College of Psychiatry (RANZCP) Mood Disorders Guidelines [2].
A follow up questionnaire was sent 4 weeks later to participating GPs to evaluate how the audit affected their daily
practice, specifically the extent to which patient attitudes
were now considered in treatment management.
Results: One thousand eight hundred and seventy-three GPs
and 7,650 patients had participated in TAILOR at the end of
February 2018. Responses indicated that most patients felt
it was ‘important’ (49%) or ‘very important’ (49%) that their
GP discussed treatment preferences with them.
Over half the patients audited (53%) had concerns about
starting ADM treatment, with risk of side effects (77%) and
fear of becoming dependent (52%) being the main concerns.
By contrast, only 18% were concerned with no belief the
medication would work.
Most patients (60%) wanted to avoid weight gain, followed by sleep disturbance (52%), sexual dysfunction (43%),
discontinuation symptoms (37%), lack of interest and pleasure (34%) and reduced range of emotions (32%) associated
with ADM.
In this audit, GPs were encouraged to consider patient
preferences and information from the RANZCP guidelines
when selecting ADM for their patients. Results showed
agomelatine was most commonly prescribed (42%), followed
by escitalopram (11%) and sertraline (10%).
In the post-audit evaluation, almost all GPs found TAILOR had either ‘entirely met’ (85%) or ‘partially met’ (14%)
the objective to tailor pharmacological management of depression. 100% of clinicians reported change in behaviour by
tailoring ADM to ensure efficacy and minimise side effect
concerns.
Conclusions: TAILOR identified the importance of involving
patients in the ADM decision making process. Most patients
rated risk of side effects and fear of becoming dependent
as the greatest concerns for starting treatment, while less
were concerned with no belief the medication would work.
GPs found the audit had met their objective and changed
behaviour post-audit.
Disclosure statement: I have received grants and honoraria
from Servier Australia Pty Ltd. Servier were the funders of
the TAILOR study
References
[1] Van Servellen, G., Heise, B., Ellis, R., 2011. Factors associated with antidepressant medication adherence and adherenceenhancement programmes: a systematic literature review.
Ment Health Fam Med 8 (4), 255–271.
[2] Malhi, G.S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P.B.,
Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G.,
Porter, R., Singh, A.B., 2015. Royal Australian and New Zealand
College of Psychiatrists clinical practice guidelines for mood
disorders. Aust N Z J Psychiatry 49 (12), 1087–1206.
doi: 10.1016/j.euroneuro.2018.11.518
S331
P.503 Association of polymorphic variants of genes of
kinase signaling pathways with atypical depression
N. Vyalova 1,∗, I. Losenkov 1, G. Simutkin 2, S. Ivanova 1
1
Mental Health Research Institute- Tomsk National Research Medical Center- Russian Academy of SciencesTomsk- Russia, laboratory of molecular genetics and biochemistry, Tomsk, Russia
2
Mental Health Research Institute- Tomsk National Research Medical Center- Russian Academy of SciencesTomsk- Russia, department of affective states, Tomsk, Russia
Background: Frequent clinical cases of atypical depression
caused an increase in scientific interest in this phenomenon
in recent years. Depression occurring with inverted vegetative signs is a poorly understood problem, causing many
questions in terms of diagnosis, etiology, pathogenesis,
treatment and prognosis. The study of kinase signaling pathways is a new and rapidly developing direction in the field
of neuronal signal transduction, which is associated with the
disturbance of neurobiological processes in mental disorders
[1]. The purpose of our study was to study the possible association of polymorphic variants of the genes of kinase signaling pathways PIP5K2A, SGK1, GSK3B, AKT1 with the presence of typical or atypical depressive symptoms.
Methods: Genotyping of DNA samples of 306 patients with
depressive disorders aged 20 to 60 years, undergoing treatment in the department of affective states of the Mental
Health Research Institute clinics. The severity of depressive symptoms, as well as the evaluation of the severity of
typical and atypical depressive symptoms, used the SIGHSAD scale, which includes 17 items of the Hamilton Depression Scale and 7 points evaluating atypical depressive
symptoms (social withdrawal, increased appetite, weight
gain, increased intake of food, carbohydrate food preferences, hypersomnia, fatigue). In the examined individuals,
blood from the ulnar vein was collected for genetic studies, followed by isolation of genomic DNA using the phenolchloroform micromethode. Genotyping of polymorphic variants of the genes PIP5K2A, SGK1, GSK3B, AKT1 was carried
out by real-time PCR on the Step One Plus TM Real-Time PCR
System (Applied Biosystems, USA) using TaqMan1 Validated
SNP Genotyping Assay kits (Applied Biosystems, USA). Studied polymorphic variants rs1417374, rs946961, rs1132816,
rs11013052, rs943190, rs10828317, rs10430590, rs746203,
rs8341 gene PIP5K2A, rs1057293, rs9373085, rs1743964,
rs1743966, rs1743939, rs1743940 gene SGK1, rs6438552 and
rs334558 gene GSK3B and rs1130214, rs3730358 AKT1 gene.
The statistical processing of the results was carried out using the SPSS program, version 20.0.
Results: A study of the relationship of the polymorphic variants of the PIP5K2A, SGK1, GSK3B, and AKT1 genes studied
to the presence of typical or atypical depressive symptoms
assessed by the SIGH-SAD scale showed the association of
the polymorphic variants rs8341 (p = 0.033) and rs746203
(p = 0.035) of the PIP5K2A gene with an average sum points
on the SIGH-SAD scale for typical depressive symptoms on
the 14th day of therapy against a statistically significant decrease in scores, which corresponded to an improvement in
Keep reading this paper — and 50 million others — with a free Academia account
Used by leading Academics
Richard Matasic
University of medicine Zagreb
Hassan Djavadzadegan
Tabriz University Of Medical Sciences
Stefano Masi
University College London
Roberto Gouvêa Silva Diniz
Universidade de Pernambuco - UPE (Brasil)
