SYMPOSIA

Abstracts of the Invited Speakers
profile of these drugs administered alone or in combination in rats. We have used the technique of brain microdialysis in rat frontal cortex,
to monitor extracellular levels of noradrenaline, dopamine and serotonin in response to peripheral administration of BZP and MDMA. We
were also able to monitor the animals for evidence of rodent serotonin syndrome. BZP (10mg/kg, i.p.) was able to elevate extracellular
levels of dopamine, noradrenaline and to a lesser extent, extracellular serotonin in rat frontal cortex. MDMA (3mg/kg, i.p.) potently
elevated extracellular serotonin and noradrenaline and to a lesser extent extracellular dopamine in frontal cortex. These neurochemical
effects lasted for at least 2 to 3 hours relative to saline treated control animals. Combined BZP and MDMA administration led to markedly
elevated extracellular levels of all three monoamines indicating the effects of the drugs were additive. BZP (10mg/kg, i.p.) caused marked
behavioral activation, for example, increased locomotor activity and rearing behavior, whereas MDMA (3mg/kg, i.p.) resulted in flat body
posture and less rearing. Similar to MDMA (3mg/kg, i.p.), BZP increased grooming, forepaw treading, sniffing and head weaving relative
to saline injected animals. We also investigated a 5-HT2A receptor antagonist, ketanserin (3mg/kg i.p.), to see if it could attenuate BZPinduced
behaviors. Ketanserin alone had little effect on rat behavior but when co-administered with BZP, was able to decrease locomotion
and rearing behavior. Interestingly, ketanserin had little effect on the increased sniffing and head weaving induced by BZP. At the doses
of drugs used in this study hyperthermia was not apparent in any of the animals but we were able to measure blood and brain levels
of BZP and MDMA hence we know bioavailability was not a problem. Overall, these results suggest that BZP and MDMA share certain
psychopharmacological and neurochemical properties in the rat. Furthermore, combined administration of BZP with MDMA leads to a
marked elevation of extracellular levels of all three monoamines in the frontal cortex rather than just serotonin which, if translated into
the clinical setting, may explain the agitation and sympathomimetic toxic syndrome reported in some patients. All animal studies were
conducted in accordance with the Canadian Council on Animal Care Guidelines and Policies with approval from the Animal Care and Use
Committee in Health Sciences for the University of Alberta. This work is supported with a grant from Canadian Institute of Health Sciences.
Key words: Ecstasy, (±) -3-4-methylenedioxymethamphetamine, 1-benzylpiperazine, serotonin syndrome, rat behaviour, brain microdialysis
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S35-6
[KL-03]
Unipolar versus bipolar depression in children: What do we know about the etiology,
diagnosis, and treatment?
Rasim Somer Diler
Department of Psychiatry, University of Pittsburgh, PA, US
E-mail: dilerrs@yahoo.com
Bipolar disorder (BP) is a familial and recurrent illness that significantly affects the child’s normal development. BP is often manifested by periods of
depression during which the child has significant psychosocial problems and increased risk for suicide. However, most clinical studies have focused
on the manic phase of the illness. The depressed phase of the illness in youth is less recognized and less often treated than mania. Moreover,
depressed youth with BP are more likely to have more severe depression, greater suicidality, and higher rates of comorbidities and functional
impairment relative to depressed youth with major depressive disorder (MDD or “unipolar depression”). However, it is difficult to clinically
differentiate the symptoms of BP depression from those of MDD. This issue is very important because youth with BP depression may be treated
with antidepressants that can precipitate an episode of mania or mixed BP symptoms. Also, it may take up to 10 years from the initial symptoms
of depression until BP is diagnosed and appropriate treatment is prescribed. Thus, early identification of BP youth, especially during depression, is
critical not only to improve the long-term prognosis of BP, but also to prevent inappropriate treatments for BP youth. As demonstrated recently in
BP adults, improving the accuracy of early diagnosis of BP in youth may be achieved by identifying objective neural biomarkers at an early age that
are specific to BP and not common to MDD. Treatment guidelines for BD in children and adolescents were recently developed, but the panel left out
depression and agreed that there was insufficient evidence to develop a treatment algorithm for it. Several studies suggest that there are effective
and well-tolerated treatment options (e.g., lithium, mood stabilizers, second-generation antipsychotics [SGA]) for manic or mixed episodes of BD
in youth; however, there are no maintenance studies in depressed children and adolescents with BP and available data for depressive episodes
in BP is limited to one small randomized and two open-label acute treatment studies in adolescents. Management of depression is very different
in BP depression than in MDD; antidepressants are widely used in MDD, but may exacerbate or induce mania and suicide in depressed BP youth.
Antidepressant monotherapy is therefore contraindicated for the treatment of BP depression, and studies in depressed BP adults show that
combining antidepressants with mood stabilizers may also not be effective. In conclusion, early differential diagnosis and treatment of depression
in youth is a key factor to enable youth to follow a normal developmental path and prevent an unrecoverable loss in their development.
Key words: Child, bipolar, depression, neuroimaging
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S36
S36 Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org