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I0-15-8 1Serotonergic Control of Melatonin Secretion: TheRole of 5-HT1A Receptors

PJ. Nathan. T.R. Norman , G.D. Burrows. Department ofPsychiatry,Austin and Repatriation Medical Centre, Melbourne

Melatonin (MT) is a hormone secreted from the pineal gland fromserotonin (5-HT). The nocturn al rise in MT occurs by activation oftl l-adrenergic receptors in the pineal gland. uj -adrenoceptors have alsobeen shown to modulate MT secretion, by potentiating the effect oftl,-adrenoceptors. Although MT is synthesised from 5-HT, the role ofserotonergic receptor subtypes in the control of melatonin production isnot clear. We investigated the effect of some full (S-20499 & t1esinoxan),partial (buspirone and ipsapirone ) and indirectly acting serotonin re­ceptor agonists (d-fenfluramine & paroxeinte), on day- and night-timeMT. d-Fenfluramine and paroxetine (20 mglkg) were the only drugsthat increased day-time MT (p < 0.01). At night, no significant effectwas seen with buspirone . ipsapirone and paroxetine (p > 0.05), whiled-fenfluramine and flesinoxan significantly increased melatonin at 20mg/kg (p < 0.01). S(+)-20499 on the other hand significantly increasedMT at both 10 mg (p < 0.01) and 20 mglkg (p < 0.001). The fact thatonly the indirectly acting agonists increased day-time melatonin suggeststhat acutely increasing 5-HT availability increases MT. At night, all 5-HTagonists tended to produce a dose related increase in MT. d-Fenfluraminesignificantly increased MT at 20 mg/kg, further supporting the hypothesisthat increasing the availability of 5-HT, stimulates both day- and night­time MT secretion. However both S(+)-20499 and flesinoxan significantlyincreased nocturnal MT. suggesting a role for 5· HTIA receptors in theregulation of MT secretion. The fact that the latter drugs had no effect dur­ing the day, but increased MT at night would suggest that a functionallycoupled f31-adrenergic receptor may be required (i.e similar to the situa­tion at night) for the effect of5- HTIA receptor stimulation to be mediated.The mechanism by which 5- HT IA receptors increase MT may be sim­ilar to that of ctl-adrenoceptors (i.e potentiation of the PI response).Confirmation of this hypothesis awaits further detailed experimen­tation.

I5-191Post-Traumatic Stress Disorder

1 8-19-1 I The Assessment of PTSD in Veterans

B. Raphael. Director, Centre f or Mental Health, North Sydney

This paper will present an overview of the assessment processes regardingveterans' and PTSD. the operation of the Repatriation Medical Authorityto determin ing satisfactory acceptable basis for PTSD decisions and pre­senting computerised processing whereby these decision tress are created,to provide optimal processes for veterans.

I8-19-21 Biological Paradigms of the Atlentional Processingin Post Traumatic Stress Disorder

A.c. Mcf-arlane, R. Clark . D. Weber, C. Galletly. Department ofPsychiatry, University ofAdelaide

The role of disordered memory is becoming an increasing focus ofresearch into post traumatic stress disorder. In particular, much interest isfocused on the laying down and retrieval of traumatic memories.

An alternate construct of post traumatic stress disorder. is that theseindividuals have difficulties with self monitoring and dealing with avariety of neutral environmental stimuli. These abnormalities of workingmemory have been investigated using an event related potential paradigm.Patients with post traumat ic stress disorder have been compared withpatients with chronic schizophrenia to investigate the specificity of thecognitive abnormalities in post traumatic stress disorder. This particularstudy has utilised a newly developed task, the tier task. to maximise theupgrading of recent memory.

These results confirm the findings from an earl ier study using the oddball task about the difficulty that post traumatic stress disorder sufferershave updating their working memory and defining salients. The relevance

S-19 Post-Traumatic Stress Disorder

to these to understanding the phenomonology of post traumatic stressdisorder will be discussed.

I8-19-31 Neuroendocrine Alterations in PTSD

R. Yehuda. Mount Sinai School of Medicine, New York, NY]OO29

Individuals with post traumatic stress disorder (PTSD) show hypothalam ic­pituitary-adrenal (HPA) axis alterations that are significantly differentfrom those observed in normal controls, other psychiatric patients , andtraumatised individuals without PTSD. PTSD patients show lower meanbasal 24-hr urinary cortisol excretion. and larger number of lympho­cyte glucocorticoid (GC) receptors than subjects in the above-ment ionedgroups. They also show an enhanced suppression of cortisol (rather thanthe classic pattern of "non-suppression" observed in depression ) follow­ing dexamethasone. More recently. using chronobiological analyses. wehave demonstrated that PTSD patients show a stronger circadian rhythmand an enhanced "signal-to-noise" ratio of cortisol compared to patientswith depression and normal controls, and an enhanced ACTH responseto metyrapone administration . In this presentation , the above studies willbe summarised and a model of HPA axis functioning in PTSD will bepresented. It will be proposed that the findings in PTSD result from anenhanced negative feedback inhibition of the HPA axis.

I8-19-4 1Naloxone Reveals Decreased Threshold forHypothalamic CRH Release in PTSD

R. Jackson, G. Hockings. J. Grice. W. Ward, M. Walters. G. Jensen.Neuroendocrine Research Unit, Greenslopes Private Hospital, Br isbane.Australia

Neuroendocrine markers for PTSD would be potentially useful in aidingdiagnosis and. possibly. in following the efficacy of treatment and in un­derstanding the underlying pathophysiology of the condition. The opioidantagonist, naloxone (nal), causes pituitary ACfH secretion by stimu­lating hypothalamic CRH release. Vasopressin (AVP) directly stimulatescorticotropes to release ACTH. Our studies were comparisons of theeffect on ACTH and cortisol secretion of: 1. Four step-wise incrementaldoses of nal (0. 6, 25 and 125 uglkg body weight IV) given to 13 maleVietnam War veterans with severe. combat-related PTSD (aged 40-48years) and to 7 healthy male volunteers (aged 20-46 years). and, 2. fourstep-wise incremental doses of AVP (0. l, 0.3. I and 3 units/70 kg bodyweight) to 7 male Vietnam War veterans with severe, combat-relatedPTSD (aged 43-45 years) and 5 healthy male volunteers (aged 20-46years). There was no history of drug or alcohol abuse in any patientwithin the previous two months. no major active medical illness nororganic brain syndromes. All tests were done in mid-afternoon . Six ofthe 13 patients each had a greater ACTH response to the lowest 2 dosesof naloxone (6 and 25 uglkg) than any of the other PTSD patients orany of the control subjects. This was statistically significant on subgroupanalysis. These differences in response could not be accounted for byassociated psychiatric conditions, psychotropic drugs nor an effect of age.In contrast to the naloxone studies there were no significant differences inresponse of the pituitary-adrenal axis between PTSD patients and normalsafter AVP administration. We conclude that there is a hypersensitivity tonaloxone-induced CRR release in some PTSD patients. whereas directpituitary stimulation with AVP is normal. This may be due to decreasedendogenous inhibitory opioid tone on the activity of hypothalamic CRH­secreting neurons, which can, therefore, be more easily reversed in thesePTSD patients.

Supported by the Australian Department of Veterans' Affairs. DrHockings was Edwin S. Tooth Research Scholar. The University ofQueensland.

I8-19-51 The Modified Dexamethasone Suppression Test(mDSn in Chronic PTSD

M. Hopwood, J. Marcina, T. Norman. P. Morris, I. Schweitzer.Department of Psychiatry, University ofMelbourne

Previous studies of chronic PTSD have identified abnormalities in theHPA axis, suggesting heightened negative feedback sensitivity, potentially