P-05-01

Effects of the metabotropic glutamate type II receptor agonist LY544344 on panic anxiety induced by cholecystokinin tetrapeptide in healthy volunteers

M. Kellner, C. Muhtz, A. Yassouridis, K. Stark, J. Arlt, K. Wiedemann. UKE Hamburg Psychiatric und Psychotherapie, Hamburg, Germany

Objective: Preclinical studies have repeatedly shown an anxiolytic-like action of type II metabotropic glutamate receptor agonists, such as LY544344 and LY354740. We tested whether LY544344, a prodrug of LY354740, would 1) reduce cholecystokinin tetrapeptide (CCK-4)-induced panic anxiety and 2) reduce CCK-4 activated stress hormone secretion in normal man.

Methods: Twelve healthy male volunteers were treated with LY544344 (80 mg bid po) or placebo for one week each in a double blind, randomized crossover design, with a two-week washout between treatment periods. On day 8 of each treatment period, CCK-4 challenges (50 μg iv bolus) were performed at 11:00. Panic and anxiety were assessed by panic questionnaires and visual analogue scales for anxiety and tension. Adrenocorticotropic hormone (ACTH) and cortisol levels were measured from 10:30 until 13:00.

Results: Analysis of variance did not show an overall significant main effect for treatment. However, in the 10 subjects who had a lower CCK-4 elicited ACTH release following LY544344 vs. placebo treatment, significantly fewer CCK-4-induced panic symptoms and significantly lower anxiety ratings were detected.

Conclusion: Our preliminary results suggest that additional studies with a larger number of study subjects are needed to further clarify the potential of the metabotropic glutamate type II receptor agonist LY544344 as a new anxiolytic or anti-panic drug in humans.

P-05-02

Modulation of the autonomic nervous system during CCK-4 challenge

J. C. Arlt, M. Kellner, H. Jahn, T. Raedler, A. Yassouridis, K. Wiedemann. Univers.klinik Hamburg-Eppend. Kl. f. Psychiatr. u. Psychoth., Hamburg, Germany

Objective: By the method of HRV we examined the effects of CCK-4 regarding to the ANS with healthy male volunteers. CCK- 4 is a panic provoking agent with a rapid onset of typical symptoms. The presumably central effects on HR are short(I-2 min.), so that investigation of HRV likely reveals autonomic effects independent from psychopathology or endocrinology.

Methods: 19 healthy male volunteers (30.0 +/-1.5) obtained a CCK-4-bolus injection of 50 lag at 11:00, after an intravenous cannula was inserted into a forearm vein at 9:00. ECG was continously recorded by a digital Medilog AR-12 holter equipment (Oxford instruments). Blood pressure was monitored sphygmomanometrically in distinct intervals. A HRV analysis was performed after exclusion of ECG arrhythmias and artefacts and certain measurements of the standard and frequency domain were calculated from 1-min segments. Three time intervals were extracted from the entire data sampling period: Before injection (Pre), immediately after injection (Bolus) and thereafter(Post).

Results: The following effects after CCK-4 bolus were observed (all values as ML): We found a high correlation of RMSSD and pNN50 to the HF component (Fig. 2). These results indicate a loss of parasympathetic tone: RMSSD decreased by 38.2%, pNN50 even by 56.4%, HF by 42.3% (Fig. 2) and HF norm by 23.0% (Fig. 1). The rise of the so-called sympathovagal balance (LF/HF) by 50.3% indicated a shift from vagal to sympathetic activity (Fig. 3). Furthermore we observed an activation of sympathetic tone, represented in LF norm, which was enhanced by 9.7% after CCK-4 administration (Fig. 1). In addition a rapidly increasing HR by 40.2% was found, which was accompanied by a simultaneous decrease of TP by 27.3% (Fig. 3).

Conclusion: Our results of a a lowered vagal tone and a sympathetic activation by administration of 50 ~tg CCK-4 (Fig. 1) supports the notion, that also panic attacks could be associated with alterations of the ANS independent from psychopathology. Also a higher cardiovascular risk because of alterations of the ANS can be assumed. Further studies in panic patients are warranted.

P-05-03

Concentrations of the neuroactive steroid 3α, 5α Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) after panic induction with cholecystokinin-tetrapeptide (CCK-4)

D. Eser, F. di Michele, P. Zwanzger, A. Pasini, T. C. Baghai, C. Schiile, E. Romeo, R. Rupprecht. Ludwig-Maximilian-Universtät Abt. Psychiatrie, München, Germany

Objective: 3α-reduced neuroactive steroids such as 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5αtetrahydrodeoxycorticosterone (3α, 5α-THDOC) are potent positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In preclinical studies a pronounced anxiolytic activity has been shown for those 3α-reduced neuroactive steroids. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3α, 5α-THP concentrations in patients with panic disorder but not in healthy controls. While various studies show an increase in ACTH and cortisol secretion following challenge with CCK-4, no data are available on 3α, 5α-THDOC levels during experimentally induced panic in humans.

Methods: We quantified 3α, 5α-THDOC .concentrations in 10 healthy volunteers (9 men, 1 woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. Panic symptoms were assessed with the Acute Panic Inventory (API) at baseline and after CCK-4 injection.

Results: CCK-4 elicited a strong panic response accompanied by an increase in 3cq 5cc-THDOC, ACTH and cortisol concentrations.

Conclusion: The main finding of our study is that experimental panic induction with CCK-4 is not only accompanied by a stimulation of ACTH and cortisol release but also by a pronounced increase in 3α, 5α-THDOC plasma concentrations in healthy volunteers. This increase might be a consequence of hypothalamicpituary adrenal axis activation following CCK-4 induced panic and might contribute to the termination of the anxiety response following challenge with CCK-4.

P-05-04

The symptom structure of panic disorder, agoraphobia and social phobia

A. S. Kristensen, O. Mors. Psykiatrisk Hospital i Aarhus C. f Basic Psychiatric Researc, Risskov, Denmark

Objective: The possibility of subtypes of anxiety disorders is of importance not only to the understanding and treatment of anxiety disorders, but also to genetic and neurobiological research. The aim of this study is to investigate the symptom structure of the ICD-10 anxiety symptoms in Danish patients with panic disorder, agoraphobia or social phobia.

Methods: Approximately 120 patients, who fulfil the ICD-10 diagnostic criteria for panic disorder, agoraphobia and/or social phobia before the age of 21, i.e. with early onset, are included in the study. Anxiety symptoms are assessed both through a semistructured diagnostic interview (SCAN) determining whether the 14 bodily and cognitive ICD-10 anxiety symptoms are present, and through a self-completion questionnaire in which the ICD-10 symptoms subdivides into 28 items and presence is assessed on a 5-point Likert scale. Factor structure is examined through principal component analysis, eigenvalue > 1, and scree test.

Results: The two different methods do not yield identical factor structure. In some cases the questionnaire/subdivision method gives more coherent factors than the SCAN method. In other cases, the subdivision method illustrates that symptoms, which are usually considered to be one symptom in the ICD-10, do not load on the same factor.

Conclusion: A wider selection of anxiety symptoms, than the 13 or 14 symptoms most often included, might be fruitful in future studies of symptom structure.

P-05-05

Social phobia with sudden onset - Is it really panic disorder with social phobia?

A. S. Kristensen, O. Mors. Psykiatrisk Hospital i Aarhus C. f Basic Psychiatric Researc, Risskov, Denmark

Objective: The hypothesis of this study is that sudden-onset social phobia is a parallel to panic disorder with agoraphobia. It is possible that at least some instances of social phobia might develop because the patients experience panic attacks in social situations. The study will investigate whether there are differences between sudden-onset social phobia and ordinary social phobia with regards to physical symptoms, number of avoidance situations, age of onset or correlating temperamental traits. Also, it will be investigated whether sudden-onset social phobia resemble panic disorder, or comorbid panic disorder and social phobia more than it resembles ordinary social phobia with regards to physical symptoms, age of onset and correlating temperamental traits.

Methods: The sample will consist of at least 120 patients, who fulfil the ICD- 10 diagnostic criteria for panic disorder and/or social phobia. The patients are divided into four groups: Those with panic disorder, those with comorbid panic disorder and social phobia, those with sudden-onset social phobia, defined as acute onset and remembrance of onset situation, and those with social phobia without sudden onset. They are asked about the presence of a wide range of anxiety symptoms, about specific avoidance behaviours, and about age of onset. They also complete the Revised NEO Personality Inventory and the IPC Locus of Control questionnaire. Differences between the groups of patients with ordinary social phobia and sudden-onset social phobia will be investigated using Independent-Samples T Test. Differences between all four groups of patients will be investigated using One-Way ANOVA.

P-05-06

Particularities of the onset of panic disorder

D. Podea, "Vasile Goldis" Western University of Arad, Arad, Romania

Objective: the study aimed to establish corelations between the on set of panic disorder and seasonal rhythm, circadian rhythm, the circumstances and place of occurrence of the attacks, the sufferer's attitude towards the first panic attack and the period between the first and the second panic attacck.

Methods: the study was conducted on 80 patients hospitalized in the psychiatric clinic of arad between 1999-2004. the research was conducted comparatively by dividing the patients into two groups: group "a" consisting of 44 patients diagnosed with panic disorder with agoraphobia and soubgroup "b" consisting of 36 patients diagnosed with panic diosrder without agoraphobia, the first diagnosis of panic disorder with or without agoraphobia was established on dsm-iv and icd-10 operational criteria, resorting to the dsm-iv criteria of diagnosis, the on set of panic disorder was determined with accuracy, namwly 6 months prior to the first interview.

Results: the first panic attack appears more frequently in late spring and in summer (between march and august) and more seldom in autumn and winter (between september and february). 70 subjects (87,50%) experienced the first panic attack in the period may-august where as only 10 subjects (12,50%) in the period september- april (p 20,5). therefore, the incidence of the disorder is higher during the hot season than during the cold seasons, the most panic attacks occur early in the day (between 7 am and 11 am), only 10%happening at night (between bedtime and 6 am). the study of circadian rhythm of panic disorder has shown that anxious symptomatology is more intense in the morning (between 7 am and 11 am) and in the evening (between 7 pm and bedtime) than in other times, in panic disorder without agoraphobia, attacks frequently occur at home or at work (66,66% - 24 subjects), and more rarely in phobic situation, such as waiting for the bus or riding one (11,11% - 4 subjects), most of the attacks in panic disorder with agoraphobia occur in phobic situations (93,19%) and only rarely at home (6,81%) .the most frequent circumstances of occurance of the panic attacks were: public places (disco, mall, stadium, downtown), in crowds (market places), on bridges or in tunnels (51, 02 - 21 subjects) or while waiting for means of transport or travelling by them alone (26, 82% - 11 patients), or in a car (19, 51% -9 subjects).in relation to the subjects attitude towards their first panic attack, it was conclused that 75% (60 patients) instantly ran from the place where they experienced the first panic attack, whereas most of the others felt the urge to run, but couldn't do so since they were in the moving vehicle, only a few 6,25% (5 patients) were able to restrain themselves.an interesting aspect is the fact than 78, 75%of the subjects diagnosed with or without agoraphobia (63 patients) requested medical assistance, from various departaments: family psysicians, cardiologists, psychiatrists, emergency wards as well as from workers, as a result: 32 patients (40%) requested medical assistance in less than 24 hours; 16 patients (20%) requested assistance from emergency services. 12 patients (15%) from other specialists (bioenergy, acupuncture, yoga) or psychologists and 20 patients (25%) requested assistance from a familiar psysician, analiysing the period of the time between the first and the second panic attack, it was concluded that: 32 patients (40%) developed other panic attacks in less than a week. 12 patients (15%) developed another panic attack within 3 months; 10 patients (12,5%) developed new panic attacks 3 months or even a year later and at 26 patients (32,50%). a new panic followed after a year or event more (1-4 years).

Conclusion: all these observations clearly proove that the study of the onset of panic disorder can help establish it's relation ships not only with gender, age, education but also with the seasonal and circadian rhythms, as well as the circumstances and place of occurance of the first panic attack.

P-05-07

Evidence-based therapy of panic disorder in a Spanish sample

E. Gallego-Tomas, M. Checa-Casado, P. Casaus-Samatan, A. B. Castella-Culvi, A. Labad-Alquezar, J. A. Gutierrez-Zotes. Ctra del Institut Pere Mata, Reus, Spain

Objective: Efficacy assessment of the Cognitive Behavioural Therapy Program (CBTP) of the panic disorder developed in our Mental Health Centre (MHC) METHOD Fourteen subjects, 9 women and 5 men, Panic Disorder diagnosed by DSM IV-R, completed intensive group therapy (14 weekly sessions of one hour and a half). The therapy contents were: psychoeducation, self-relax techniques, cognitive therapy and exposition to the fear conditioned situations. Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI), administered in first and last sessions of the therapy, were the assessment instruments used in this study.

Results: A statistical significant difference between test and retest measurements was found, showing a decrease in both, anxiety and depression symptoms. The most improved areas were: failure feeling, environment satisfaction, physical self image, tiredness, appetite, health worries, sex interest, calm sensation, security, self confidence, nervousness, happiness, restness, decision making, stress and crisis and difficulties coping tendency.

Conclusions: The CBTP developed in our MHC appears as an effective therapy for the panic disorder in an ambulatory patients sample. Both, anxiety and depression symptoms are benefited by the treatment.

P-05-08

Study of the relationship between anxiety and depression among students of Islamic Azad University-Iran

A. A. Bayani. Islamic Azad university Psychology, Azadshahr. Iran

Objective: The main purpose of the present study was to examine the relationship between anxiety and depression among students of Islamic Azad university.

Methods: Participants: Participants were 549 undergraduate students of Islamic Azad university of Azadshar.The mean age of participants was 22.7 years(SD=4.58)and ages from 18 to 30 years old.The were 245 men and 324 women. Measures:All participants completed a questionnaire booklet containing two self-report measures.The State-Trait Anxiety Inventory (STAI)oF Spilberger and Beck Depression Inventory(BDI).

Results: The deta were analyzed by means of the SPSS Statistical package,using the frequency and correlation.The results of the present study demonstrate that correlation between anxiety and student's depression is meaningful and positive(r=0.596 α=0.01)

Conclusion: The present study revealed that anxiety is associated with self-reported depression.This research supported previous literature's findings that anxiety is related to depression.

P-05-09

A study of GPs' diagnostic skills concerning major depressive episode and generalized anxiety disorder

I. Ostby-Deglum, A. Mykletun, A. A. Dalai. Sykehuset Innlandet HF Division Psychiatry, Ottestad, Norway

Objective: 1) To compare GPs" true and believed diagnostic skills in relation to major depressive episode (MDE) and generalized anxiety disorder (GAD), and 2) To examine to what extent GPs have insight into their own diagnostic skills.

Methods: In a cross-sectional designed study 38 Norwegian GPs examined 15-28 patients each in their practice (total 724). The presence of MDE and GAD were rated by the GPs on the Clinical Global Impression-Severity Scale (CGI-S). The reference standards of GAD and MDE were assessed by their patients according to DSM-IV criteria based scales, and the Hospital Anxiety and Depression Scale (HADS). True diagnostic skills were operationalized as concurrence between CGI-S and the reference standards. Believed diagnostic skills were rated by the GPs on a four-point Likert-scale.

Results: GPs judgment of levels of MDE and GAD concurred 40% and 26% with the standards, respectively. Comparison between true and beIieved diagnostic skills showed that GPs overestimated their diagnostic skills. No associations between true and believed diagnostic skills concerning MDE (p=0.70) and GAD (p = 0.65) were found.

Conclusion: The moderate level of true diagnostic skills and the gap to believed diagnostic skills, indicate the need for GPs toget insight into their diagnostic skills concerning common mental disorders.

P-05-10

Escitalopram in the treatment of anxiety symptoms associated with depression

B. Bandelow. University of Göttingen Dept. of Psychiatry, Göttingen, Germany

Objective: Comorbidities are common in real life, and it is important to examine comorbid depression/anxiety, since both depressive and anxious symptoms need to improve with treatment to achieve stable remission. In the present paper, the effect of the selective serotonin reuptake inhibitor escitalopram in treating the symptoms of anxiety in patients with major depression (without comorbid anxiety) was investigated.

Methods: Data from five previously published escitalopram studies that included a placebo arm were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the 'inner tension' item (item 3) of the Montgomery-]ksberg Depression Rating Scale. In three of the studies, anxiety symptoms were also assessed, either continuously over time or at baseline and endpoint, by using the Hamilton Rating Scale for Anxiety (HAMA), the 'anxious mood' item of the HAMA (item 1), the Psychic Anxiety subscale of the HAMA (items 1-6 and 14), the 'psychic anxiety' item of the Hamilton Rating Scale for Depression (HAMD; item 10), and the Anxiety/Somatization subfactor of the HAMD (items 10-13, 15, and 17).

Results: In all comparisons, mean improvement for escitalopram was significantly greater than for placebo, in some comparisons, escitalopram also showed a significantly earlier onset of action or an earlier separation from placebo than citalopram.

Conclusion: Anxiety symptoms in depressed patients can effectively be treated with escitalopram and a more stable remission might therefore be achieved.

P-05-11

Pregabalin demonstrates onset of significant anxiolytic efficacy as early as week one

S. Montgomery, J. Brock, K. Tobias, G. Zornberg, G. Farfel. London, United Kingdom

Objective: Pregabalin is a novel anxiolytic that has demonstrated robust efficacy for the treatment of psychic and somatic symptoms of generalized anxiety disorder (GAD) in 5 of 6 randomized clinical trials. The goal of this analysis was to evaluate the speed of onset of pregabalin' s effect for relieving the symptoms of GAD.

Methods: Data were analyzed for doses ranging from 200 to 600 mg pregabalin from 6 placebo-controlled trials of pregabalin (including those with active comparators, lorazepam, alprazolam, or venlafaxine) in patients with GAD (pregabalin-treated patients: N=939; female=60%; mean age=39 years; baseline HAM-A=26). Endpoints analyzed included sustained improvement in HAM-A total score at the first assessment at Week 1 that was significantly improved at every visit thereafter and proportion of patients with early improvement (≥30% reduction in HAM-A by Week 1).

Results: Pregabalin demonstrated significant improvement in every fixed-dose treatment group from 200 to 600 rag/day. Significant and sustained Week 1 improvement was achieved with pregabalin, from the 200-mg dose (52%) to the 600-mg dose (54%) versus placebo (30%; p<0.001 for both comparisons). Significant early improvement was observed by Week 1 in both the HAM-A psychic and somatic factors. Alprazolam and venlafaxine were not statistically significantly different from placebo at Week 1; lorazepam was associated with significant improvement at Week 1 but had the highest rate of discontinuations due to adverse events.

Conclusion: Pregabalin demonstrates rapid anxiolytic efficacy as early as Week 1. The magnitude of early improvement was greater for pregabalin than for either alprazolam or venlafaxine.

P-05-12

Efficacy of Ppregabalin in GAD by demographics and baseline severity

M. Pollack, G. Zornberg, J. Brock, K. Tobias, G. Farfel. Massachusetts General Hospital Psychiatry, Boston, USA

Objective: Pregabalin has been shown to efficaciously treat the psychic and somatic symptoms of generalized anxiety disorder (GAD). This analysis evaluated the efficacy of pregabalin across several clinically relevant subtypes of GAD patients, looking at age, gender, and baseline symptom severity.

Methods: Data were collected from 5 placebo-controlled studies of pregabalin as treatment for GAD. Pregabalin dosage groups (200 to 600 rag/day) were combined to yield the analysis sample, N=1282; female=60%; mean age=39.4 yrs; base HAMA= 25.4. Subgroups analyzed included those defined by the following variables: gender, age, severity (baseline HAM-A≥26), subsyndromic depression (baseline HAM-D≥15), severe somatic symptoms (baseline HAM-A somatic factor ≥12), and severe insomnia (baseline HAM-D items 4-6 ≥4). A Week 4 LOCFendpoint analysis was performed with responders defined as those having ≥50% reduction in HAM-A total score.

Results: Responder rates were significantly higher for pregabalin than placebo among males (56% versus 39%; p<0.001), females (51% versus 32%; p<0.001), and the elderly (55% versus 27%; p<0.02) and among patients with severe anxiety (56% versus 36%; p<0.001), subsyndromic depression (49% versus 31%; p<0.001), severe somatic symptoms (57% versus 35%; p<0.0001), or severe insomnia (56% versus 35%; p<0.001). Significantly greater improvement was observed in symptom factors used to define high-severity subgroups, including HAM-A somatic factor (Week 4 LOCF-endpoint change score, -7.3±4.8 versus -5.8±4.6; p<0.0001).

Conclusion: Pregabalin demonstrates broad-spectrum efficacy across clinically relevant subgroups in GAD, including the elderly, males and females, and patients with severe anxiety, severe insomnia, or severe somatic symptomatology.

P-05-13

Pregabalin's sustained effects in treating somatic symptoms in patients with gad

K. Rickels, F. Mandel, G. Farfel, G. Zomberg. Univ Pennsylvania Med Center Psychiatry, Philadelphia, USA

Objective: To better understand the persistence of improvement with pregabalin, the novel anxiolytic, which has demonstrated significant efficacy in improving physical-somatic, as well as the emotional, symptoms of anxiety in 5 of 6 placebo controlled trials of acute treatment of generalized anxiety disorder (GAD).

Methods: Data from all 6 placebo-controlled trials of pregabalin in GAD (4-6 weeks in duration) were combined to analyze 3 clinically relevant treatment groups (low-dose, 150; middose, 200-450; or high-dose, 600 mg/day; total n=1149) compared with placebo (n—484). Responders to treatment were defined as those patients with ≥30% improvement on the HAM-A somatic factor score persisting at all visits or all except one. Median duration of the most common adverse events (AEs) was examined. Results: Significantly more patients treated with pregabalin (low-dose, 54.2%, p=0.03; mid-dose, 60.5%, p<0.0001; high-dose, 60.5%, p<0.0001) than with placebo (41.9%) responded to pregabalin. Discontinuation rates due to adverse events for the low- (6.2%) and mid-dose (8.3%) pregabalin treatment groups were lower than in the placebo group (9.3%) and high-dose pregabalin group (18.0%). The most common AEs were somatic symptoms—somnolence and dizziness. Median duration of somnolence and dizziness was 9 and 16 days on pregabalin compared with 8 and 10 days on placebo.

Conclusion: Pregabalin demonstrated robust efficacy—which persisted throughout the course of treatment—for relieving the physical-somatic symptoms of GAD. The optimal dosing for pregabalin as treatment of GAD appears to be in the 200- to 450- mg/day range. The most common AEs associated with pregabalin treatment were transient and intermittent.

P-05-14

Drug abusers suffering from social phobia show more avoidance tendencies than patients with social phobia alone

A. Buecking, M. Stankovic, G. Zimmermann, S. Krenz, Y. Khazaal, F. Borgeat, D. F. Zullino. University of Lausanne Department of Psychiatry, Prilly-Lausanne, Switzerland

Objective: There is a high degree of comorbidity between social anxiety disorder (SAD) and substance use disorders (SUD). SAD typically precedes the development of SUD. Thus, it has been postulated that the typical avoidance found in SAD may be a contributing factor for developing SUD. The aim of the present study was to test the hypothesis that in SAD patients presenting comorbid SUD the avoidance symptoms would be relatively more prominent compared to patients suffering from SAD only.

Methods: Thirty patients presenting SAD and comorbid SUD were recruited in the in- and outpatient facilities of the Substance Abuse Unit of the University Department of Psychiatry, and 30 patients with SAD only were identified by the Clinical Research Unit through an advertising program, addressing patients from the general population. All patients were asked to answer the Liebowitz Social Anxiety Scale.

Results: Patients suffering from SAD and SUD showed a significantly higher Avoidance/Anxiety ratio, avoidance contributing at mean to 49.7% (±4.9%) of the total score in patients with SAD&SUD, whereas its mean contribution was 46.3% (±3.2%) in patients with SAD only (Z=-3.11 ; p=0.002).

Conclusion: The results confirm that avoidance plays an especially important role in the cognitive patterns of patients suffering from SAD and SUD, suggesting that they may play a critical role for developing drug abuse. This may be of particular therapeutic interest, as it suggests that treatment should particularly focus on the maladaptive coping of avoidance in these patients.

P-05-15

Clinical subgroups in social anxiety disorder (SAD)

M. Lader, D. Stein, D. Stein, E. W. Andersen, R. Nil. Institute of Psychiatry Psychiatry, London, United Kingdom

Objective: In this previous study, a factor analysis of the primary efficacy parameter, the 24-item Liebowitz Social Anxiety Scale (LSAS), revealed 6 LSAS factors (social interaction, eating and drinking in public, speaking in public, functioning in public, writing/working, partying), which were all responsive to treatment. The results from a placebo-controlled, fixed-dose escitalopram study using paroxetine as active reference were analysed on the basis of these LSAS factors.

Methods: Each of the 6 factors and 24 single items were analysed separately, using observed cases, for the effect of escitalopram at week 24, using ANCOVA with treatment and centre as factors and baseline subscale as covariate. Data were from a randomised, double-blind, 24-week trial in SAD, which included escitalopram 5mg/day (n= 167), 10mg/day (n= 167), and 20mg/day (n=170), paroxetine 20mg/day (n=169), and placebo (n=166).

Results: Using the 6-factor model, escitalopram 5rag, 10mg, and 20mg were generally more effective than placebo for each of the factors. Escitalopram 20mg was rically better for factor 4 (functioning in public), and statistically significantly superior to paroxetine 20mg for the other 5 factors (p<0.05). Escitalopram 20mg was more effective than paroxetine 20mg on all of the single items, apart from item 18 (expressing disagreement or disapproval to people you don't know very well).

Conclusion: The present study demonstrated a better efficacy of escitalopram 20mg than the recommended 20mg dose of paroxetine across most areas of generalised SAD.

P-05-16

Impaired word recognition in obsessive-compulsive disorder: An event-related potential study

Y. Zhang, S. Feutl, T. Grdeeke-Koch, C. Riehter-Witte, U. Hauser, P. Schmorl, J. Schramm, H. Emrich, D. E. Dietrich. Medizinische Hochschule Psychiatrie und Psychotherapie, Hannover, Germany

Objective: Memory disturbances are found in obsessivecompulsive disorder (OCD). Brain imaging studies indicate a dysfunction of the orbital prefrontal cortex, caudate nuclei and anterior cingulate in OCD. Event-related potential (ERP) is a sensitive technique to investigate the time course of working memory processes. However, there are no such data on word recognition memory in OCD. Therefore, the memory recollection processing for words was explored in OCD compared to healthy controls.

Methods: A visual continuous word recognition paradigm was performed in a group of OCD (n=16) and a control group (n=16) with matched age, gender and education. 300 German words were presented serially in white color on a computer display. The subjects" task was to discriminate between f'trst (new) and second (old) word presentation by pressing one of two buttons with left or right index finger. Brain responses to repeated items are characterized by more positive waveforms of ERPs in the timewindow 200-800 ms after stimulus. This recognition (old/new) effect is shown by the ERP-difference for old minus new words.

Results: The old/new effect (420-660 ms post-stimulus) was reduced at left fronto-temporal electrode sites in OCD comparing the control group indicating disturbed recollection processes. Additionally, the old/new effect (280-340 ms) in OCD was negatively correlated with the Y-BOCS scores (I-10) at T5 (Pearson r = -0.50, p < 0.05), even more significantly with the YBOCS obsessional scores (1-5) (Pearson r = -0.65, p < 0.01).

Conclusion: Impaired word recollection processing in OCD appears to be reflected by changes of the ERP old/new effect. Furthermore, the severity of obsessions is suggested to influence familiarity-based recognition.

P-05-17

Comparison of 18F-FDG PET and 1HMRS data in patients with intractable forms of anxiety-obsessive disorders (AOD)

A. Stanzhevsky, A. Korzenev, L. Tyutin, A. Pozdniakov, N., T. Skoromets. CRIRR Radiology and Nuclear Medicine, Saint- Petersburg, Russia

Objective: Studies of recent years showed a glucose metabolism decrease in caudate heads (CH) as pathognomic AOD sing. Besides a volume change was determined in CH in these patients according to MRI data. In this connection we had a task to compare PET and MRS techniques of the examinations aiming at further studying pathogenetic mechanisms of malignant AOD.

Methods: 18F-FDG PET and 1HMRS were performed in 16 patients with AOD and received data were compared with normal control group. With 1H MRS we studied changes in NAA, Cho and Cr concentrations in CH. Correlation of 1H MRS and 18F-FDG PET data was determinated.. Then PET and 1HMRS results were compared with the clinical state severity (Y-BOCS and Spilberger scale (SS).

Results: 18F-FDG PET revealed hypometabolism in CH in 11 patients as compared to the normal control group. 1HMRS showed decrease of NAA and increase of the Cho and Cr peaks in 9 cases. Metabolic and clinical data significantly intercorrelated (r Spearmen =0,58 for PET andlH MRS, p<0.05, r =0,46 and 0,39, p<0.05, for PET, MRS and clinical state respectively).

Conclusion: These data allow to suggest that hypometabolism in CH in AOD cases is dealt with substitution of neurons by glia cells that is confirmed by 1HMRS data. It can also be suggested that to develop techniques of surgical treatment for incurable AOD forms in the nearest future we can use chronic stimulation of CH via stereotactic-implanting electrodes and/or via stem cells transplantation in them.

P-05-18

Pathogenesis of malignant forms of anxiety-obsessive disorders (AOD) and assessment of objective findings for surgical treatment to be planned

A. Stanzhevsky, A. Korzenev, L. Tyutin, A. Pozdniakov, N. Kostenikov, N. Neznanov, T. Skoromets, V. Shamrey, E. Abritalin. CRIRR Radiology and Nuclear Medicine, Saint-Petersburg, Russia

Objective: Up to the present criteria for directing therapeutically incurable AOD forms for surgical treatment to be performed were only clinical state scales and exhaust of any other available therapy methods. Functional neuroimaging methods provide the potential for a more strict approach towards formation of findings for a surgical procedure to be recommended.

Methods: 18F-FDG PET was performed in 16 patients with resistant AOD forms before and after psychopharmacotherapy, and in a year after the psychosurgical treatment.

Results: It is seen that hypermetabolism in the anterior cingulate (AC), orbitofrontal cortex or hypometabolism in caudate heads (CH) and thalami that is not suppressed by subtoxic doses of drugs can serve as a marker in order to reveal proper findings for psychosurgical interventions. Relative positive correlation was determinated between metabolic changes intensity and clinical manifestations severity in all patients before and after treatment. Besides, 18F-FDG PET was performed in 6 patients who were their nearest relatives (for 3 parents and for their 3 children) with a treatment cancel. In all cases hypermetabolism was observed in AC and hypometabolism in CH. These changes in children had a more marked nature as compared to their parents. In families of all these patients a matriarchate life stile was noted.

Conclusion: Thus, we can suggest one of the mechanisms of AOD formation: with the background of hereditary-transferred "defects" in limbicostriatal system there is development and/or fixation of biochemical disorders under the influence of external behavior factors - directive hyper care rendered by mother and lack of any care expressed by father.

P-05-19

Neurasthenia managing by Enerion

N. Butorina, E. Bondarchuk. Ural State Medical Academy for Advanced Education, Chelyabinsk, Russia

Objective: The purpose was to study efficiency of an Enerion at the patients with neurasthenia.

Methods: There were selected 58 patients in the age of 40-55 years. The subjective scale of asthenia MP 1-20 was applied for estimation of asthenia level. The visual analog of asthenia scale was used to define the degree of asthenia. The surveyed patients were divided into two groups of 29 individuals each. At the first group Enerion was nominated as monotherapy The second group received Nootropil.

Results: The comparative analysis has shown a high efficiency of Enerion that has revealed a distinct anti-asthenia action already by the end of the first week of treatment. Upon termination of therapy asthenia had reparative dynamics in the first group at 23 patients and indulgence of asthenia symptoms at 6 persons. In the second group, the attributes of asthenia have disappeared only at 10 patients, and its indulgence was observed at 19 patients. Besides, the collateral symptoms of psychotropic action were marked. Therapeutic effect in the first group came in 1,5 times faster, than in second group. Enerion rendered positive therapeutic action not only on asthenia syndrome, but also on inherent to neurasthenia vegetative dysfunction, disturbing and subdepressive disorders, cognitive impairment.

Conclusions: Reparative processes at the patients with asthenia symptoms at reception of a medicine are much higher, than at those not accepting it. The study of Enerion enables to considerate as one of a basic anti-asthenia drug.