Meeting Reports

 

Marseille 2001 : Overshadowed But Not Eclipsed

EBPS – IGBP workshop on Schizophrenia Amsterdam 2000

New Advances in the Understanding and Treatment of Addiction Brighton 2002
Marseille 2001 : Overshadowed But Not Eclipsed

posted 17.10.2001

by David Sanger


It seems to have become a tradition that, as delegates leave an EBPS biennial meeting they can be heard saying, 'that was the best one yet.' Marseille was no exception. Once again, our conference attested to the vigour and vibrancy of behavioural pharmacology and demonstrated that our discipline has much to offer in the search for the fundamental principles of neuroscience and pharmacology and the discovery and development of new drugs for disorders of the brain. The science we shared at Marseille was naturally the major attraction of the meeting and will be dealt with in a detailed report by Marianne Amalric at a later date. However, it may be useful to reflect on some other aspects of the conference which guarantee that it will be memorable.

Of course, whenever delegates think back to this meeting they will find the scientific and social events inextricably linked in their minds with the horrifying terrorist attacks which took place in Manhattan and Washington on September the 11th. Our conference was overshadowed by this disaster but , one can hope, not completely ruined for the participants. As the frightening events unfolded before our eyes several symposia were inevitably lost but the EBPS and EBBS presidents dealt with the situation in a thoughtful and dignified way which certainly prevented the conference from degenerating into chaos. Delegates were called together on the Tuesday afternoon and decided to meet again the next morning to decide whether the last day of the conference should go ahead as planned. Uppermost in everyone's mind were the many participants from North America, some of whom had friends or relatives in the vicinity of the World Trade Center. When Wednesday morning arrived it was clear that transatlantic flights had been suspended and that cancellation of the last day of the conference was neither necessary nor desirable. The clear decision of the delegates was to continue with the scheduled scientific events.

And so, despite the tragic international context, the EBPS once again triumphed in providing its members and other scientists with the very best of behavioural pharmacology in the most comfortable and attractive conditions. This conference was a joint meeting with the European Brain and Behaviour Society and although the EBPS has organized joint meeting with other societies in the past, notably with the American Behavioral Pharmacology Society and the British Association of Psychopharmacology, each event of this type brings new uncertainties. On this occasion, each society contributed a certain number of symposia and workshops and the organizing committee needed to take great care that all appropriate areas of science were covered without the conference giving the impression of being two separate meeting that just happened to be taking place at the same time under the same roof. This objective was achieved admirably. It could only have been the most insular of delegates who did not find that well over 50% of the meeting contents were of interest. Thus, the programme provided a clear demonstration of the complementarities of the two societies and augurs well for more contacts between us in the future.

The local organizing committee have already been thanked and indeed congratulated on their work but it is appropriate to take the opportunity of expressing our gratitude to Marianne Amalric, André Nieoullon, Christelle Baunez, Catherine Thinus-Blanc, Bruno Poucet and Bernard Soumireu-Mourat again using the written word. Everything about the local arrangements was superb. The conference centre at the Palais de Pharo was not only functional, providing exactly the right space for symposia, posters and social and other events, but was also situated in a most attractive spot. As Marseille's weather was also beautiful, we were able to enjoy views of the Mediterranean, strolls around the harbour and bouillabaisse to the full.

Over 500 delegates from many countries attended the meeting, the largest number ever at an EBPS conference. Many of these were young scientists and the EBPS can once again feel proud that it was able to assist many of its members with bursaries. It is the enthusiasm and imagination of young behavioural pharmacologists that will reinforce the growing strength of our discipline and the future of the EBPS. It is therefore, of major importance that many young scientists have the opportunity to take part in our conferences to present their work and have direct contact with their more senior colleagues. Although the EBPS is a relatively small society with limited funds, it has tried to offer financial support to young members whenever possible. At Marseille, a large number of bursaries were awarded. Significant funds were provided directly by the EBPS and the local organizers also worked very hard to obtain other sources of bursaries and sponsorship in which they were very successful. All sponsors will be thanked in the full conference report.

Although this recapitulation of the 2001 annual meeting is a reflection on a past event, it is surely appropriate to finish by looking ahead to the future. In 2003, the EBPS will hold its biennial conference in Antwerp with Thomas Steckler wearing the organizer's cap. This is a particularly significant occasion because it will mark 17 years since Francis Colpaert organized the very first full EBPS conference, also in Antwerp. Thus, 1986 represents the foundation of our society and thanks to the efforts of many individuals in the intervening years, the Society continues to thrive and to grow in strength and influence. So, Thomas, you have got a lot to live up to but all EBPS members are confident that we can look forward to a conference in Antwerp about which we will be able to conclude, 'that was the best one yet.
EBPS – IGBP workshop on Schizophrenia Amsterdam 2000

posted 08.02.2001

by B. A. Ellenbroek

From June 21st until June 24th the EBPS organised a workshop on schizophrenia in Amsterdam the Netherlands. This workshop was co-organised with the Dutch society for biological psychiatry (IGBP). Approximately 140 participants from 17 different countries discussed various aspects of this severe mental disorder in 4 days. Each session was devoted to one special subject and was introduced by a clinical and by a preclinical lecture, followed by three shorter talks on more specific new data.

The first session dealt with the neuropsychology of schizophrenia. The clinical introduction by Rob van den Bosch (NL) focussed on the main question of whether the cognitive deficit of schizophrenia is a generalised one or more restricted to specific domains. He provided evidence to support the idea that there is both a global deterioration in cognition in schizophrenic patients, but on top of that, specific domains, such as attention and verbal memory, are even more severely affected. Trevor Robbins (UK) discussed the relationship between the cognitive deficit, psychotic symptoms and stress and arousal in his preclinical introduction. He focussed predominantly on aspects of executive functioning, and the role different parts of the prefrontal cortex play in this cognitive domain. Angela Roberts (UK) followed up on this theme, by discussing the behavioural differences between lesions of the prefrontal cortex and 6-OHDA lesions of the dorsal striatum. She showed that the effects of a lesion of the prefrontal cortex were much more severe than those limited to the dopaminergic system. Margot Albus (Ger) discussed her recent work on the follow-up of first episode schizophrenic patients. Surprisingly, she found very little deterioration in the first two years. The final talk of the session was by Veena Kumari, who showed that the prepulse inhibition deficit in schizophrenic patients is reversible, when patients are treated with clozapine. Moreover she showed that early onset schizophrenia was accompanied by a large deficit in prepulse inhibition, which was abnormal even when the patients were treated with antipsychotics.

The second session was devoted to the treatment of schizophrenia, and aimed to discuss the similarities and differences between the classical and the atypical antipsychotics. Unfortunately, due to the illness of Hans den Boer, the clinical introduction could not be given. In his preclinical introduction, Gaetano di Chiara (Italy) focussed especially on the ability of classical and atypical antipsychotics to activate dopaminergic neurotransmission in the shell and core region on the nucleus accumbens and in the prefrontal cortex. He provided evidence that atypical antipsychotics, such as clozapine, olanzapine and risperidone induce a strong increase in the prefrontal cortex, but did not affect the core region of the nucleus accumbens. However, the increase in the prefrontal cortex was by no means specific for antipsychotics since both mianserine and reboxetine also strongly activate prefrontal cortex dopamine.  Wia Timmermans (NL) further investigated the effects of classical and atypical antipsychotics, thereby focussing predominantly on the output system of the basal ganglia. She showed that atypical but not classical antipsychotics reduced the firing rate of substantia nigra pars reticulata cells. This effect seemed to be related to the additional serotonin blocking effects of drugs such as clozapine and olanzapine. Anna Lena Nordstrom (Sweden) reported on PET studies investigating the in vivo occupancy of dopamine receptors in schizophrenic patients treated with various antipsychotics. Her data clearly showed that there were large individual differences between different antipsychotics. For instance for haloperidol striatal D2 binding levels of approximately 65% were necessary to obtain a clinical improvement in psychotic symptomatology, whereas occupancy of 72% or above lead to increases in prolactin secretion. Levels of 78% and above additionally induced extrapyramidal side effects. On the other hand, drugs such as clozapine and quetiapine reduced psychotic symptoms with occupancy rates of around 30 to 40%. One possible explanation for these discrepant findings may be the additional binding to extra-striatal dopamine receptors. As she showed, it is still very difficult to visualise these sites with PET studies. In the final presentation of this session Ronan Depoortere (F) discussed the preclinical data on a new antipsychotic of the benzamide class. Amisulpride appears to be a highly selective dopamine D2/3­ receptor antagonists, with limbic selectivity. It does not induce catalepsy and has little effect on dopamine agonist induced stereotypy.

Session 3 was devoted entirely to the information processing deficits that can be observed in schizophrenic patients. David Braff (USA) opened the session by giving an overview of the clinical studies on prepulse inhibition. In agreement with the data of Veena Kumari earlier on, he showed that the prepulse inhibition deficits in schizophrenic patients were reversible, and could be virtually normalised when patients were adequately treated. He also emphasised that this deficit was by no means specific for schizophrenic patients, but can also be observed in relatives of schizophrenic patients, as well as in patients suffering from  obsessive compulsive disorder, temporal lobe epilepsy, Huntington’s chorea and in psychotic prone subjects. Another important issue discussed was the functional consequences of prepulse inhibition deficits. Braff showed that prepulse inhibition was worse in those patients that show more perseverative errors in the Wisconsin Card Sorting Test and in those patients with severe thought disorder, suggesting that prepulse inhibition deficits may be linked to abnormal cognitive processes. Michael Koch (Ger) continued the discussion of prepulse inhibition by focussing more on the underlying neuronal substrate. He clearly discussed the neuronal circuitry involved in the primary startle reflex, as well as the presumed substrate for prepulse inhibition. However, he also provided evidence that, although the principal prepulse inhibition circuitry is most likely located in the brain stem, many forebrain structures (such as the prefrontal cortex and the amygdala) can modulate the prepulse inhibition, presumably by impinging upon the primary prepulse inhibition circuitry. Bart Ellenbroek (NL) described the role of genetic and environmental influences on information processing. He showed that rats pharmacogenetically bred for high susceptibility to dopamine agonists showed deficits in prepulse inhibition and latent inhibition. Moreover, he provided evidence that the phenotypical expression of this susceptibility was dependent on the early postnatal environment. Bob Oades (Ger) discussed another aspect of information processing, namely the conditioned blocking paradigm, in which subjects have to distinguish between relevant and irrelevant information. He showed that schizophrenic patients, especially paranoid schizophrenics, have clear blocking deficits, and these deficits were correlated with the thought disorder deficits in these patient. Helmut Schroeder (Ger) described the changes in rats chronically treated with phencyclidine. His data showed that both the behavioural (such as reductions in latent inhibition) and the biochemical alterations (such as reduced TCP binding in the hippocampus) depended on the mode of administration (pulsatile administration or through infusion).

Robin Murray (UK) gave the clinical introduction on the neuropathology of schizophrenia. He strongly argued that schizophrenia is not a neurodevelopmental disorder, but rather a disorder with a neurodevelopmental component. Factors close to the outbreak of the disease, such as stressful life events and/or drug abuse are also important components. He discussed the principal pathological findings in schizophrenia research. Or rather, he focussed more on the lack of pathological findings. Thus, although some studies have found significantly smaller hippocampi in schizophrenic patients (especially in sporadic cases with clear obstetric complications), they are no different from the hippocampi of non-schizophrenic children born prematurely (before week 32). Henk Groenewegen (NL) discussed the details of the neuronal circuits most likely involved in schizophrenia in his non clinical introduction. He focussed mainly on the interactions between the prefrontal cortex and the basal ganglia, showing, on the one hand several clearly segregated loops, such as those involving the orbitofrontal cortex and those involving the medial prefrontal cortex. However, on the other hand he provided clear evidence that the different loops are interconnected at various different levels of the organisation. Peter Danos (Ger) discussed his recent data on thalamic pathology in schizophrenia. He found significant reductions in the density of neurons in the ventrolateral posterior nucleus, but no significant alterations in other thalamic nuclei, including the mediodorsal or anteroventral nucleus. Shon Lewis (UK) proposed a completely new approach to studying the neuropathology of schizophrenia. Rather than focussing on the size of the brain, he proposed to investigate the shape. Although this would require a completely new of analysis, he provided the first data to show that schizophrenic patients indeed have differences in the shape of the brain (such as the pattern of gyri).

The fifth session concentrated on the neurochemical abnormalities seen in schizophrenic patients. For many years the dopamine theory of schizophrenia has dominated the neurochemical field. However, as Peter Falkai  (Ger) discussed in his clinical introduction, there is very little evidence that schizophrenia is accompanied by an overactive dopamine system. Moreover, it is unlikely that alterations in dopamine are responsible for the negative symptoms of schizophrenia. He proposed that the more fundamental abnormalities in schizophrenia are related to disturbances in neuronal migration, for instance in the entorhinal and prefrontal cortex. Presumably, these primary disturbances subsequently lead to abnormalities in the dopaminergic transmission. John Waddington (Ireland) gave an overview of the behavioural pharmacology of the various dopamine receptors. His basic conclusion was that drugs selectively acting of either the D3 or the D4 receptor were behaviourally virtually inert. Although some of the D3 antagonists did induce some behavioural effects (such as an increase in locomotion and sniffing), others did not. Moreover, the in vivo profile of these drugs was difficult to match with the  D3 binding efficacy. Uriel Heresco Levy (Israel) described his clinical experience with drugs affecting the glutamate system. He showed that glycine, which indirectly stimulates the NMDA receptor slightly improved negative symptoms, without affecting the positive symptoms. However, very high doses were needed (60 g/day). Other NMDA agonists, such as d-cycloserine or d-serine were also not very effective. Taken together, these data suggests that the current generation of NMDA stimulating drugs are not very effective. This may, however, be more related to the pharmacokinetic properties (poor penetration of the brain, only partial agonism) of these drugs than to the lack of effect of glutamatergic drugs per se. Beate Kretschmer (Ger) followed up on the glutamate hypothesis of schizophrenia, by discussing her data on the glutamate – dopamine interaction in the rat brain. She showed that there is a highly complex interaction between these two neurotransmitter systems, that depend on the brain region being studied (for instance the ventral tegmental area or the nucleus accumbens) but also on the type of glutamate receptor (for instance the NMDA or the AMPA receptor). Marco Riva (Italy) discussed the role of neurotrophic factors in animal models of schizophrenia, including the prenatal treatment with corticosterone and the maternal deprivation model. He showed that in both models there was a strong reduction in brain derived neurotrophic factor (BDNF) in the hippocampus. This reduction was seen both at the level of  mRNA as well as at the level of the protein itself. He also showed that stress, in itself significantly reduced BDNF in the hippocampus. These data are in agreement with previous clinical data that showed reduction in hippocampal BDNF levels in schizophrenic patients.


The final session of the workshop was dedicated to the neuro-developmental hypothesis of schizo-phrenia. The clinical introduction was given by Elaine Walker (USA). She first discussed some animal models (such as psychosocial stress and hypoxia) in relation to schizophrenia like deficits (such as hippocampal abnormalities and neuromotor disturbances). She further continued to discuss her results on a long follow-up study of children with schizotypal personality disorders, children with other personality disorders and normal children. It appeared that the patients with schizotypal personality showed many schizophrenia-like abnormalities early in life. Since schizotypal personality disorder is genetically linked to schizophrenia, it is likely that a number of these patients will eventually develop schizophrenia, and it will be interesting to see whether these differ from the ones that do not develop schizophrenia earlier in life. Andrew Foley (Ireland) next discussed the role of polysialylated-Neural Cell Adhesion Molecules (PSA-NCAM) in relation to animal models of schizophrenia. He showed that in animals reared in isolation, as well as in maternally deprived rats, the hippocampal levels of PSA-NCAM were significantly reduced. The same effect was seen in rats perinatally subjected to a period of hypoxia. On the other hand, rearing rats in an enriched environment led to an increase in PSA-NCAM. Since this form of NCAM plays a crucial role in plasticity, it seems that plasticity is comprised in these models of schizophrenia,. Frank Sams Dodd (Spain) discussed a number of different animal model specifically focussing on the neurodevelopmental hypothesis, including prenatal treatments (MAM, hypoxia or phencyclidine) and postnatal treatments (maternal deprivation and early ventral hippocampal lesions). He showed that prenatal treated with the mitosis blocker MAM or neonatal hippocampal lesions reduced social behaviour in rats. Jim van Os (NL) discussed, in his paper, the relationship between stress and schizophrenia. He showed that patients suffering from schizophrenia had a hyper-responsiveness of the stress system. When schizophrenic patients were subjected to a metabolic stress paradigm, they showed the largest plasma increase in homovanillic acid.

The workshop was closed by the first IGBP lecture, given by Michael Maes (NL). He discussed the relationship between psychiatric illness and the immune system. He clearly showed that depression was accompanied by increases in the monocytic and the lymphocytic arm of the  immune system. The situation in schizophrenic patients, he argued, is less obvious. Although alterations in both arms of the immune system have also been reported, they seem more secondary to the disease. His principal argument for this was that certain interleukins are known to induce depressive symptoms in non-depressed patients, but none induce psychotic symptoms in  non-psychotic patients.

Finally, a number of posters were presented during the workshop, ranging from very detailed neurochemical analyses of the effects of antipsychotics to the role of fatty acids in recent onset schizophrenia. Overall the meeting offered a good opportunity to bring together clinical and preclinical researchers in an attempt to give a overview of the state of the research in the broad field of schizophrenia. 
New Advances in the Understanding and Treatment of Addiction, University of Sussex, Brighton, 19-21 September 2002

posted 22.01.2003
by Paul Willner (meeting organizer)

This meeting was organized jointly with the European Behavioural Pharmacology Society, the third joint UK meeting of the two Societies: the first, held in Cambridge in 1992, was a large general meeting (a biennial meeting for EBPS; a summer meeting for BAP) ; the second was a Workshop on Depression and Anxiety held in Bath in 1992. Both of these meetings are remembered as having been extremely successful, and consequently, expectations of this Addiction workshop were high.

The meeting attracted just under 140 participants, with good attendance from both Societies, as well as from non-members, and a stellar cast of speakers. Sadly, two of the planned speakers, Mary-Jane Kreek and Nora Volkow, were prevented from attending by sudden emergencies, but both managed to persuade able colleagues - Stefan Schussman and John Gatley - to drop everything and rush across the Atlantic to take their place.

The meeting included four scientific sessions, together with an introductory overview (presented by Paul Willner), a concluding general discussion, a poster session, and a conference dinner - all for a ridiculously inexpensive all-in fee. Three of the sessions were organized primarily around psychological issues in addiction: persistence of, and loss of control over, substance use (Gene Heyman, Richard Hammersley, Trevor Robbins, Stefan Schussman); compulsive drug use (Gavin Phillips, Gaetano Di Chiara, Leslie Iversen, John Gatley); and relapse (Paul Davis, Yavin Shaham, Steve Tiffany, Barry Everitt). These sessions were intended to stimulate participants to think about the different psychological processes involved in addiction, and their respective neurobiological mechanisms. The fourth session, on novel approaches to the treatment of addiction (Dai Stephens, Robert West, Chuck O'Brien, Steve Higgins), was perhaps more conventional, from the point of view of both Societies. The poster session included over 60 contributions, arranged in six groups: rewarding effects of drugs of abuse (the largest group); behavioural sensitisation; tolerance and withdrawal; attention and social behaviour; stopping drug use; and neurochemistry and genes. The Workshop was accompanied by a Special Issue of Behavioural Pharmacology (Vol. 13, Issues 5-6), also devoted to New Advances in the Understanding and Treatment of Addiction, which includes the Abstracts of talks and posters presented at the meeting.

Forty of the participants completed and returned a feedback form, which asked for responses to scientific and administrative aspects of the meeting, scored on a 10-point scale (where 0 = worst ever, 5 = average, and 10 = best ever). Needless to say, the highest scores (median = 9) were awarded to Susan Chandler and Tammy Ward for the quality of the pre-meeting and in-conference information provided to participants. Participants rated the meeting very highly (median = 8) for the choice of speakers, the quality of presentations, and the balance of the meeting, and even higher (median = 9) for intellectual stimulation. (What more could an organizer wish for?) Participants' feedback forms also identified some obvious weaknesses of the meeting: discussions tended to be dominated by the invited speakers, so that audience participation was limited (median = 7); more time, and perhaps some wine, would have improved the poster session (median = 7); the venue left something to be desired (median = 7), and the less said about the catering arrangements the better (median = 5): though personally, I found the conference dinner acceptable!

This workshop was a pleasure to organize, thanks in large part to the active involvement of the scientific committee (Jack Bergman, Judy Pratt, Charles Marsden, David Nutt, and Dai Stephens), and the unfailing administrative back-up provided by the BAP office. We gratefully acknowledge financial support from Lilly (UK and USA), Merck Sharp and Dohme, The Wellcome Trust, Wisepress, and Wyeth. Overall, participants rated the meeting at 9 for the quality of the science, 8 for the social experience, and 8 for enjoyment: another successful meeting for EBPS and BAP, and another challenge to the organizers of future meetings - another joint EBPS/BAP in 2007, perhaps?