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Michael Dalili’s report from Wednesday morning:
Jeffrey Dalley started off this session on the last day of the 2014 summer meeting of the British Association for Psychopharmacology with his talk on animal models of dopamine and impulsivity. He described the curious phenomenon of the emergence of compulsive symptoms from dopamine agonists, including gambling, shopping, and hypersexuality. Impulse control disorders, or ICDs, occur in about 14% of Parkinson’s disease (PD) patients. He told us that risk factors for the development of ICDs include being male, young age at PD diagnosis, a premorbid history of drug abuse, history of depression, and novelty seeking behaviour. He also claimed that there tends to be a premorbid vulnerability for the development of ICDs, and noted their heterogeneous aetiology, given the multiple dimensions of impulsivity in PD. In fact, even in the absence of ICDs, PD has been shown to affect several modes of impulsivity. He looked at this in rats using a delayed discounting task, as those with impulsivity tend to undervalue delayed rewards and overvalue immediate rewards, regardless of medication status. Conclusions from his work suggest that impulsivity is a multi-dimensional construct that is co-morbid with PD and possibly independent of medication status. There are still various theories to explain the occurrence of dopamine agonist-related ICDs but there remains a considerable scope for developing new therapies to modulate the spectrum of impulsivity/compulsivity endophenotypes.
The next talk of the session was by Celeste Napier on modeling impulse control disorders and PD comorbidity. She started off by also describing the risk factors of ICD, which include being treated for PD with a dopaminergic agonist such as Pramipexole. She discussed rat models of early stage PD, describing the neural and motor pathology associated with the disorder, such akinesia and resting tremors in humans being homologous to difficulties seen on the forepaw adjustment stepping task in rats. She presented her work using this task in rats, revealing that pramipexole reverses robust stepping deficits in lesioned rats in a dose-dependent manner. She went on to explain her work using a delayed discounting model in rats that uses intracranial self-stimulation as reward, avoiding the problems associated with using food rewards and allowing for small and large reinforcers to be used. She discovered this is a very efficient way of teaching rats to do an operant task, as they learned almost immediately. What she found was that pramipexole increases ‘risk tasking’ in rats at the end of 14 days. As probability of a large reward decreases they switch to the getting a certain small reward. But after two weeks of pramipexole, animals will still stick to the large reward even when probability goes down. Therefore she concluded that the drug increased risk-taking behaviour in the rats. Her take-home message was that this protocol provides a useful model of PD and ICD comorbidity.
The next speaker was Paola Piccini whose talk was titled “Dopamine, impulse control disorders and Parkinson’s disease: PET imaging studies”. She started by describing PD particularly as a motor disease, with the death of dopaminergic neurons in the substantia nigra and caudate areas of the brain. She described how the treatment for PD, Dopamine Replacement Therapy (DRT) has not changed much over the years and that we still have no cure for the disorder. She went on to describe Dopamine Dysregulation Syndrome, or DDS, and its diagnostic criteria, explaining that these patients expressed the need for increasing doses of DRT in excess of those normally required, showing a withdrawal state if the drug is withdrawn. She explained that the prevalence of DDS in the general PD population is unknown, with a UK specialist clinic reporting 4% while an Italian group reported 3.4%. She went on to describe the epidemiology of ICDs, identified in about 14% of this population. This includes about 5% who pathologically gamble, 3.5% who engage in compulsive sexual behaviour, 6% who are compulsive buyers and 4% who have binge eating disorder, with 4% of patients having two or more of these problems. She explained that it is very difficult to predict which patients will go on to develop ICDs, especially given that they need to be on medications, thought to be the greatest risk factor. She presented work looking at rewarding imagery and dopamine levels, and concluded by saying that subtypes of ICDs may have partially different mechanisms, as some ICD subgroups were more susceptible to visual reward associations than others.
The last talk of the day was by Valerie Voon titled “Dopamine, impulse control disorders and Parkinson’s disease: Cognitive and functional imaging studies”. She started by describing the dopaminergic system, explaining that dopamine agonists act on both pre- and post-synaptic receptors, with a preference for D3 receptors. She stated that PD is really understood to be a neuropsychiatric disorder. She explained that she would focus on pathological gambling, hypersexuality, binge eating, and compulsive shopping tied together, as in all conditions patients feel preoccupied, are unable to control urges, have persistent thoughts, and they all result in serious consequences. She noted that the frequency of ICDs in PD is not so different from the frequency in the general population, but that the timing of onset is very different. She stated there is clear evidence of an association between ICD in PD and dopamine agonists. For instance, Levodopa, a principal medical treatment for the symptoms of PD, is an independent risk factor for these behaviours on its own. However, there is less of a clear association between dopamine agonist dose and these associations. Therefore she was interested in why we see this occurring in a subset of this population and whether there was an Interaction with individual susceptibility. Similarly, the role of PD and these behaviours is unclear, as the disorder may be protective against or facilitative to these impulsive and risky behaviours. She conducted studies to investigate subgroup differences, trying to tease apart what is different about specific subgroups and why patients develop one behaviour over another. Among her findings, she stated that PD patients who are compulsive shoppers and gamblers make more impulsive choices than binge eaters and hypersexual individuals. Therefore she concluded her talk by claiming that subgroup differences between PD patients relate to gender, novelty seeking, and impulsive choice. This brought the Wednesday morning session to a close.
Claire Mokrysz’s Wednesday morning report:
One of the three final symposia on Wednesday morning was "The adolescent brain- A key stage in the development of psychiatric disorders?" chaired by Sarah Bailey.
Sarah-Jayne Blakemore of UCL kicked off the session by discussing her work on risk-taking and social development in adolescence. Adolescence is defined as the period of life starting at puberty and ending when an individual gains a stable and independent role in society. We heard about several strands of evidence demonstrating that the brain, particularly frontal regions, undergoes a period of refracted development spanning adolescence. For example we know frontal grey matter volume and synaptic density in the prefrontal cortex (PFC) both increase throughout childhood, peaking around the age of puberty, before steadily declining with age. Sarah also discussed a neat study in which adolescents and adults completed a computerised driving task. There were no differences between the groups in risks taken when the participants completed the task alone; however when a friend stood and watched the participant complete the task, adolescents showed considerably greater risk taking than the adults. This demonstrates that while adolescents are not necessarily default risk takers, in certain social situations they will take more risks. It has therefore been suggested that adolescents are not irrational in their risky decisions, but that the factors influencing a decision may be different for them compared to adults.
We next heard from Debra Katzman of Toronto who discussed adolescent-onset anorexia nervosa and the effects seen on oestrogen. Anorexia nervosa has the highest mortality rate of any psychiatric disorder, with 5.86 deaths in 1000 patients per year. Debra discussed the negative impact of starvation on oestrogen, and the effects of decreased levels of circulating oestrogen on the female adolescent body. Reduced oestrogen levels are related to bone mineral density deficits, cognitive deficits, and mood problems. These problems in adolescence can have a long-term impact, for example bone density can remain low throughout an individual's life, and cognitive impairments are associated with worse outcomes.
After a coffee break Ian Goodyer of Cambridge discussed psychiatric disorders in adolescence. Incidence of many psychiatric disorders peaks in adolescence. The pattern of incidence is associated with limbic system neuromaturation outpacing prefrontal development, creating a "neuromaturational gap". As frontal regions then mature in later adolescence the incidence of new psychiatric disorders also decreases. Ian then suggested that experiences at different points in development can exert unique effects on neural structure, and suggested that mental illnesses may not be distinct disorders, but may share a core set of neural characteristics that increase risk of any disorder, and a set of specific deficits that relate to a specific pattern of symptoms. We may therefore have more success understanding mental illness if we look at the relationship between patterns of experience, behavioural traits and neural substrates.
Lastly we heard from Gillian Brown at St Andrews, who discussed her work in rodents assessing the role of gonadal hormones on behaviour. Sex differences in the prevalence of some anxiety and mood disorders emerge during adolescence, a period of time in which we see large fluctuations in gonadal hormones, which may be impacting upon susceptibility to these disorders. To explore this Gillian has run a series of experiments with rats assessing the emergence of sex differences in anxiety-like behaviour in adolescence and the role of gonadal hormones. This work has shown that if adolescent male rats are not exposed to testosterone in the adolescent sensitive period, they tend to display increased anxiety-like behaviours which are more typical of female rats. This work therefore has important implications for understanding the emergence of anxiety related disorders in human adolescence.
Another exciting symposium from BAP 2014. Adolescence has only been recognised as such an important stage of development in the past few decades, so it was great to hear such a diverse selection of research that is revealing more about the adolescent brain.
Meg Fluharty’s Wednesday morning report:
On Wednesday morning, I attended ‘’Tobacco addiction in schizophrenia: a translational investigation’’ co-chaired by Victoria Wing and Mohammed Shoaib. Huib Mansvelder gave the first talk, on nicotinic receptor modulation in both rodent and human brains. Mansvelder discussed the relevance of layer-dependent nicotinic receptor expression in the human and rodent brain, with different layers containing different nicotinic receptors (NaCHRs). Smoking results in both NaChR activation and desensitisation. NaChRs in human layer 1 and 2 interneurons displayed mixed responses, and NaChR activation turned LTP to LTD in layer 2 and 3 neurons. Additionally layer 6 Pyramidal neurons were activated by NaChRs, which changed the responses in these neurons. Mansvelders’ talk displayed how layer dependence in neurons altered plasticity, and different subunits are differentially sensitive to sensitisation.
Mohammed Shoaib gave the next talk on the use of concurrent choice procedures following sub chronic ketamine exposure in rats. Shoaib discussed how intra-pre-frontal cortex nicotine can restore ketamine-induced deficiencies in working memory (a rodent model of some aspects of schizophrenia impairment). Shoaib tested nicotine self-administration in ketamine treated rodents, initially finding little difference, until they were provided with alternative sucrose reinforcers. Shoaib found that at day 1 there was large variation between preference in sucrose and nicotine, but by day 3 the ketamine treated rats were preferentially choosing nicotine over sucrose at a higher rate than the control animals. Shoaib’s findings suggest the high prevalence of tobacco smoking in schizophrenia may represent self-medication to restore cognitive deficits, rather than increase the subjective feeling of satisfaction.
Next, Victoria Wing discussed using varenicline to treat tobacco addiction in schizophrenia by targeting the cognitive deficits in the disease, as there has been emerging evidence of cognitive benefits in both patients and controls using the drug. Wing found that patients had heavier smoking topography compared to controls, and tobacco abstinence impaired visuospatial working memory in patients, but not controls. Varenicline reduced craving induced by overnight abstinence in patients and controls. Additionally, varenicline attenuated tobacco-withdraw induced visuospatial working memory deficits in patients with schizophrenia. Wing concluded by suggesting that tobacco withdrawal syndrome has specific features in schizophrenia, and that the mechanism by which varenicline aids smoking cessation may differ in schizophrenia.
Elliot Hong gave the final talk on brain circuits which link schizophrenia to high risk of cigarette smoking. Hong investigated the functional connectivity of brain regions in smokers, finding the dorsal anterior cingulate cortex (dACC)-striatum/ extended amygdala circuit to be associated with addiction severity. This circuit was also related to genes associated with nicotine addiction (Asp398A of CHRNA5, part of a cluster of nicotine receptor genes), and similar patterns of activation in schizophrenia. Hong discussed how the dACC circuit is affected by schizophrenia and nicotine, both independently and additively. Hong concluded by stating one or more brain circuits linked to schizophrenia may overlap with those associated with a genetic predisposition to nicotine addiction, and by using a brain circuit based explanation we can account for genetic, environmental, and mental illnesses which contribute to nicotine addiction.
Suzi Gage attended the post-doctoral symposium and the award winner’s oral sessions on Tuesday. Here are her thoughts:
I attended the post-doctoral symposium, which this year was themed around understanding vulnerability for treatment improvement. Bianca Jupp from Cambridge kicked off with a discussion about rodent models of impulsivity, and how they can be used to inform neurobiological mechanisms of risk of addiction. She discussed research looking at the individual differences in rodent impulsivity, rather than inducing impulsivity using knockout models, and how this might be more clinically appropriate for translational research of this kind. The research selected rodents who performed at the extremes on an impulsivity task, and compared them. Impulsive rats self-administered more cocaine, did so more compulsively, and had increased vulnerability to relapse. She mentioned similar research, which has shown these findings for alcohol and nicotine as well.
She showed evidence that drugs of abuse actually decrease impulsivity in this highly impulsive animals. She put forward what she referred to as a ‘provocative hypothesis’; namely that the increased stimulant use seen in impulsive individuals might be self-medication. Although she pointed out that this is hard to test. She then presented elegant experiments trying to get at the mechanisms that may be involved. She showed that dopamine D2 receptors showed reduced binding in a brain area called the ventral striatum. Using PET scanning, research showed that cocaine administration in high-impulsive rats both reduces impulsivity, and increases D2 receptor availability. Not only that, but animals with lower D2 binding before being given cocaine showed a greater increase. She pointed out the implications of these findings for ADHD therapy, and went on to discuss a similar study administering an ADHD medication similar to cocaine (methyphenidate), which showed similar associations. She lastly presented structural findings which suggested alterations affecting the function of GABA in high-impulsive animals. Her conclusions were that causation is still unknown, but that these potential mechanisms are worthy of further investigation.
Martin Egeland spoke next, on inflammation and depression. He presented findings from a ‘multiple hit’ animal model, where rodents are exposed to early life inflammatory insult, then neurogenesis impairment at adulthood. Finally, later life stresses, in the form of unpredictable chronic mild stress, are imposed upon the animals.
His study investigated cytokines (small proteins which regulate inflammation) after the early life insult, and behavioural measures after the neurogenesis impairment, and the later life stressors. He found that an early life inflammatory insult affected future response to the presence of cytokines. The behavioural assessment that occurred after the neurogenesis impairment suggested that neurogenesis disruption impacted negatively upon rat behaviour in a tail suspension task, a behavioural model designed to mimic depression.
Finally, the ‘triple hit’ of early life inflammation, early adulthood neurogenesis disruption and later life stress was investigated. The results suggested an additive effect of adult impact on the vulnerability caused by early life inflammation. For example, ‘triple hit’ animals showed the worst outcome on coat score (a measure of the healthiness of their grooming behaviour) and put on the least weight – both indications of poor mental health in rats. However, Egeland added a note of caution, which was that multiply affected animals showed hyper-locomotion, which may have influenced the findings from some of the other behavioural tasks. He concluded that inflammation sensitization early in life may predispose the animals to risk of depression and anxiety, and suggested that future research should try and overcome the hyper-locomotion, either by working out why it may occur, or finding paradigms to assess depression or anxiety that will not be disrupted by the behaviour.
Annamaria Cattaneo from London was the third speaker, presenting neat work on the role of epigenetics on stress-related changes in the brain, which might increase the risk of psychiatric disorders. She pointed out that although it’s known that early life stress, inflammation and stress response are linked, and that this might persist over time and make individuals more vulnerable, the mechanism that forms this ‘bridge’ is not known. She posited that epigenetics might play a role, either via DNA methylation, or changes in microMRA. She discussed research in to this in animals and humans. Firstly, a prenatal stress model in rats was used, which suggested SGK1 (a gene involved in stress-induced reduction of neurogenesis) might be key here. She showed cells labeled with markers of neurogenesis. Cells treated with cortisol (a stress hormone) showed reduced neurogenesis. This effect was abolished when they were cotreated with an inhibitor of SGK1. She showed evidence that SGK1 levels were increased in animals whose mothers were stressed prenatally and also in the blood of humans with a history of childhood trauma, or who were depressed. Even more elevated levels were seen in depressed patients who also had a history of childhood trauma.
Finally, she discussed epigenetic evidence, which suggested an increase in SGK1 methylation in prenatally stressed rodents. Hyper-methylation usually predicts a reduction in gene expression, rather than an increase as seen here. However, when she took microRNA modulation in to account, this explained the elevated levels of SGK1 seen in stressed and depressed rodents and humans. She concluded that these changes in biological processes might explain the increased vulnerability to psychiatric disorders seen in those who experience early life stressors.
Finally in this session, Martina Di Simplicio gave a fascinating talk about the effect of SSRIs on those at risk for psychopathology, which could potentially explain why patients might initially report that SSRIs actually increase their anxiety, before a positive effect of the drugs is seen. She discussed findings suggesting that SSRIs might work by reducing negative biases, and evidence that a reduction in the hyper-reactivity of the amygdala to fearful stimuli might be a mechanism for this. However, she noted that in clinical practice results are still much more varied, with some patients failing to respond, and some showing initial increases in anxiety.
In order to investigate this, they recruited a neurotic population (those with low mood, high anxiety, poor social functioning). Neuroticism is a risk factor of psychopathy, poor life quality and depression, and there is a suggestion it might be associated with a poorer response to antidepressants. They investigated what 7 days of either citalopram (an SSRI) or placebo had on emotional faces tasks.
They found that a week of SSRIs made neurotic individuals show an increased brain response to fearful faces. When they specifically looked at the amygdala, an increased response to all faces was seen, regardless of whether the faces were happy or fearful. Interestingly, the increase in response in the amygdala was correlated with reported lower levels of calmness in the group given SSRIs.
A second study used the same conditions, on the same population, but investigated how the participants explored the faces, using an eye-tracker. They were also asked to identify the emotion present this time. Martina and her colleagues found that those on SSRIs looked for longer at the eyes of the faces shown. SSRI administration was also related to better accuracy at identifying positive versus negative emotion in the faces. Their emotion recognition performance was predicted by how long they maintained gaze over the positive faces in the other tasks.
While these results might seem a little counter-intuitive, Martina had a really neat theory for what they might mean. If neurotic people are avoiding negative faces due to biases in their behaviour, then in the short-term, SSRIs might lead to them stopping avoiding the faces. This might initially be associated with increased anxiety, as they see these fearful faces more rather than avoiding them, but in the long term increased exposure to them could contribute to a reduction in negative biases, and therefore potentially resolve their depression and anxiety symptoms. A great theory, which her lab intend to investigate further.
In the afternoon, I attended the BAP Psychopharmacology Award Winner’s presentations. There are two non-clinical, and two clinical awards presented each year. This year, Oliver Robinson was awarded the junior non-clinical award, for his research on the dorso-lateral pre-frontal cortex’s connections with the amygdala, and how this connection might provide a neuropharmacological target for anxiety disorder treatment and diagnosis.
He presented three studies, which combined neatly to investigate this connectivity as a mechanism for depression and anxiety, using neuropsychological tasks that measure negative bias, known to be affected in depression and anxiety.
Firstly he induced negative bias in healthy people, using a ‘threat of electric shock’ task, and showed this was associated with increased connectivity between the those regions. He suggested this could be an adaptive mechanism: increased awareness of negative stimuli when anxious could be advantageous.
His next study demonstrated how this adaptive trait might become maladaptive in anxious patients, who showed the same connectivity as seen in the ‘threat of shock’ task, but without any threat present. He suggested this might be evidence that this adaptive trait has become permanently ‘switched on’ in anxious patients.
Finally, he presented evidence using a tryptophan depletion paradigm, which can induce symptoms of depression and anxiety, and globally lowers serotonin in the brain. This lowered serotonin increased the connectivity in this brain area, implicating it here. He concluded by mentioning future plans to assess the impact of SSRIs on the circuit, and pointed out that this could provide a target for new therapeutic models and interventions.
Ulrich Ettinger, the winner of the senior non-clinical award, presented next on human models of schizophrenia. He discussed new human models of schizophrenia, which included people on the schizotypy sprectrum, using ketamine to model schizophrenia, and sleep deprivation. He then investigated the effect of these models on biomarkers for schizophrenia; namely an anti-saccade eye-tracking task, smooth persuit eye movements, and pre-pulse inhibition (a brain response measured using EEG). He showed that all three models showed impairments in the biomarkers he investigated. When the anti-psychotic drug risperadol was given, in the hope that it would reverse these effects, for the most part it was ineffectual, although there was some evidence that it might have an effect in people who scored high for schizotypy.
He concluded a fascinating talk with a philosophical question: what do we expect from our models of schizophrenia? Should they be a small-scale replica, or would we be better off modeling one aspect and fully understanding it, before trying to consider something as complex as schizophrenia as a whole?
Michael Bloomfield from London was the winner of the junior clinical award, and presented on the effect of dopamine on long-term cannabis users. He hypothesized that the association between cannabis use, psychosis and apathy might be mediated by dopamine, which would increase the risk of psychosis via aberrant salience processing. If this was the case, cannabis users might be expected to have increased dopamine synthesis capacity. However, he found the opposite, namely that heavy cannabis users showed decreased dopamine synthesis capacity. He also investigated tobacco use, which suggested that the effects seen were unlikely to be driven by tobacco smoking. He concluded that his findings questioned the hypothesis that cannabis use induces psychosis risk by inducing the dopamine alterations seen in schizophrenia.
The final presentation of the session was given by Oliver Howes, the winner of the senior clinical award. This talk was also on dopamine, and more particularly on how we should start looking at the interactions between the individual systems and processes affecting mental health that have been developed in the past decades.
He used the psychosis prodrome to correlate various phenomena known to be related to schizophrenia, in order to try and understand their associations and involvement in the development of the disorder. He showed neat evidence that negative effects on verbal fluency, and dopamine function, thought to be independently related to schizophrenia, are correlated in people with schizophrenia prodrome who go on to develop the disorder.
He presented other data showing correlations between amygdala response to fearful faces and 5HT1a receptor availability (known to be lower in those with depression), suggesting that these associations between factors previously considered to be independent are being found for other disorders too.
He concluded by saying that these relationships provide hope that we are tapping in to the underlying processes of disease development and maintenance. If there are underlying processes, there are things that we can manipulate to investigate. A positive end to a great set of prize-winning talks.
On Tuesday, Meg Fluharty attended the ‘Chicken and Egg’ morning session, and ‘Understanding Cognition and Emotion’. She’s summarised the sessions here:
On this sunny Tuesday morning, I chose to attend ‘’Chicken and Eggs: Seperating cause and effect in drug addiction,’’ co-chaired by Luke Clark and Boris Quednow. Quednow started off the symposium with a talk on cognitive dysfunctions in cocaine users. He discussed a longitudinal study of stimulant users in which dependant users displayed strong cognitive impairment, particularly in working memory, but recreational users also displayed deficits in attention. Stimulant users were less altruistic, had less social contacts, and reported feeling less supported by social networks. However at 12 month follow-up individuals who decreased their stimulant use had increased performance in all cognitive domains. He concluded that this suggests both social and non-social deficits may be in part drug-induced and reversible.
Next up, Tommy Pattij discussed impulsivity as a vulnerability factor for addiction. He suggested that impulsivity may act on several different stages of the addiction cycle; from increased drug seeking, to loss of control into compulsive drug use, and relapse once in the withdrawal stage. Pattij detailed how animal models have been used to understand the relationship between trait impulsivity and drug seeking behaviour. For example, high impulsivity predicts cocaine, nicotine, and sucrose seeking, but does not predict heroin or alcohol seeking behaviour.
Karen Ersche spoke about a systemic review of drug addiction, in which she examined multiple known side effects, and discussed whether these were due to drug abuse or present prior to use. Ersche examined fluctuations in body weight in cocaine users compared to non-addicted siblings. The findings were interesting, suggesting that cocaine use was associated with a reduced hedonic appreciation for food, but participants still valued it and were willing to pay just as much or more than controls for it. Chronic use was also associated with uncontrollable eating, which was associated with levels of impulsivity. Additionally, their non-affected siblings displayed higher BMIs than controls, which may suggest a predisposition to loss of control.
Finally, Marco Leyton discussed vulnerability to addiction using dopamine studies in humans. Leyton found that putting individuals in a low dopamine state did not affect the pleasure elicited by cocaine use, alcohol or smoking. However, a low dopamine state did affect how much the individual was willing to work for the reward. This suggests that across the stages of addiction, dopamine plays a role in drug seeking. Leyton found a clear effect of dopamine sensitisation in humans after repeated amphetamine administration. Additionally, Leyton discussed the importance of a cue related environment for drug-seekers, finding that an increase of drug related cues increased the dopamine sensation, and the absence of cues may result in dopamine inhibition.
This afternoon, I attended the short orals session ‘Understanding Cognition & Emotion,’ chaired by Catherine Harmer. Juilette Tobias-Webb started off the session with a talk on illusions of control in a novel laboratory task. Illusion of control is the tendency to overestimate the degree of control in chance situations; for example in gambling individuals throw dice harder for large numbers and softer for small numbers. In a study Tobias-Webb conducted, she found subjects were willing to pay more than 50% of the time to exert irrelevant control in a game of chance. Additionally, participants felt more confident when they exerted control. This effect was found to generalise to non-gambling scenarios.
Next, Catherine Charpentier discussed making decisions when emotions run high. For this talk she focused on ‘loss aversion’, or the tendency to be sensitive to monetary losses, and questioned whether there was an emotional modulation of loss aversion. Charpentier found a negative correlation between low trait anxiety scores and an increase in loss aversion. However the opposite was true for high trait anxiety. She also examined fMRI responses in the functional connectivity between the ventral striatum and amygdala, and found similar results to her behavioural data, with functional connectivity between the two areas in low trait anxious individuals, but not high trait anxious. Charpentier raised the question as to why this effect was only seen in low trait individuals, suggesting that perhaps it was an adaptive harm-avoidance process, or a reduced sensitivity to pathological anxiety.
Michael Browning presented next on learning abnormalities in anxious individuals. Browning discussed that learning required balancing incoming information with what is already known, and knowing what weight to put on this incoming information, so perhaps it is the learning rate which anxious individuals struggle with. Browning found that anxious individuals had reduced learning rate flexibility to changes in environment volatility, and reduced responsiveness to a measure of norepinephrine (pupil diameter). Browning concluded by suggesting that inability to adjust learning rate may be one mechanism underlying the difficulty in learning about aversive outcomes in anxiety.
After a bit of technical difficulty, and some joking words of wisdom (don’t close the laptop immediately after you load your talk!) Daniel Campbell-Meiklejohn gave the final talk on monoamine effects on social learning. Campbell-Meiklejohn focused on conformity in the rating of trustworthiness of faces after giving individuals placebo, methylphenidate, or citalopram. He found that individuals given citalopram initially rated faces lower, and were more likely to conform to reduce trustworthiness ratings. Campbell-Meiklejohn suggested serotonin may mediate social influence by adjusting engagement with aversive information regardless of whether socially or non-socially derived.
Michael Dalili attended the symposium on genetic pathways in psychosis, and the short orals session on developing depression.
Kristen Brennand started the day’s session with her talk on the promise of using human induced pluripotent stem cells in schizophrenia. She began by remarking that it is extremely hard to get live human cells with the disease, and as such researchers haven’t been able to do comparisons of these cells in the lab. However, you can do this using stem cells, or more specifically hIPSCs cells. Using these cells allow researchers to produce limitless live diseased human NPCs, or neural progenitor cells, and neurons. She spoke about identifying cellular phenotypes and correlating schizophrenia candidate genes to RNA expression levels in NPCs and neurons. She expressed her interest in how schizophrenia sufferers’ neural cells are different from those of controls, and questioned why they are different. She discussed the relevance of reduced rabies transmission to schizophrenia, describing reduced neuronal connectivity in schizophrenic hiPSC neurons. She described that there may be decreased branching in schizophrenic neuronal cells, seen in rodents using hiPSC. She also said that the number of active neurons is down in a schizophrenia culture and that the aberrant gene expression characteristic of schizophrenia neurons exists in NPCs before neuronal differentiation. In fact, she stated that even before a synapse is present, synaptic pathways are perturbed, affecting the whole neuronal migration network. She claimed there seems to intrinsic failure of schizophrenic cells to migrate as far as control cells and stressed the importance to consider the protein changes in schizophrenia NPCs, who also have increased oxidative stress resulting in increased inter-cell variability.
Stephen Lawrie continued the session which his talk titled “The impact of schizophrenia risk genes upon brain function”. He started by talking about the landmark schizophrenia human brain imaging studies around 1974 and described the work identifying family history during the 80s and 90s. He discussed the genetically acquired abnormalities in schizophrenia from early in life and the additional changes at onset, as well as the differences between being at risk and having the disorder. He suggested there are anatomical, functional, and multi-modal differences in the relatives of those with schizophrenia as well. Therefore the approach was to take some of the best genetic hits for schizophrenia and relate them to the imaging abnormalities in high risk cohorts, given schizophrenia’s high familial risk. He described this type of work in bipolar disorder before describing work published today identifying 108 independent SNPs conferring increased risk for schizophrenia. He then spoke about a large Scottish mental health neuroimaging study involving the DISC1 gene. He mentioned that the dorsolateral prefrontal cortex is a heritable region of schizophrenia abnormalities, primarily involving glutamate, not solely driven by psychosis. He also discussed robust results in the corpus callosum as well as reduced functional connectivity between the frontal lobe and caudate regions of the brain. He went on to talk about work using data from the Edinburgh High Risk Study to identify strong predictors of risk to develop schizophrenia.
The next talk was by Nick Brandon from AstraZeneca on translating the schizophrenia genome. He first described the recent launch of the “openinnnovation” portal allowing the acquisition of compounds for researchers in the context of collaborations. He stated that over the last 30-40 years, drug discovery has been much more difficult, with many more hurdles to getting the drug to market, as drugs must now be differentiated from standards of care on the market and must be made reimbursable. He explained that late-stage failures for schizophrenia drug discovery illustrate the challenge of achieving efficacy, resulting in questions about why the drug failed. Therefore they attempt to use human genetics in these trials and to understand the genetic architecture of schizophrenia, known to be highly heritable. Alone, these genes have modest effects, and therefore understanding them together is the challenge. The key is to know what targets and pathways to go after and to study rare variants and mutations researchers really need to study the family genetic information. He described the lessons learned from DISC1 gene studies and emphasized lessons learned from Alzheimer’s studies; namely that researchers shouldn’t ignore things simply because they are not at genome wide significance. He stated there are several hypotheses for a pathological mechanism from DISC1 and that mapping DISC1 interactions has been of tremendous value for generating molecular hypotheses. He stated that his work has focused on NMDA and GABA-A receptors more recently, going into more detail about his findings such as knocking out the DISC1 gene shows up-regulation of NMDA receptors.
Gerome Breen concluded the session with his talk titled “Understanding the genetic basis of psychiatric disorders: Beyond descriptive syndromes to shared biological pathways”. He began by stating that the overall heritability of psychiatric disorders is very high, with many of the estimates higher than those for robustly diagnosed physical disorders. He emphasised that uncovering specific genetic risk factors proved nearly impossible with candidate gene methods and that a single candidate gene would be largely undetectable in sample sizes below a couple of thousand individuals. In addition, single candidate gene studies do not allow for important statistical corrections. A Genome-wide Association Study, or GWAS, acts as a content capture tool by assaying the whole genome, allowing researchers to capture a lot of information. These studies have allowed researchers to develop an increased understanding of numerous genetic disorders. He stated that researchers can confidently say that GWAS does work but not in a simple way. However, he claimed that GWAS are infinitely better than candidate gene analysis studies. He discussed work driven by the Psychiatric Genomics Consortium, describing sample sizes increasing over time, often proportional to the amount of funding a disorder gets. As an example of the progress made in the field, he told the audience that in 2011 schizophrenia only had 5 hits while the aforementioned study published today has identified 108 hits for schizophrenia. He emphasized the need to push to enlarge sample sizes in GWAS as much as possible. He went on to discuss work on biological pathway analysis, including numerous methods and pathway databases used, with some overlap across bipolar disorder, depression, and schizophrenia. He discussed conducting a pathway level meta-analysis across disorders, stating it may be more powerful than conducting a SNP meta-analysis. He concluded his talk by discussing the advantages of using genetic data, ending a very interesting and informative morning session.
Enrica Fantini started off the afternoon session of short orals with her talk “Exposure to maternal childhood abuse and depression in utero: Effects on neonatal behavioural regulation and the hypothalamic-pituitary-adrenal (HPA) axis”. She began by telling the audience that adverse experiences of childhood increase chances of developing depression in adulthood, especially in vulnerable periods like pregnancy. Her focus is on psychiatry research and motherhood, and she told us about the “Pram Study” she conducted where they tested healthy and depressed pregnant women with or without a history of childhood abuse from the 25 week gestation point to 1 year postnatal. They collected data on maternal abuse, maternal mood, neonatal behavioural assessment and neonatal salivary cortisol. She then went on to talk about her findings, focusing on the neonatal work. Babies from women who were depressed, with a history of child abuse were hyper-vigilant and silent compared to the other babies, seemingly “shut down” behaviourally. These babies therefore showed signs of behavioural and physiological dysregulation. Furthermore, her salivary data suggested there is a correlation between the behavioural and physical responses of these babies. She ended by calling for doctors and nurses to be more aware of the childhood histories and current mental health of women in their care.
Next Lesley Cousins continued the session with her talk asking the following question: why do we prescribe antidepressants to teenagers? She started by stating that depression during teenage years is a big problem clinically and in public health terms, with the risk of incidence increasing throughout adolescence. In fact, many go on to develop a lasting condition through adulthood and are at risk for comorbidities. She presented the NICE guidelines for adolescent depression, which is quite anti-psychotherapeutic, with antidepressants as a second line of treatment when talking therapies fail, meant to be given in combination with talking therapies and only for moderate to severe depression. However, she was interested in why some adolescents were prescribed antidepressants and others were not. She looked at several possible factors such as MDD severity, quality of life or functional impairment, hazardous behaviour and gender differences. Her findings revealed that predictors for prescribing antidepressants depended on gender, where males were given medication based on their depression severity and females received antidepressants if they were at greater risk of self-harming behaviour.
Camilla Nord continued the afternoon with her talk titled “Exaggerated loss-specific Pavlovian-instrumental transfer in unmedicated major depression”. She started by telling the audience that depressed patients typically show a hyposensitivity, or a decreased response, to positive feedback, while they exhibit hypersensitivity, or an increased response, to negative feedback. Testing both patients and healthy controls, she used a Pavlovian-instrumental transfer task to test active or inhibitory behaviour associated with affective, environmental, object, or people cues. Using a go/no go type task, where approaching was responding to keep a desirable item and withdrawing was withholding a response to retain the item, she found a three-way interaction between group, withdrawal or approach, and go or no go bias. During a phase of the task associated with no gain, she found increased “withdrawal go” actions in patients and a decrease in “approach go” actions in patients, and her results also revealed that patients with more severe depression had a stronger go bias. She concluded by stating that quite a lot is known about the depression phenotype, global abnormalities, and how negative life events can impact the development of depression, and she believes this concept of disrupted Pavlovian transfer is part of how the magnified influence of aversive cues can affect depression and behaviour.
The last talk of the session was by Beata Godlewska with her talk titled “Early changes in neural response to emotional stimuli predict clinical response to SSRI treatment in depression”. She started by explaining to the audience that depression has a lot of burden at the individual and economical level and as of yet we have no predictor of response to medication. She then described the negative biases in emotion processing common in depression, and that negative thoughts precede low mood, resulting in reduced behaviours, all reflected by what is happening on the neural level in depression. From neuroimaging, we know that depressed patients typically have increased activation in the amygdala to fearful faces. She described that while antidepressants rapidly affect serotonin levels, it takes a few weeks for patients to report a difference in their mood. That is because while patients start to perceive the world in a more positive way early on in treatment, these perceptions must be relearned in a new, positive environment, consistent with the proposed cognitive neuropsychological theory of antidepressant action.
She was interested in answering the following question: can we tell who will respond to treatment on the basis of this early change in neural response to fearful faces? In a study where depressed patients either received an antidepressant for 6 weeks or placebo, she found that while ratings of depressive symptoms were almost the same at baseline and 7 days into treatment for both responders and non-responders, there was a pronounced difference in neural response across several brain areas including the thalamus, left amygdala, and insula. Therefore her findings suggested that early changes in neural activity preceded and predicted clinically significant changes in depressive symptoms and was not dependent on concurrent mood change. She claimed that this might provide an early neural biomarker of clinical response to antidepressant treatment in depression, with important implications for treatment. Following her talk the very interesting afternoon session drew to a close.
Claire Mokrysz attended a session on cannabinoids, and reports on Tuesday’s poster session:
Tuesday morning began for me with Val Curran's symposium "Cannabinoids in psychiatry: current understanding and future treatments". Val opened by saying how relevant and timely the symposium is considering the worldwide developments in cannabis legislation in recent years. We then heard from 4 great speakers who work with cannabinoids in a variety of different domains.
First up was Roger Pertwee of Aberdeen, who has pioneered research into cannabinoid receptors and the many different phytocannabinoids that can exist in any one strain of cannabis. Since the early '90s when cannabinoid receptors CB1 and CB2 were discovered, followed closely by the discovery of endocannabinoids and the endocannabinoid system, Roger has been exploring this exciting field. We heard about the wide variety of cannabinoids that are slowly being characterised and explored, and the therapeutic potential of these chemicals. For example the cannabinoid THCV which activates CB2 receptors and blockades CB1 may have a role in anti-obesity drugs since CB1 blockade is known to reduce food intake. Interestingly while cannabis is associated with increased risk of psychosis, a number of the cannabinoids Roger discussed, including THCV, CBD and CBG may in fact have antipsychotic properties.
Next up was Val Curran of UCL, discussing her work into the cannabinoid CBD. There is a growing body of evidence suggesting CBD may be protective against the harmful effects of THC, the cannabinoid associated with 'the high' from using the drug. Val highlighted how over the past decade the cannabis market in the UK and many European countries has become increasingly dominated by skunk, which contains high levels of THC and low or non-existent levels of CBD. THC is implicated in the addictive properties, psychotic-like symptoms and cognitive impairment related to cannabis, suggesting that these available strains might be more harmful than those with higher CBD doses. Indeed the numbers of young people seeking drug treatment for cannabis dependence has increased dramatically in the past decade. These findings highlight the need for harm reduction strategies with the aim of educating users to select their cannabis more carefully. However this may be easier said than done, since most users will not have access to anything other than skunk.
After a coffee break we heard from Arno Hazekamp of Leiden University in the Netherlands, and the head of R&D at the Dutch cannabis producer Bedrocan. Arno discussed the therapeutic potential of cannabis, which has been implicated in the treatment of symptoms of many medical conditions including chronic pain, MS, Tourette's and glaucoma. At Bedrocan they are now able to grow cannabis to specific specifications, systematically varying the levels of various cannabinoids. This will allow researchers to run studies and clinical trials with a quality controlled, and most importantly replicable and standardised substances. They are currently setting up a large multi-centre clinical trial to explore the efficacy of their medical cannabis in the treatment of chronic pain, which will be a great step forward in exploring the therapeutic potential of cannabinoids.
Lastly we heard Paul Morrison of Kings College London discuss his own work into the potentially protective effects of CBD against the harmful properties of THC. In a series of acute synthetic cannabinoid administration studies he has demonstrated that those participants receiving a dose of CBD prior to administration of THC did better on delayed recall tasks of episodic memory, and showed reduced THC-elicited paranoia. He highlighted the potential of other cannabinoids also, finding similar protective effects of THCV when administered prior to THC administration.
This was a very interesting session, particularly because we heard from researchers from very different areas of expertise, from Roger's preclinical work right through to Arno's work in industry. The sessions complemented each other well and links could be made between all talks. There is so much promise for the therapeutic value of cannabinoids, and we are only just getting started!
The second poster session of BAP was held on Tuesday afternoon. The topics this time were Cognition (Humans), Drug dependence (Animals), Affective Disorders, Schizophrenia/Psychosis (Animals), Anxiety (Patients), and ADHD/ASD.
Here's a brief selection of posters I found interesting...
Kimberley Mercuri of the Australian Catholic University in Melbourne presented work on episodic future thinking in opiate users. She found that long-term opiate users struggle to achieve mental time travel into the future and to make plans, but did not show the same deficit for recalling events from the past. This is an exciting finding, and may help explain why chronic opiate users have impaired decision making skills, focusing more on present goals rather than more beneficial long-term goals.
Paul Stokes of Imperial College London presented work using PET to assess the relationship between trait impulsivity and human limbic GABA-A receptor availability. He demonstrated that trait impulsivity measured on the Eysenck Impulsivity Venturesomeness and Empathy Questionnaire was positively correlated with GABA-A receptor availability in the right nucleus accumbens, left putamen, and bilateral substantia nigra, but not in the caudate or the globus pallidus. Interestingly, however, no associations were found between limbic GABA-A receptor availability and impulsivity as measured by the Barratt Impulsiveness Scale. This differential finding likely reflects the complexity of the multifactorial facet of impulsivity, and perhaps looking at the various domains that come under the umbrella concept of ‘impulsivity’ will prove fruitful.
In the Affective Disorders marquee there were a number of posters looking at cortisol levels and HPA axis functioning in pregnancy and early-life, and the relationship with anxiety and depression in both mothers and babies. Elizabeth Braithwaite of Oxford University presented some interesting results demonstrating that while all pregnant mothers shown a video of a distressed infant showed an increase in state anxiety, only those mothers who were depressed showed a marked increase in salivary cortisol levels. This finding highlights a potential mechanism by which maternal mood disturbance may impact on fetal development, and suggest that this may play a role in the future emotional development of children.
This was another exciting poster session, with plenty of new research findings across a wide range of topics. Throughout both poster sessions I've been particularly struck by the diversity of research interests that bring people to BAP, and I believe this is one of the key reasons why this conference is always such an exciting and informative experience.
Meg Fluharty, a University of Bristol RA and blogger for the Mental Elf, attended the symposium on ADHD and obesity this morning, and the plenary health session "Is psychiatric diagnosis relevant to psychopharmacological treatment?" Here are her thoughts:
I chose an interesting morning symposium to attend, "ADHD and obesity: Overlapping neurobiology and development of pharmacological treatment," chaired by Ulrich Muller. This session contained a nice balance of both preclinical and clinical presentations (along with male and female, young and old presenters, joked Muller). Emma Robinson started off the first session detailing preclinical models of impulsivity, using animal models. Specifically the FCSRTT (forced choice serial reaction time task), which is used to measure impulsivity, specifically motor control, through premature responses. Robinson displayed how high impulse rats that were free fed (as opposed to food restricted) had a dramatic reduction of response rate on the FCSRTT. The high impulse traits predicted ‘food addiction-like behaviours’ e.g. binge eating, and working harder for the food. This research suggests animal models of impulsivity may provide a valuable method to investigate the relationship of ADHD and obesity, and potentially identify targets of treatment.
Next Sam Chamberlain discussed the pharmacology of impulsivity in ADHD and Impulse Control Disorders (ICD), and emphasised a symptom approach alongside a construct approach of investigating brain abnormalities when identifying these disorders. Chamberlain discussed the high rates of obesity in ADHD, gambling disorder, and other Impulse Control Disorders (ICDS) e.g. hair pulling and skin picking. He highlighted how ADHD, obesity, and IDCs share a lots of phenomenology, comorbidity, and treatments, and how hierarchical approaches indicate overlapping neurobiology and might be able to inform our understanding of treatment mechanisms. Chamberlain concluded by suggesting that aetiological factors and neurological mechanisms require further investigation.
Samuele Cortese highlighted the growing interest of ADHD, obesity, and eating disorders by displaying the increasing publication rates in recent years. He discussed some preliminary results from a systematic review he is conducing on the prevalence of obesity in ADHD: (study protocol here: Cortese et al., BMJ Open 2014 ). Cortese detailed how the number of inattentive and impulsive symptoms was correlated with obesity, while hyperactive symptoms were inversely correlated. Cortese cited a number of longitudinal studies suggesting childhood ADHD was related to later life high BMI and obesity. It’s suggested that ADHD leads to overeating via impulsivity. However alternative studies indicate that ADHD is correlated with Binge Eating Disorder (BED).
Janet Treasure finished with a talk on the pharmacological treatment of eating disorders. She began by discussing the impact of starvation on the brain including reduced plasticity and global thinking, impaired social cognition, and chronic stress and depression. Treasure emphasised that it was not only the amount being eaten, but also the eating behvaiours that could impact the brain (fasting and feasting). She cited that animal models of overeating are more susceptible to addiction to other substances, and changes in amphetamines, opiates, and DA receptors. Treasure discussed the prevalence of both compulsions and impulsions in ED, although depend on diagnosis and stage of illness. Treasure concluded by stating that we need to tailor new treatments for individuals based on diagnosis and the stage of illness.
The Plenary Health Session started off with Shitij Kapur who spoke about stratified psychiatry and psychopharmacological treatment. Kapur discussed how our understanding of the nature and mechanisms of psychiatry has greatly increased in the past decade. However we have still failed to develop tests using biomarkers for various disorders. Kapur cited that difficulties can include diagnosis stability over time, as over half of individuals will change diagnosis over 10 years, and using different diagnostic tools. For example applying the ICD and DSM to the same population will equate an overlap of only roughly 38% in any specific mental illness. Kapur spoke about a systematic review of biomarkers for psychosis he and colleagues conduced, and shared his lessons learned: there were large publication biases found, it was full of ‘’approximate replications’’ where replications didn’t actually use the same methodologies across studies. Finally Kapur stressed that we should not be relying on p-values for clinical reliability.
Next, William Horner discussed the history of categorizing psychotic disorders: from initially just schizophrenia and affective disorders, to the integration of schizoaffective disorder. He discussed a refractory psychosis sample that contained 67% schizophrenia and 33% schizoaffective disorder patients. Schizoaffective disorder was associated with being free of symptoms sometime in the year before being admitted. Horner mentioned that mood disorders may be present in as many as a third of patients with refractory psychosis. Mood disorders, as well as prominent or ‘first rank’ symptoms of schizophrenia may contribute to the treatment response, and the interaction of mood disorders and psychotic symptoms may merit consideration for studies of the mechanism of refractory psychosis and treatment response.
David Nutt gave an interesting talk on the classification of pharmacological treatments and the problems with current drug nomenclature. For example, the use of acronyms might fail to optimise pharmacological knowledge and may result in poor prescribing and research. Nutt cited several alternatives to the current classification system, including one that has been published by ENCP members (Zohar et al, 2014). This system would characterise drugs on a multi axial system. 1: Class & mechanism of action, 2: approved indication, 3: efficacy, side effects & committee notes, 4: neurobiological descriptions both preclinical and clinical. This will be developed into an App and a Book; the alpha version of the app, and initial versions of the book will be available at ECNP in Berlin.
Guy Goodwin gave the final talk on neurocognitive mechanisms and the quest for novel treatments to psychiatric phenotypes. He first spoke on emotional bias in individuals with depression and reduced ability to recall positive words. This recall bias was corrected by a single dose of reboxetine. Next he discussed ‘’cold cognition’’ or difficulties with executive functions in depression, citing a 2% decline of delayed recall abilities for each new depressive episode. Goodwin discussed an fMRI study in which vortoxetine changed the neural activity during N-back performance by reducing dorso-lateral prefrontal cortex and hippocampal activity. Finally, Goodwin discussed reward sensitivity in bipolar disorder. Bipolar individuals reported a 50% reduction in feeling ‘high’ after alcohol intake alongside increase reward sensitivity, compared to healthy controls.
Claire Mokrysz, a Mental Elf blogger who’s studying for her PhD at UCL, has summarized her thoughts on Monday’s poster session, and David Nutt’s fascinating guest lecture “40 years of BAP – a lifetime of psychopharmacology”.
The first of two poster sessions at this year’s BAP was held right before lunch on Monday. The topics included Cognition (Animals), Drug Dependence (Human), Affective Disorders, Schizophrenia/ Psychosis (Human), Anxiety (Non-clinical), Neurodegeneration, Sleep/ Pain, and Eating Disorders. Over 125 posters were presented during the session.
Sadly I could only cover a few of the posters here, so here are just a few of the ones that stood out for me.
Michael Bloomfield at IoP had two posters using [18F]-DOPA PET scanning to study dopamine function in cigarette smokers and cannabis users. He reported an inverse association between striatal dopamine synthesis capacity and self-rated apathy in cannabis users. This finding may explain reduced reward sensitivity and a motivation that we often see in chronic cannabis users.
Annie Campbell at Cardiff presented results of an EEG/MEG scanning study looking at the acute effects of alcohol on resting state networks. She found acute alcohol intoxication altered activity in five functionally relevant resting state networks, increasing activity in the fronto-parietal network while decreasing activity in visual, parietal, motor and parieto-temporal networks. Further work into individual differences in these responses to alcohol could potentially in the future lead to development of bio-markers of risk of alcoholism.
Maxine Howard at UCL presented some findings from two experiments assessing the effects of a 20 hour fasting challenge on impulsive behaviour, designed to mimic the fasting periods patients with bulimia nervosa often undertake. She found participants made more errors of action inhibition on an affective shifting task, and demonstrated higher reflective impulsivity when they were fasted compared to repeated testing on an 'eat as normal' day. However her second experiment failed to replicate these findings, questioning the effectiveness of the fasting paradigm. Nevertheless these findings have interesting implications for the characterisation of eating disorders as disorders of impulsivity.
Affective Disorders had a number of interesting posters presenting research into emotional processing in depressed patients. Beata Godlewska at Oxford presented some exciting results demonstrating that change in neural response to emotional stimuli after 7 days treatment with the SSRI escitalopram predicted treatment response at the end of a 6 week drug course of the drug. This supports the idea that early correction of negative emotional processing biases may be an important mechanism of antidepressant action. This may also provide an early neural biomarker of expected response to antidepressant treatment, which could in the future allow clinicians to identify whether the drugs are not working for an individual without the need for a long period of ineffective treatment. The role of emotional biases and the potential for their use as bio-markers is of course an major theme in psychiatric research at the moment, and hopefully these findings will lead to improved clinical treatment over the coming years.
Well I've only covered a tiny section here, but hopefully it gives a flavour of a great session which promoted plenty of exciting discussions amongst the BAP delegates.
Professor David Nutt, Editor-in-Chief of BAP Journal of Psychopharmacology and a former President of the BAP, gave the guest lecture this afternoon in a talk entitled "40 years of BAP: a lifetime of psychopharmacology".
David took us on a journey starting back in 1974 when he was starting his first elective as a medical student, and which he deemed "the year the receptor revolution began". This year saw the discovery that different antipsychotic dose recommendations were strongly related to the affinity of each drug to dopaminergic receptors- that is to say lower affinity drugs were typically being prescribed at higher doses. Since then, research into dopamine has progressed massively, particularly as a result of PET scanning, and this has in turn allowed us to alter and improve clinical practice.
We then heard about the "evolution, not revolution" of antidepressants over the past decades. While we have seen only marginal gains in efficacy over time, there have been huge improvements in the safety of the drugs we use to treat depression. Again PET scanning of receptors, as well tryptophan depletion studies, have demonstrated the role of serotonin in depression and relapse.
We heard similar stories of the role of the receptor revolution in the development of drugs for treatment of addiction. The development of partial agonist medications such as varenicline for cigarette smoking and buprenorphine for opioid drug dependence, have shown success in helping patients reduce their drug use.
However David then talked of failed receptor targeted treatments, of which there have sadly been many. Many drugs do not translate from preclinical work, and the main issue is that we often don't know why this is. In fact a lot of the progress that occurred in psychiatric drug treatment has been serendipitous- drugs being used to treat other conditions are noticed to have certain psychological effects, for example valproate as a treatment for bipolar disorder originated as a treatment for epilepsy.
So what are the current challenges we face as psychopharmacologists working to advance psychiatric drug development? Firstly the pharmaceutical companies are just not investing in psychiatry any more, likely related to low translation and successes. Secondly David talked about the "anti-biology" stance he believes some psychiatrists and psychologists are taking; criticising the efficacy and overstating the harms of psychiatric drugs. He refers to Peter Gotzsche who in April this year was widely reported in the press stating he believes antidepressants do more harm than good. Applause then followed from the audience when David concluded that in the face of these negative attitudes we must all defend our work and actively stand up for what we do.
So what can we do to address these challenges? We need greater public investment in neuroscience R&D. We need to move fMRI research beyond localisation of activity, and get to the bottom of what activations really mean at the neurotransmitter level. We need better, novel methods to image neurotransmitters in humans. We may need to rethink our statistical models, perhaps another way of describing the data will yield better results. And we need to keep supporting the Journal of Psychopharmacology, which has been at the forefront of psychopharmacology research for the past 27 years.
David finished by thanking Lynne, Susan and Sarah for all their work for BAP and organising the conference, and remembering some great members of BAP who are sadly no longer with us. Philip Bradley, Lyn Pilowsky, Robert Kerwin, Ian Reid, Sean Spence, and Colin Ingram.
A great talk chronicling the advances that have been made over the past 40 years, while highlighting the challenges for the future. Bring on the next 40 years of BAP!