BNA2013: Impulsivity compulsivity and habit formation

Report on a session conducted at the ‘Festival of Neuroscience’, organised by the British Neuroscience Association.

The ‘Festival of Neuroscience’ was a 4-day scientific event held at the Barbican centre in London, UK. This was an event organised by the British Neuroscience Association (BNA) in partnership with eighteen societies with interests in both clinical and non-clinical aspects of neuroscience. There were 56 scientific sessions and 7 plenary lectures involving more than 240 speakers, over 80 from outside the UK. The session on ‘Impulsivity Compulsivity and Habit Formation’ was a contribution from the British Association for Psychopharmacology (BAP).

Dr Luke Clark opened the session by introducing the speakers for the first 3 lectures, with Dr Clark himself presenting the last lecture.

Professor Dan Stein from the University of Capetown, South Africa opened the lectures offering an overview on obsessive-compulsive and related disorders. Professor Stein began by defining obsessions and compulsions. He then described the concept of obsessive-compulsive spectrum disorders – a group of disorders sharing a common theme – intrusive thoughts and repetitive, stereotyped and ritualistic behaviours. It was notable from epidemiological studies Professor Stein quoted, that obsessive-compulsive disorder (OCD) stood 4th in the list of mental illnesses and tenth most disabling amongst various disorders. It was also interesting to note how the thinking on OCD has changed from a disorder with psychodynamic underpinnings to one with a neuropsychiatric basis with disordered neurocircuits, as evidenced from psychopharmacological and neurocognitive and neuroimaging studies. He also spoke about the evolving nature of clinical classificatory systems, especially the Diagnostics and Statistical Manual (DSM) to reflect the advances in research on OC spectrum disorders. Thus in DSM-5, OCD and some of the related disorders (from the spectrum) have been brought together under the category of obsessive-compulsive and related disorders.

Professor Stein then lectured on the evidence for shared neuroanatomical, genetic and immunological characteristics of spectrum disorders such as OCD and Tourette’s syndrome. He discussed the utility of SSRIs in the treatment of OCD and evidence for the same from translational research, for instance evidence from animal studies. Acral lick dermatitis in dogs has been noted to respond to SSRIs. However, according to him, the lack of response of skin picking disorder (SPD), trichotillomania (TTM) and hoarding to SSRIs reflect the need to further explore the exact nature of the link between the various spectrum disorders and their underlying neurobiology. This was highlighted further through a discussion about the role of the neurotransmitter, dopamine, in the treatment of spectrum disorders, suggesting that there may be more to the story than just serotonin. Professor Stein then offered a useful ‘ABC’ model to link clinical symptoms with possible underlying neurotransmitter dysregulation. Thus the affective component may be linked to serotonin, the behavioural addiction (related to reward mechanisms) could be linked to dopamine and cognitive dyscontrol related symptoms with possible link to glutamate systems. Professor Stein talked about the emerging evidence for a glutamate modulator, N-acetyl cysteine, in the treatment of OCD. Likewise, dopamine antagonists (antipsychotics ) have fairly strong evidence as augmentation treatments in OCD. Professor Stein concluded his lecture by stating that for a better understanding of obsessive-compulsive spectrum disorders it may be necessary to think of obsessive/compulsive behaviour across multiple dimensions rather than a single spectrum. Moreover, according to him, for a better understanding there is a need to increase detection rates and improve accuracy of diagnosis of these disorders, especially considering that they often end up being assessed and treated in non-psychiatric settings such as dermatology, plastic surgery or paediatrics to name a few.

This lecture was followed by questions from the audience on potential differences between response to SSRIs in animal models and human clinical studies and role of clomipramine/SSRIs in TTM.

Professor Naomi Fineberg presented the second lecture of this session. She described OCSD as behavioural disorders wherein behaviours are performed according to rigid rules to reduce or avoid unpleasant consequences. In these disorders there seems to be a shift in the long run from impulsive to compulsive behaviour, resulting in ‘habits’. She discussed at length the neurobiological underpinnings of compulsivity, for instance neurocognitive endophenotypes and brain imaging correlates. These are described below.

Response inhibition and cognitive flexibility are two of the cognitive endophenotypes researched extensively. Studies that tested ‘impaired inhibition’ using stop signal reaction task (SSRT) found that patients and unaffected first-degree relatives were impaired significantly more than healthy controls. Similar results were observed on the task measuring cognitive inflexibility using intra-dimensional/extra-dimensional (id/ed ) task. Changes in grey matter volume correlated with the degree of impairment in both patients as well as healthy relatives in the bilateral orbito-frontal cortex, Right inferior frontal gyrus, Right superior frontal and anterior cingulate regions. Diffuse tensor imaging demonstrated reduced white matter density in Parietal lobe regions, whereas there was increased white matter density in the orbito-frontal regions. Impaired cognitive flexibility, according to Professor Fineberg, has also been demonstrated in animal studies using marmosets. id/ed impairments correlated with changes in grey matter volume in the lateral prefrontal cortex. Finally, on fMRI studies, patients and relatives showed significant underactivation during reversal learning.

Professor Fineberg then talked about functional connectivity and how this was tested by referring to a study which compared OCD with stimulant drug dependence (SDI). Functional connections, specifically between superior and orbito-frontal cortex, were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. The conclusion was that these disorders, despite their common ‘compulsivity’ character, are not similar to each other.

Professor Fineberg ended her lecture with a discussion on the hypothesis that compulsions could be the result of habit formation. Patients with OCD tend to fail to inhibit response to devalued outcomes. Alterations in cortico- striatal connectivity may underlie differences in habitual and goal-directed behaviour. A further study was carried out to test whether OCD was an enhanced avoidance habit. In an experiment, patients with OCD continued to press a pedal to avoid a mild shock, even though they were told that the wire that delivers it was disconnected. The conclusion was that avoidance habits can, in due course, become compulsive. Thus impaired behavioural inhibition and habit learning, according to Professor Fineberg, could contribute to compulsivity and the potential brain correlates include orbito-frontal cortex, caudate and putamen.

Questions followed this lecture as well. These were in relation to cross-cultural variation in OCD and a question specifically related to the strength of devaluation in one of the above mentioned experiments testing response of OCD patients to devaluation of rewards.

Dr Sam Chamberlain presented the third talk on trichotillomania (TTM), which he described as a useful model to learn impulsive-compulsive disorders. Grooming, according to him, does exist in the population as habits. Disorder in his words results from a loss of ‘top-down’ control. Dr Chamberlain highlighted historical perspective to TTM. For instance, TTM has been mentioned in the Bible and Homer’s ‘The Iliad’. Hippocrates is noted to have recommended checking patients for hair-pulling as part of every general physical examination. Understanding TTM, according to Dr Chamberlain, is crucial as this illness is associated with long-term sequel. For instance, it could lead to Axis 1 co-morbid disorders, infections, hair loss and psychosocial complications.

Dr Chamberlain then discussed treatment options for TTM. ‘Habit reversal’ has been reported to be more effective than medication in TTM. Amongst medication, Clomipramine has been noted to be superior to placebo. Olanzapine and N-acetyl cystiene were thought to be promising, but results with n-acetyl cystiene have been negative. Talking on genetic studies in TTM, Dr Chamberlain referred to a single twin study which produced 38% concordance. He then lectured on animal models in TTM. One of the models he described was the ‘barbering mice’, resulting from deletion of Hcy B8 gene leading to excessive grooming. Interestingly, these genes have been expressed in the striatum; however, the only cells expressing it were microglia which sub-serves immune functions. Further, when these cells were transplanted from the marrow, this resulted in reversal of grooming.

Dr Chamberlain then discussed neuroimaging findings in TTM. Compared to controls, subjects with TTM showed reduced grey matter volume in amygdala, putamen and hippocampus. Diffuse tensor imaging studies have noted reduced white matter tracts in TTM. Neurocognitive tests as described above by Prof Fineberg in OCD have also been conducted in TTM. Thus, the longer the SSRT values, the more impaired the patients are in TTM. Dr Chamberlain noted that, in keeping with the concept of spectrum disorders, SSRT is impaired in OCD, TTM, skin picking disorder (SPD) and pathological gambling (PG). Further, Atomoxetine was noted to improve SSRT performance in humans and increase brain activation during inhibitory control in the right inferior frontal gyrus, suggesting potential role of noradrenergic agents in TTM. Dr Chamberlain concluded the lecture with the suggestion that TTM could be the result of excessive drive in the habit circuitry and lack of enough top-down control from the inhibitory circuitry.

Questions following the lecture included whether, in TTM, pre-movement tension (as is noted in tic disorders) has been tested. This was followed by questions on the role of ADHD medications and antihistaminics in the treatment of TTM. A further question was about the possible role for opioid modulators in the treatment of TTM, with the person suggesting that there could be a role for studying receptors linked to the nerves around hair follicles in TTM.

Dr Luke Clark presented the final lecture on pathological gambling. He started his discussion by introducing the terms: gambling, responsible gambling, problem gambling and the extreme form of gambling included in DSM-5 – pathological gambling (PG). It was noted that PG has been moved to the category on substance misuse disorders in DSM-5 and is the only behavioural addiction included under that category. Dr Clark further described the interactive triangle between the host, the agent and the environment which ultimately results in the expression of the disorder.

Dr Clark then discussed cognitive tests in PG. Subjects with PG were noted to be more impaired than controls on SSRT. Impairment in decision-making was observed on the ‘Cambridge gambling task’. Subjects with PG chose the wrong colour, suggesting that they bet more frequently, the more uncertain the task was. Likewise, on the ‘delayed discounting task’ they chose a smaller immediate reward rather than a delayed reward of a higher value. According to Dr Clark, on tasks of learning those with PG are impaired on both stages of learning (initial and reversal), suggesting that they are not ‘compulsive’ (unlike those with OCD). He then moved on to neurochemical correlates of PG. He noted that there is a reduced level of dopamine (D2) binding in subjects with PG. Further, dopaminergic agonists tend to increase gambling behaviour. However, assay of dopaminergic transmission has not noted any difference from controls. Dr Clark then lectured on other aspects of neurobiology of PG. In subjects with PG there are higher levels of mood related impulsivity and on this measure they tend to overlap with subjects with alcohol dependence. Studies on gambling behaviour following head injury have suggested a possible role for ventro-medial prefrontal cortex.

Dr Clarke then discussed certain tests that formed the psychological basis for PG. Thus, ‘near misses’ are less pleasant than ‘full misses’ in subjects with PG. fMRI studies have noted that near misses also drive ‘win-sensitive’ areas. Further studies have linked response to ‘near misses’ to insula and the mid-brain. In experiments testing ‘gamblers fallacy’, those with PG, according to Dr Clarke, demonstrated sequential biases in choice of results – in other words they were less likely to choose what was prescribed as a consistent result. Discussing this phenomenon further, he alluded to a study which compared subjects with brain injury to healthy controls. It was noted that the above fallacy was abolished in those with injury to the insula region. The role of insula in ‘decision making’ in PG, according to him, was further demonstrated from studies that showed reduced firing in the area of insula in PG as opposed to those with OCD were the opposite was noted.

The audience responded with questions after this lecture as well. These included queries on gender differences in PG and the influence of media on rates of PG. A question on whether there has been research on why good gamblers do well was thought-provoking. Another question was in relation to animal models in PG.

Overall this was a well-attended session with high-quality lectures. All the speakers presented to a packed audience. That the sessions generated a lot of interest was demonstrated by the fact that the audience had questions after each lecture as well as at the very end for all the speakers. Also, the nature of questions from this very attentive audience suggested a keen interest in the topics that were covered in the four lectures on this fascinating spectrum of obsessive compulsive disorders.

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