Neurobiological and Neurochemical mechanisms underlying emotional regulation

Emotions are highly adaptive and complex states, which include our internal feelings, e.g. happiness or fear, our physiological reactions, e.g. sweaty palms, racing heart, and our behavioural responses e.g. approaching something nice and avoiding something harmful. They are triggered by stimuli in the environment, that through past experience, have gained emotional significance. However, our immediate reactions to such emotive stimuli are not always beneficial, and we need to be able to adapt and rapidly modify our emotional responses on a moment-by-moment basis, whether it?s in the workplace, or at home. The ability to regulate our emotions is essential for our physiological, psychological and social well-being and when this ability is impaired it can have a profound, deleterious impact on us. This is illustrated by the range of neuropsychiatric disorders in which emotional disturbance is a core feature, including anxiety, depression, schizophrenia, autism and sociopathy. Anxiety disorders alone have a lifetime prevalence of 16%. It has been shown that in many of these neuropsychiatric disorders there is pathology in various regions of the brain, including the orbitofrontal cortex and amygdala. In addition, there are also imbalances in a number of chemical messengers in the brain, including serotonin. Indeed, many drugs used to treat these neuropsychiatric disorders, target serotonin. However, exactly how these brain regions contribute to emotional regulation, and the role played by serotonin, is poorly understood. We will investigate this by modelling their effects in the brains of experimental animals performing behavioural tests that measure their ability to regulate their emotions. The benefits provided by this Programme lie eventually in understanding how these different regions of the brain control our emotions and how serotonin modulates these brain regions. This information is critical for our ability to develop novel therapies, as well as target current therapies more effectively, for a range of neuropsychiatric

Emotions are highly adaptive and complex states, simultaneously engaging psychological, physiological and behavioral responses that are triggered by the appraisal of external events. However, our immediate reactions to emotive stimuli are not always beneficial, and therefore, an important element of emotion is the ability to appropriately adapt and rapidly modify emotional responses on a moment-by-moment basis. That such regulation is essential for the physiological, psychological and social health of the individual is clearly illustrated by the range of neuropsychiatric disorders in which emotional dysregulation is a core feature, including anxiety, depression, schizophrenia, autism and sociopathy. In all of these disorders there is neuropathology or neurochemical imbalances in neural circuitry that includes the amygdala and orbitofrontal cortex (OFC). Defining the underlying mechanisms by which this orbitofrontal-amygdala circuit contributes to distinct aspects of affective processing will help us to understand the underlying behavioural and social deficits in these disorders. It will also help us to develop new treatments and target current treatments more effectively.
This Programme will investigate the neural and neurochemical substrates of emotional regulation focussing on the OFC and the amygdala and their modulation by the neurotransmitter, serotonin. Major components of emotions are the physiological responses that accompany behaviour including autonomic, neuroendocrine and somatic. These changes in the internal state of the body anticipate, facilitate and accommodate the consequences of our actions. Thus, key cardiovascular variables, namely heart rate and blood pressure will be monitored alongside behaviour. We hypothesise that distinct elements of the orbitofrontal-amygdala circuit are involved in regulating our emotional reactions to cues in the environment that predict appetitive and aversive stimuli, as well as in regulating our instrumental actions, guided by those cues, to obtain or avoid such stimuli. We will assess the role of distinct sub-regions of the OFC in these different aspects of regulation and determine whether such processing is independent, or not, of affective valence. We will also identify the key role played by serotonin, both at the level of the OFC and at the level of the amygdala, in modulating these different aspects of regulation in both the appetitive and the aversive domain. Particular attention will be paid to how dysfunction within the orbitofrontal-amygdala circuit contributes to anxiety and whether changes in serotonergic modulation of this circuit underlie individual differences in anxiety.