Title: Translational cognitive neuroscience of mood disorders: implications for novel treatments and stratification
Speaker: Roland Zahn (Professor of Mood Disorders & Cognitive Neuroscience / Consultant Psychiatrist, National Service for Affective Disorders, Maudsley Hospital Joint Director, Centre for Affective Disorders, IoPPN, King’s College London)
Location: In Person & Online via Zoom
Abstract: Mood disorders and disturbances occur in patients with frontotemporal and subcortical lesions but are more common in people without brain lesions. Here, we draw on our work in both patient groups and a model of fronto-temporo-subcortical network integration of socio-emotional information via temporal binding (Moll et al., 2005, Zahn et al., 2020) to allow for adaptive mood states. We discuss the early descriptions of Kraepelin’s mixed affective states and suggest a model of four mood states (depressed, anxious, irritable, and elated) and their dynamic evolution and mixing. Blame and praise internalisation and externalisation biases are proposed as key mechanisms underpinning mood states, together with approach/withdrawal-related action tendencies. Whilst self-worth and interest emerge as the most distinctive symptom dimensions, that are necessary for bipolar and recurrent unipolar depressive disorders, we also discuss anxiety as a potential primary symptom in a subgroup of chronic depression. We further provide evidence that patients with depressive mood states, when not accompanied by irritability, exhibited a distinct bias towards social conceptual overgeneralisation towards themselves versus others, whereas combinations of irritability and depression were associated with a non-selective social conceptual overgeneralisation.
Based on a neuroanatomical model of the conceptual self, anterior temporal and subgenual frontal networks and their importance for self-blame and worthlessness, as well as the hypothesised role of septo-hypothalamic networks for affiliative interest are discussed (Moll et al., 2012, Bortolini et al., 2021). The latter were distinguished from ventral striatal networks as relevant for more general approach-related action tendencies and hedonic interest (anticipatory anhedonia), which dissociates clinically from loss of hedonic and affiliative feelings, predicted in our recent work by higher pain tolerance as a proxy for an increased endogenous mu-opioid tone.
Our recent systematic review showed no consistent associations of endogenous opioid function variations with attachment styles, probably due to a lack of studies, but confirmed the association of low human oxytocin function with insecure attachment styles. Yet intriguingly, when seeking to replicate this finding in a well characterised cohort of medication-free patients with remitted major depressive disorder (MDD), we found that low oxytocin levels were associated with non-violent childhood trauma rather than insecure attachment per se, which we conclude may have driven previous apparent associations with insecure attachment.
Lastly, implications for novel neurocognitive, pharmacological, and neuromodulation treatments as well as their stratification are discussed.
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