Understanding of Self and Others: Neurobiological Underpinnings of Social Cognition

This chapter examines the processes underlying interpersonal interactions in both healthy control individuals (HC) and those with major depressive disorder (MDD). The chapter focuses on four key types of social cognition that give rise to the intricate and dynamic nature of human social functioning, including self-referential processing, other-processing (‘theory of mind’), moral emotion, and social decision-making. It reviews studies investigating the neural substrates of social cognition in HC and MDD, most commonly using functional magnetic resonance imaging. Key brain areas identified include prefrontal cortex (PFC; including, most prevalently, the orbitolateral, medial–lateral, and dorsolateral PFC), temporal–parietal regions (in relation to theory of mind), and subgenual anterior cingulate cortex (in relation to both specific moral emotions, such as guilt, and moral content more generally).

Neurocircuitries of Emotion Processing Affected in Major Depressive Disorder

Impairments in processing emotions are a hallmark feature of depression. Advances in neuroimaging techniques have rapidly improved our understanding of the pathophysiology underlying major depression. In this chapter, we provide an overview of influential neural models of emotion perception and regulation and discuss the neurocircuitries of emotion processing that are affected. Major depression is characterized by impairments in widespread brain regions that are evident in the first episode. Models have sought to distinguish the neural circuitry associated with recognition of the emotion, integration of somatic responses, and monitoring of the affective state. In particular, there has been a preponderance of research on the neurocircuitries affected during processing of mood-congruent negative emotional stimuli in depression. While neuroimaging correlates have been investigated and models proposed, these findings have had limited clinical applicability to date. Novel methods such as multivariate pattern recognition applied to neuroimaging data might enable identification of reliable, valid, and robust biomarkers with high predictive accuracy that can be applied to an individual. Last, we discuss avenues for extension and future work.

Cognitive Dysfunction as a Symptom Dimension Across Major Psychiatric Disorders

Cognitive dysfunction is a symptom domain across multiple psychiatric disorders. Cognitive deficits in individuals with major depressive disorder (MDD) and bipolar disorder (BD) are significant contributors to global occupational and functional disability. The subdomains of learning and memory, executive function, processing speed, and attention and concentration are significantly impaired in individuals with MDD and BD. Treatment outcomes of cognitive symptoms with first-line agents have been suboptimal. Neuroinflammatory pathways are hypothesized to play key roles in the pathoaetiology of cognitive symptoms in MDD and BD. There is compelling evidence to suggest that elevation of systemic proinflammatory cytokines is involved in neurotoxicity, apoptosis, and aberrant neurocircuit function. These substrates offer opportunities to identify relevant biomarkers, refine treatment targets, and manage cognitive deficits across major psychiatric illnesses. This chapter provides an overview of cognitive symptoms across MDD and BD and discusses potential neurobiological substrates contributing to cognitive dysfunction.

Major Depressive Disorder as a Disorder of Cognition

Depression is one of the leading causes of disability worldwide. People who experience depression face difficulties in many areas of their daily living. Cognitive problems are commonly associated with depression and have significant impact on social and work functioning. The lack of treatments specifically aimed at improving cognition may lead to persistent cognitive dysfunction in depression, and this is a major factor in depression-related disability. In this chapter, we will discuss the case for formulating major depressive disorder as a disorder of cognition and motivation, and the interaction between the two. We will also highlight cognitive dysfunction as a target for treatment in depression.

Can Non-Pharmacological Antidepressant Treatments Influence the Processing of Affective Information?

Depressive disorders are commonly associated with abnormalities in affective cognition. When processing information with emotional content, the depressed brain typically exhibits mood-congruent negative biases; that is, an abnormal preference for negative relative to positive information. In turn, recent psychopharmacological research has revealed that antidepressant drug treatments have the ability to push affective information processing more towards a preferential processing of positive information. These observations have led to the postulation of a cognitive neuropsychological model of antidepressant treatment action. This model suggests that negative biases play an important causal (rather than just epiphenomenal) role in the development of depressed mood and efficacious antidepressant interventions exert their clinical effects by acutely counterbalancing these cognitive abnormalities. In this chapter, we extend the focus to non-pharmacological treatments for depression and ask whether they too can influence affective cognition, and, if so, what these effects look like. We highlight recent studies investigating how cognitive behavioural therapy, electroconvulsive therapy, transcranial direct current stimulation, and environmental therapeutics impact on affective information processing in patients with depression. We show that, for each of these treatments, at least some evidence exists that suggests an influence on affective cognition and that in some cases the observed effects are directly in line with the cognitive neuropsychological model. However, as will become clear, the currently available evidence is rather sparse and, in many regards, incomplete. We therefore conclude that—similar to antidepressant drugs—non-pharmacological treatments can also influence affective information processing in patients with depression. However, whether these changes can counterbalance negative biases, and whether they are causally involved in the clinical effects of the different treatments, remains to be elucidated by future research.

The Assessment of Cognitive Dysfunction in Major Depressive Disorder

Accurately capturing an individual’s cognitive status is a key requirement for identifying levels of impairment in patients with central nervous system indications, including in those with diagnoses of major depressive disorders (MDD). This requirement extends to the determination of whether a therapeutic intervention has impacted cognition and, if so, the extent to which this has occurred. In this chapter we will consider these issues with respect to the assessment of cognition in patients with MDD. We begin with a review of performance on measures reported in recent meta-analyses and with a particular focus on their sensitivity to treatment effects. We proceed to a consideration of how best we might accurately capture levels of cognitive performance and the precautions required to reduce sources of measurement error. These methods will then be considered in the context of a recent case study of a treatment (vortioxetine) development programme. The issues explored in the context of assessing cognition in the vortioxetine programme are then considered in the context of screening for deficits in patients with MDD. We close the chapter with a summary and recommendations for the accurate assessment of cognition, as well as a brief consideration of how technological developments might aid this process.

Clinical and Functional Characteristics of Cognitive Dysfunction in Major Depressive Disorder

Cognitive dysfunction is a cardinal symptom of depression that significantly contributes to the psychosocial and occupational impairment experienced by patients with major depressive disorder (MDD). This chapter examines the important clinical characteristics and functional impairments associated with cognitive dysfunction in patients with MDD. Although cognitive dysfunction can also be identified in first-episode MDD, depressed patients with greater illness burden (severity, recurrence) and specific subtypes (melancholic, psychotic) have more severe cognitive deficits and poorer functioning. Cognitive dysfunction can also persist during treatment of depression, even when other depressive symptoms are in remission, and can be a barrier to functional recovery. Clinicians should therefore assess, monitor, and target cognitive dysfunction in the treatment of patients with MDD to optimize their potential for full functional recovery.

Emotional and Cognitive Consequences of Social Rejection: An Entry Door to Major Depression

Interpersonal factors are strong predictors of the onset and course of major depression. However, the biological and neural bases of interpersonal difficulties in major depression are unknown. In this chapter we describe a general homeostatic system that monitors the social acceptance of individuals. We show that this system is activated in response to actual or putative threats to social acceptance and signals of social rejection. Our model describes a cascade of cognitive, emotional, and behavioural consequences of social exclusion. The model emphasizes the role of specific regions—the subgenual anterior cingulate, the insula, and the default mode network—in the detection and regulation of social signals. Hence we propose that major depressive disorder is tightly linked to the processing of social exclusion and may represent a specific impairment in the homeostatic system that monitors social acceptance.

Clinical Characteristics of Social Cognitive Processes in Major Depressive Disorder

Dysfunctional social cognition describes an important symptom of major depressive disorder (MDD). This dysfunction relates to various aspects of perception of emotional states in oneself and in others, but also applies to complex situations such as social communication. The majority of evidence supports a theory that patients with MDD show a negative bias towards ambiguous emotional information in all domains of social perception. It appears that social cognitive function varies in the course of MDD due to treatment and symptom severity. Therefore, social cognitive dysfunction often presents as a subtle phenomenon vulnerable to further disturbing influences by confounding variables. Analyses often do not consider important confounders such as symptom severity and type of treatment. Social cognitive research uses a broad spectrum of measurements with varying quality of standard psychometric criteria. Future investigations should use standardized measures with large normative samples to avoid distortions of results.

Networks of Cognitive Processes: Functional and Anatomical Correlates of Cognition, Emotions, and Social Cognition

Networks of cognitive processes describe some of the key findings emerging from cognitive network neuroscience. Cognition is organized in distinct networks in the human brain. These cognitive networks interact via complex dynamics to process our environments and enact our decisions on the world. Within the emerging subdiscipline known as cognitive network neuroscience, we can connect classical neuroscience approaches to network science. This allows us to consider how major cognitive functions ranging from sensation to cognitive control and emotion are organized in the human brain. Through the lens of network neuroscience, we can enrich our understanding of normal and disordered cognitive function to be manifestations of processes and representations in ordered or disorded neural networks.