Over the course of their lifetime, 10–20% of the population will suffer from major depressive disorder (MDD) (1, 2). Risk of recurrence is high, with up to 35% of patients experiencing at least one further episode within 15 years (3). For up to 25% of patients, MDD takes a chronic course (4). While the core symptoms of MDD concern depressed mood, loss of energy, and negative thought patterns, researchers and practitioners increasingly turned to the concept of mentalising (i.e., the ability to infer thoughts and emotions of other people) to better understand some of the symptoms and to try to predict the course of the disorder. In this review, we will take a social neuroscience perspective to shed light on the role of (reduced) mentalising in depression. Section 2 gives a working definition of mentalising and briefly covers measurements and neural foundations of mentalising in healthy people. In Section 3, we discuss behavioral and neuroscientific findings regarding mentalising in depression, origins of impaired mentalising, and its predictive qualities. Finally, Section 4 covers different treatment options (psychotherapy, pharmacotherapy, and brain stimulation) and their behavioral and neural impact on mentalising. The discussion aims to identify relevant paths for future research.

Broadly speaking, mentalising, also called “perspective-taking,” can be defined as having a mental representation of another person’s mental states (e.g., thoughts and emotions). The word “mentalising” has been in use for well over a century (5), and is currently in use in areas as diverse as evolutionary biology, primate research, neuroscience, psychotherapy, or developmental psychology. Naturally, a concept that is prominent in such diverse areas will have multiple, sometimes diverging definitions. For example, some authors use mentalisation only to refer to the representation of affective states and “theory of mind” (ToM) to describe the representation of epistemic states (like beliefs or intentions) (6, 7). For others, ToM comprises both (8), sometimes with a differentiation between affective and cognitive ToM (9, 10). In this paper we follow the broader and common meaning, defining mentalising as the ability to recognize and form a mental representation of both affective and cognitive states of others while suppressing one’s own (11). Mentalising is crucial for basic processes like emotion recognition (12) as well as for successful social interactions and develops gradually during childhood (13). While a comprehensive review of mentalising in healthy people is beyond the scope of this article [but see (14)], we will here present key findings relevant for the understanding of (neural) alterations related to mentalising in MDD.

Traditionally, research on MDD has focused on the core emotional and cognitive symptoms such as low mood, loss of interest, loss of energy, reduced concentration, negative thought patterns or rumination. However, interpersonal relations and mentalising have also garnered substantial interest (28). Indeed, a recent meta-analysis established substantially reduced mentalising in MDD, for both cognitive and affective mentalising, and for both decoding tasks (e.g., emotion recognition) and reasoning tasks (e.g., identifying false-beliefs or intentions) (29, 30). For the affective component, these deficits might partly stem from a negative evaluation bias in MDD, so that patients with MDD are more likely to infer negative mental states (31, 32). Neither age nor gender seem to influence the degree of impairment, while people with more severe depressive symptomology show the largest deficits in mentalising (29, 30). Because studies showing the most pronounced deficits typically included patients with a chronic course of MDD, some authors have argued that mentalising deficits are particularly prominent in chronic depression (33). However, when directly comparing first-episode and chronic MDD, these differences apparently do not appear (34, 35). While chronicity therefore cannot be regarded as moderator of mentalising deficits, there is evidence that mentalising might be more strongly impaired in MDD with psychotic symptoms (36). Additionally, one might wonder whether specific subtypes of patients with MDD also show specific impairments (e.g., only relating to affective or cognitive mentalising). This sounds particularly prominent as MDD is somewhat of an umbrella category, and the pathogenesis and biographical details differ vastly. However, concrete evidence for specific subtypes regarding mentalising is sparse and overall, both affective and cognitive mentalising seemed to be impaired in MDD. As of yet, the only reliable finding regarding subtypes seems to be that mentalising deficits correlate with severity of symptoms, with more severely depressed patients showing the most pronounced deficits in mentalising, and sub-clinical samples showing no mentalising deficits at all (29). These findings, however, extend to mentalising overall, and there is no evidence for a specific pattern of mentalising deficits.

One might also speculate about the influence of comorbid disorders on mentalising: for example, disorders like social phobia or eating disorders seem to correspond to over-mentalising (37, 38), yet at the same time often occur together with MDD. As, however, over- and under-mentalising can co-occur in the same individual (39), these findings might be less puzzling than one might think (38). Still, it remains entirely possible that different subgroups exhibit specific patterns (e.g., patients who suffered from depressive symptoms since adolescence vs. patients who developed them only later in life). Until more research is conducted, however, any findings on depression subtypes should be interpreted as preliminary results, and we do agree with Bora’s and Berk’s opinion (30) that more research into mentalising in different subtypes of MDD is needed.

Given the high number of patients with MDD with comorbid personality disorders, one might wonder whether it is the personality disorders, not MDD, that actually leads to decreased mentalising. This might sound even more plausible because by its very definition, personality disorders are characterized by impaired self-functioning or interpersonal functioning (40). However, a number of studies showed that deficits in mentalising also occur in MDD when controlling for personality disorders (41, 42) or when excluding patients with personality disorder altogether (43, 44). Thus, is seems valid to assume that reduced mentalising in MDD is not just confounded by comorbid personality disorders.

As most studies on mentalising in MDD are cross-sectional, they cannot inform us on whether reduced mentalising is a result of MDD, or whether it precedes the disorder and thus constitutes a risk factor or even cause of MDD. There have been, however, some theoretical attempts to explain a potential causal effect of mentalising on MDD. For example, in the context of CBASP, it is assumed that (chronically) depressed patients exhibit (child-like) preoperational thinking patterns, struggle with “true empathy,” and are “pervasively egocentric.” This is supposed to lead to frustrating interpersonal situations that do not satisfy one’s interpersonal needs, which ultimately would lead to the development and maintenance of depressive symptoms (45). Another explanation is the idea that reduced theory of mind leads to a pattern of social interaction that might drive other people away, with the resulting social isolation promoting depressive symptoms (46). Additionally, there is evidence that deficits in ToM persist after remission: Inoue et al. (47) showed that patients with remitted MDD performed worse than matched controls in a false-belief task (but no differences were observed in factual observations during the task). These results are supported by Ladegaard et al. (48), who showed impaired social cognition (including ToM) but normal cognitive functioning. Additionally, stronger deficits in ToM predict both a higher risk of relapse and more severe symptoms in MDD (49, 50). Thus, it seems likely that reduced mentalising contributes to MDD, and is not merely a consequence. It should be noted, however, that the opposite route of action has also been discussed. For example, it has been proposed that a negativity bias and constant rumination in MDD lead to impaired mentalising because less cognitive resources are available to accurately interpret social cues, or that social withdrawal typical to MDD leads to less “practice” of mentalising and social skills (29, 51).

There are only few neuroscientific studies investigating mentalising in patients with MDD. Lai et al. (52) showed altered functional connectivity in a network comprising areas that have been related to ToM before, such as the left precentral gyrus, left angular gyrus, bilateral rolandic operculum and left inferior frontal gyrus. However, as these brain areas are involved in many cognitive processes, it remains speculative whether alterations are actually related to altered ToM. Converging evidence stems from studies on postpartum depression: using near-infrared spectroscopy, Morgan et al. could analyse brain connectivity during a naturalistic mother–child interaction (reading a book together) (53). Mothers with more severe depressive symptoms showed a lower connectivity between the right TPJ and lateral PFC, but greater connectivity between the right TPJ and the anterior medial PFC. The authors interpret their results as indication that during mentalising about their infant’s thoughts and feelings, mothers with MDD might be less able to express and regulate their own emotions, but better at engaging in emotional bonding with their infants, although this remains somewhat speculative.

At least partly, deficits in mentalising and corresponding neural alterations seem to be rooted in negative experience early in life. Indeed, childhood maltreatment is not only a risk factor for (chronic) depression (54), it also predicts lower mentalising later in life (55, 56). Additionally, Hentze et al. (55) showed that childhood maltreatment correlates positively with amygdala activation during an affective ToM task. This is in line with research showing that childhood maltreatment leads to heightened amygdala responsiveness as well as reduced gray matter in insula, orbitofrontal cortex, anterior cingulate gyrus, superior temporal sulcus, middle temporal lobe, and caudate (57).

The fact that childhood maltreatment predicts both mentalising and MDD gives further support to the idea that mentalising might precede MDD and that reduced mentalising might pose a vulnerability for MDD, potentially mediated through neural changes in the amygdala system. While the amygdala might not be a prototypical part of the mentalising system, it has been argued that the amygdala is involved in fast, automatic mentalising (58) and patients with amygdala damage show impairments in mentalising (59). This might be particularly true if the mentalising task at hand involves emotion recognition and processing, whereby the mentalising system might require output from the amygdala (60).

Interestingly, neural alterations are also visible in individuals with high familiar risk for MDD. Using a family network analysis, Abraham et al. (61) showed that individuals with heightened familiar risk exhibited reduced influence of the inferior frontal gyrus and posterior superior temporal gyrus within a social cognition network. Additionally, these neural alterations predicted both depressive symptoms and deficits in interpersonal adjustment at an 8-year follow-up.

Taken together, there seems to be clear evidence that mentalising is reduced in MDD and that patients with reduced mentalising are at higher risk of recurrence, that mentalising deficits correspond to pronounced changes in the “social brain” and that these cognitive and neural alterations can at least partly be matched unto early-life stressors.

Mentalising capacity is substantially impaired for many patients with MDD. These deficits seem to stem at least partly from negative early-life experiences (e.g., childhood maltreatment) and correspond to neural alterations to the mentalising network (e.g., TPJ, inferior frontal gyrus) and connected structures (e.g., amygdala). MDD is currently treated with a number of different approaches, yet evidence of effects on mentalising are rare. However, a number of psychotherapeutic approaches have started to focus implicitly or explicitly on mentalising to improve patients’ well-being. In light of the evidence today, we believe that mentalising might be a prominent target to improve the course of MDD and prevent recurrence of the disorder. However, several aspects remain unclear and should be investigated in future research. In particular, it might be worth identifying whether a causal link between reduced mentalising (before onset of the disorder) and MDD does exist, although this would require large longitudinal data sets. Whether strengthening mentalising can reduce risk of relapse or even improve well-being of patients in acute phases would be another valuable line of research. Comparisons of different types of mentalising, and comparisons of different groups of patients (e.g., first episode MDD vs. chronic depression) are still rare and might be worthwhile investigating. Similarly, one might wonder whether patients that developed depressive symptoms as reactions to acute life-stressors but did not suffer from negative events during childhood are similarly affected in terms of mentalising capacity. It might also be helpful to conduct more longitudinal research, to better understand when reduced mentalising (or social cognition more broadly) is a cause for MDD, and when it can also be a consequence of it. Finally, much of the existing knowledge stems from research from countries of the Global North, even though culture influences the role of social cognition in mental disorders (104). Getting a better understanding of the role of reduced mentalising for different patient populations might help to tailor more targeted interventions. Because mentalising deficits sometimes persist after the end of an acute depressive episode (47), but also predict future recurrence of MDD, investigating mentalising training as relapse prevention after successful therapy would be very informative. Because much is still unknown about the role of mentalising in MDD, researchers might want to include at least a basic mentalising measure in future intervention studies. From a neuroscientific point of view, it could be interesting to not only measure neural alterations in patients with MDD, but also changes following targeted interventions. Ultimately, of course, patients with MDD seek help not because they want to improve their mentalising abilities, but because they suffer from the core depressive symptoms. Thus, improving mentalising will likely not be a target in and of itself, but rather a tool to achieve better quality of life. While the existing evidence warrants caution, taking a stronger focus on (improving) the mentalising capacity of depressed patients might still be a promising lever for change.

BPL and DK developed the concept of the manuscript. BPL wrote the first draft. DK and KK read and complemented the manuscript. All authors contributed to the article and approved the submitted version.

This work has partially been funded by the Typhaine Foundation.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.