Long before it was described in medical nosography, the term “apathy” existed as a philosophical concept whose meaning gradually evolved. The word apathy originates from the Greek ἀπάθεια (apátheia), which can be broken down into the prefix “a” (without) and the root “pathos” (feeling, emotion, illness). Originally, it referred to the absence of feeling or, alternatively, the absence of suffering, something considered a virtue by Stoic philosophers. Indeed, the Royal Spanish Academy (RAE) defines apathy as “impassivity of the mind,” a definition close to the Stoic one, but also as “slackness, indolence, lack of vigor or energy.” On the other hand, the Oxford English Dictionary defines apathy as “lack of interest or enthusiasm,” which captures a cognitive aspect of apathy (lack of interest) but also an emotional dimension (enthusiasm). Finally, the French Larousse Dictionary defines apathy as “the indolence or indifference of someone taken to the point of total insensitivity,” adopting the Stoic perspective but also adding the meaning of “slowness to act or react, passivity, or inertia,” which particularly emphasizes its motivational aspect.

Thus, apathy as a philosophical concept is viewed as the absence of emotions or passions that could disturb the individual’s mind. It is, therefore, an intentional attitude closely linked to will. This concept has partially persisted into modern times, incorporated into some definitions of apathy. However, the positive connotations that Stoic philosophers associated with this state have not been carried over.

The adoption of this concept by science in general, and medical science in particular, did not occur until the 19th century, when numerous experts in medicine and psychology detected, reported, and described these alterations in their patients, giving rise to numerous concepts that today partially or completely overlap with the concept of apathy (Prange et al., 2018).

In parallel with research on patients with neurological diseases, much of the classical descriptions and reflections on apathy and associated alterations were made in the context of mental illnesses, particularly schizophrenia. While in the context of neurocognitive disorders, apathy is the most frequently used term, in the domain of psychiatric and neuropsychiatric disorders, the term “negative symptoms” was historically coined to refer to one of the core components of psychotic disorders, especially schizophrenia (Bleuler, 1950; Kraepelin, 1919). Negative symptoms involved a significant reduction in goal-directed activities, pleasure, emotional expression, and speech (Strauss & Cohen, 2017).

As Marder and Galderisi (2017) note in their review of the origins of the study of negative symptoms in schizophrenia, the first descriptions of these symptoms date back to the early 19th century. In 1809, John Haslam described a mental illness in young people characterized by blunting of sensitivity and emotional indifference (Haslam, 1809), which are now considered core features of the negative symptoms in schizophrenia and other neuropsychiatric disorders. Almost simultaneously, Philippe Pinel described “idiocy” in his treatise on mental illness as “a more or less absolute destruction of the functions involved in understanding” but also in “heart disorders,” highlighting the affective dimension of mental illness (in Dollfus & Lyne, 2017). During the 19th century and the first half of the 20th century, not only were the behaviors of apathetic patients or those with negative symptoms described, but attempts were also made to offer explanations for the possible underlying mechanisms. This is the case of the eminent neurologist John Hughlings Jackson, who regarded negative symptoms as “losses or reductions in aspects of higher cognitive and emotional functions,” while positive symptoms (hallucinations and delusions) were seen as a “phenomenon of release,” that is, distortions or episodic exaggerations of normal functioning (Jackson, 1885).

Building on the idea that negative symptoms reflect impairments in cognitive and emotional functions, Kraepelin (1919) described the negative symptoms of dementia praecox as “a weakening of the emotional activities that are the primary drivers of will, emotional blunting, failure of mental activities, and a loss of control over willpower, effort, and the ability for independent action.” As early as 1906, Kraepelin emphasized the importance of analyzing the affective domain rather than the intellectual one, highlighting that emotional blunting, and negative symptoms in general, were the predominant features of this illness (Dollfus & Lyne, 2017).

Just a few years later, in 1922, psychiatrists Dide and Guiraud (1922) proposed describing dementia precox as “juvenile atimormia.” The neologism atimormia, coined by the authors themselves, was derived from the Greek words thimos (feeling or mood) and horme (impulse), preceded by the privative “a.” Thus, it referred to a lack of feelings and impulses in the absence of physical alterations. This term was later revived to describe the symptoms exhibited by patients with lesions in the striatum (Habib & Poncet, 1988).

Bleuler (1950), in line with previous ideas, considered emotional blunting to be central to schizophrenia, a term he introduced, while defining hallucinations, delusions, and catatonia as acute exacerbations (Bleuler, 1950). One of his descriptions of patients with schizophrenia highlights some of the most striking features of severe apathy: “Many schizophrenics… sitting… with expressionless faces, hunched over, are the very image of indifference. They allow themselves to be dressed and undressed like automatons, led from their usual place of inactivity to the dining room and back again without showing any signs of satisfaction or dissatisfaction.”

Thus, in addition to providing insightful descriptions of behavioral deficits that we now recognize as manifestations of apathy, they proposed several mechanisms that might be associated with this alteration. Specifically, they focused their explanations on the emotional dimension of apathy (flattening, blunting, lack of reactivity) and suggested that, unlike positive symptoms such as delusions or hallucinations, negative symptoms resulted from a structural deficit in higher cognitive and emotional processes. That is, apathy and other defect-related symptoms in psychiatric disorders are always accompanied by cognitive deficits.

Research on negative symptoms in mental illness and apathy in neurological studies has traditionally progressed in parallel, with only recent transdiagnostic formulations of this disorder fostering a closer alignment between these two perspectives (Husain & Roiser, 2018). In this regard, the current conceptualization of apathy stems from studies conducted with neurological patients in the 19th and 20th centuries. Prange et al. (2018) outlined a conceptual journey of the term ‘apathy’ and other related terms, based on the study of neurological patients with movement disorders. In his 1817 publication An Essay on the Shaking Palsy, James Parkinson was the first to describe the psychiatric symptoms of the disease that bears his name, among which apathy was later included by other authors. It was not until Edouard Brissaud, one of Jean-Martin Charcot’s disciples, that greater attention was paid to the non-motor symptoms of Parkinson’s disease, specifically apathy. Brissaud, who took charge of the Tuesday lectures at the Salpêtrière hospital between 1893 and 1895, devoted two consecutive lectures, the 22nd and 23rd, to Parkinson’s disease, where he reported psychic signs of the disease, including apathy. As Prange et al. (2018) note, for the first time in history, apathy was recognized as an independent pathological condition. Brissaud described the absolute apathy of some Parkinson’s patients as “a state of mixed indifference and absence of reaction to external and internal events… the patients do not speak any more than they move… they seem disconnected from the world around them, indifferent to everything… they remain inert in the absence of impulse, as if they needed to be provoked to react” (Brissaud, 1895).

In his description, Brissaud highlighted the lack of emotional reactivity to environmental stimuli in apathetic patients, emphasizing the affective dimension of the disorder. Moreover, with the phrase “patients do not speak more than they move…” he skillfully pointed to the association between the reduced motor behaviors of these patients (hypokinesia), which is a hallmark of Parkinson’s disease, and the reduction in their language and mental life (Prange et al., 2018). Brissaud explicitly separated apathy from depression, anxiety, and cognitive impairments, attributing it to a process of “intellectual welding” (soudure intellectuelle) that reflected the patients’ motor disability. He argued that apathetic patients remained inert in the absence of external impulses, as if they needed to be provoked to react. This similarity between motor and psychic manifestations was also reflected in amimia (lack of facial expressiveness), which mirrored the patients’ mental state. Despite the innovative nature of this perspective, Brissaud’s description of apathy in Parkinson’s disease was not internationally recognized at the time (Prange et al., 2018).

An important contribution to the conceptual framework of apathy at the beginning of the 20th century came from Karl Wernicke’s classification of behavioral syndromes in mental illness in Berlin in 1900 (Ajuriaguerra, 1971). Wernicke coined the term akinesia to describe behaviors similar to catatonia, contrasting them with opposite manifestations, such as hyperkinetic behaviors like mania. In his classification, he hypothesized that motor signs represented only the “tip of the iceberg” of internal psychic movements, which he also referred to as a “psychosis of mobility” (in Prange et al., 2018). His disciple, Karl Kleist, defined akinesia as a syndrome characterized by a lack of initiative and drive in frontal behavioral syndromes following traumatic brain injury (Ajuriaguerra, 1971), a view strikingly similar to Brissaud’s “absolute apathy.” In 1923, Friedrich Heinrich Lewy redefined akinesia in the way it is understood today, as a delay in the initiation of movement in parkinsonism (Ajuriaguerra, 1971). This was probably one of the first approaches where the reduction of initiative was directly associated with slowness in initiation (Prange et al., 2018).

Although the term apathy eventually gave rise to various other terms, its original meaning was preserved by François Naville, who, in 1922, introduced a new term: bradyphrenia. While studying the mental complications of the epidemic known as encephalitis lethargica, Naville described the syndrome of apathy, distinguishing between its motor, cognitive, and emotional components. He characterized it as: “A very frequent and peculiar state of mental fatigue and fading […] characterized by a reduction in voluntary attention, spontaneous interest, initiative, effort, and work capacity, accompanied by objective fatigue as well as a slight decline in memory” (Naville, 1922). Naville successfully differentiated the cognitive and motivational aspects of apathy in patients with Parkinson-like symptoms caused by encephalitis lethargica. He also described the symptoms associated with bradyphrenia: a slowing of thought distinct from motor slowness, contributing to an overall deceleration in action. Naville noted deficits in initiation and novelty-seeking behaviors and observed that these patients struggled more with problem-solving tasks requiring external stimulation than with tests independent of such stimulation. Furthermore, he remarked that external repeated stimulation could improve their performance. Naville explained, “It is not only the peripheral execution of movements that is slow, nor solely the time lost between the given command and the beginning of execution, but primarily and fundamentally, the distribution of commands and movements itself is slowed or, at times, suspended—something that can disappear under external stimulation.” Based on this observation, Naville drew a parallel between alterations in motor tone and the loss of “psychic tone” in post-encephalitic patients. He hypothesized that, at least in diseases affecting the basal ganglia, mental slowing was not solely due to the slow execution of movements but also to a loss of initiative and drive.

Nevertheless, the descriptions and observations made during this period could be regarded as somewhat unsystematic from today’s perspective. Various authors characterized this phenomenon in markedly different ways and generally confined their studies to mental illness. The advances in neurology, cognitive neuroscience, and neuropsychology that emerged in the second half of the 20th century significantly contributed to shaping the modern concept of apathy, which has a history of little more than thirty years.

In this regard, another turning point in the conceptualization of apathy through the study of neurological diseases occurred between the 1970s and 1990s. During these decades, research on neuropsychiatric syndromes associated with basal ganglia dysfunction, including focal lesions, led to the proliferation of various terms such as athymhormia, psychic auto-activation deficit, and pure psychic akinesia. These terms were later replaced by others, such as abulia or anhedonia (Prange et al., 2018), all of which share features with apathy. For instance, in 1982, Laplane et al. described a severe form of apathy, which they termed the syndrome of loss of psychic auto-activation, in a patient who had sustained lesions in the lenticular nuclei. Subsequently, the same research group reported three additional cases, all of which involved patients who had experienced toxic encephalopathy (Laplane et al., 1984).

The introduction of levodopa (L-DOPA) during the transition from the 1960s to the 1970s not only revolutionized the treatment of Parkinson’s disease and significantly improved patients’ quality of life but also opened a new line of research linking dopamine deficits or excesses to behavioral alterations such as apathy or behavioral disinhibition, respectively (Prange et al., 2018). Oliver Sacks was among the first to systematically describe the side effects of L-DOPA, juxtaposing motor, cognitive, and emotional symptoms with their counterparts induced by L-DOPA therapy in patients with encephalitic parkinsonism. According to Sacks, the apathy accompanied by emotional flattening observed in parkinsonism transformed into its opposite following L-DOPA therapy, leading him to coin the term “hyperpathy.” This state was characterized by increased appetite, heightened sexual arousal, irritability, aggression, and impatience (Prange et al., 2018).

Thus, a continuum of behavioral alterations was proposed, linked to insufficient or excessive dopamine levels in the fronto-subcortical circuits (Pagonabarraga et al., 2015). Among these disorders, apathy emerged as one of the non-motor manifestations associated with dopaminergic deficits. Lastly, another advancement in understanding behavioral symptoms linked to altered dopamine levels arose from the implementation of deep brain stimulation (DBS) of the subthalamic nucleus in the 1990s (Limousin et al., 1995). One of the unexpected side effects was the appearance of post-surgical apathy, which was attributed to a withdrawal syndrome from dopaminergic treatment. This syndrome, in addition to apathy, could include anxiety and depression (Thobois et al., 2010). Post-surgical apathy was associated with mesolimbic dopaminergic denervation and appeared to respond favorably to dopaminergic agonists (Pagonabarraga et al., 2015), further emphasizing the relationship between dopamine-rich structures, such as the basal ganglia and prefrontal cortex, and apathy.

Contributions such as those mentioned above highlight the intriguing parallelism between the motor and psychic domains, an idea elegantly pointed out by authors like Brissaud in movement disorders (Brissaud, 1895) and Dide and Guiraud in patients with schizophrenia (Dide & Guiraud, 1922). Just as motor movements are impossible without muscle tone, these authors implicitly suggest the necessity of an optimal “psychic tone” to facilitate the initiation of emotions and cognitions.

Beyond movement disorders, apathy was also described in the late 20th century in other focal neurological conditions, such as stroke. One notable example is patients with the rare bilateral thalamic infarction, also known as Percheron syndrome or paramedian diencephalic syndrome (Laplane, 1984; Meissner et al., 1987; Engelborghs et al., 2000). These patients commonly exhibit vertical gaze palsy, arousal deficits, and severe anterograde amnesia with confabulations (Meissner et al., 1987). A particularly striking feature in these cases is a profound impairment in “psychic self-activation,” often accompanied by initial drowsiness (Engelborghs et al., 2000).

Finally, it is worth highlighting the contribution of Jeffrey L. Cummings’s review of the different frontal syndromes. In his manual Frontal-Subcortical Circuits and Human Behavior (Cummings, 1993), he synthesizes the behavioral effects of lesions in the frontal lobe and related subcortical structures (basal ganglia and thalamus). While apathy is associated with lesions in the dorsolateral prefrontal cortex (and the subcortical regions connected to it), this impairment takes on particular significance in the so-called anterior cingulate syndrome. When lesions are bilateral, this syndrome is characterized by severe akinetic mutism: “Patients are profoundly apathetic. They usually keep their eyes open, do not speak spontaneously, and respond to questions, if at all, with monosyllables. They move very little, are incontinent, and eat and drink only when fed. They exhibit no emotion, even in response to painful stimuli, and are indifferent to their own circumstances.” (Cummings, 1993).

In summary, the medical and scientific study of apathy and related conditions dates back to the early 19th century, with investigations into the behavioral disturbances of patients with schizophrenia on one hand, and those with neurological diseases on the other. Over the past two centuries, but especially since the early 20th century, analogous or at least closely related conditions to the modern conceptualization of apathy were described, and possible etiopathogenic mechanisms of the disorder were even proposed. Table 1 lists some of the clinical concepts most closely associated with apathy.

One of the most influential conceptual frameworks in recent decades was introduced by Robert Marin in the early 1990s. Based on extensive clinical observation across various neurological and psychiatric disorders, Marin operationalized apathy as a “loss of motivation, relative to a previous level, that is not attributable to emotional distress, cognitive impairment, or diminished level of consciousness.” In his model, apathy manifested in three partially dissociable components: reduced productivity (behavior), restricted goal-setting (cognition), and diminished emotional responses to success and failure (emotion) (Marin, 1990, 1991). Although he did not clearly define the organization of the different dimensions or the potential existence of a hierarchy among them,

these three dimensions, with certain refinements and additional aspects—such as the social dimension (Ang et al., 2017)—are now present in nearly all contemporary definitions of apathy, as well as in the scales used to assess it (Miller et al., 2021; Robert et al., 2009, 2018; Starkstein et al. 2000).

A second major contribution by Marin, reflected in his definition of apathy, was the proposal to consider it a distinct nosological entity and, therefore, a primary condition. Rather than viewing apathy merely as a consequence or secondary symptom of disorders such as depression, schizophrenia, or transient confusional states, he conceptualized it as a motivational syndrome with its own underlying pathophysiological mechanisms (Marin et al., 1990, 1991).

Other authors, such as Levy and Dubois (2006), argue that apathy is not a unitary construct but rather a phenomenon that can arise from different lesion topologies, leading to reduced goal-directed behavior. Building upon Marin’s three-dimensional model, they proposed three subtypes of apathy, each associated with distinct neurocognitive mechanisms: (1) affective-emotional apathy, linked to lesions in the ventromedial and orbitofrontal cortex, as well as subcortical structures connected to these regions; (2) cognitive-executive apathy, associated with lesions in the lateral prefrontal cortex and its related subcortical structures; and (3) auto-activation apathy, resulting from extensive lesions affecting anterior circuits or bilateral frontomedial damage, characterized by a marked reduction in the spontaneous generation of thoughts, emotions, and behaviors. This conceptualization of apathy departs from the traditional notion of “motivation,” which is considered a psychological construct that is challenging to operationalize and can only be inferred from observable behavior (Levy & Dubois, 2006). Consequently, more recent definitions have replaced “reduced motivation” with “a reduction in goal-directed activity” (Robert et al., 2018).

Regardless of the theoretical framework adopted, recent literature increasingly recognizes apathy as a transdiagnostic entity that cuts across traditional disease boundaries (Robert et al., 2018; Husain & Roiser, 2018). There is growing evidence suggesting that the neuroanatomical regions and circuits implicated in apathy are, at least in part, shared across different neurological disorders, psychiatric conditions, and even in healthy aging. A meta-analysis by Yan et al. (2023) identified a significant association between apathy and structural and functional alterations in the putamen and caudate across multiple disorders. Furthermore, structural neuroimaging studies revealed atrophy in the bilateral precentral gyrus, bilateral insula, bilateral medial frontal gyrus, bilateral inferior frontal gyrus, left caudate/putamen, and right anterior cingulate cortex. These fronto-striatal regions and circuits, the authors note, are associated with executive functions (e.g., planning and goal generation), reward processing, and the integration of affective and cognitive aspects for behavioral control (Yan et al., 2023).

Thus, there is now broad consensus that apathy should be regarded as a transdiagnostic entity that can manifest either as a symptom or sign of other conditions or as an independent syndrome. It affects multiple dimensions and may present with distinct clinical features depending on the lesion topology and the specific cognitive and emotional mechanisms involved. This perspective highlights the potential value of a comparative approach to studying diseases in which apathy frequently occurs, along with its associated symptoms. Such an approach may provide critical insights into the pathophysiological mechanisms underlying this potentially heterogeneous condition.