Catatonia and autism spectrum disorder: A common comorbid syndrome or a core feature?

Abstract

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder marked by persistent deficits in social communication and interaction, alongside restricted, repetitive patterns of behaviors (RRB), interests, or activities. It often co-occurs with various neuropsychiatric disorders, though their frequency varies widely due to unclear boundaries between the core features of ASD and common comorbidities. Catatonia, increasingly noted in neurodevelopmental conditions like ASD, shares striking similarities with ASD in symptomatology, brain mechanisms, and treatment responses, prompting the question of whether it is a core feature of ASD or a distinct condition. This paper delved into this overlap, exploring the relationship between catatonia and ASD through a narrative review of peer-reviewed literature from 1943 to 2024, sourced from PubMed and psychiatric journals. Focusing on ASD diagnostic evolution, symptom overlap with catatonia, and shared neurobiological and therapeutic characteristics, we used thematic analysis to synthesize findings into key areas such as historical nosology, phenomenological overlap, neurobiological parallels, and treatment response. The evidence revealed weak support for separating catatonia from overlapping RRB features of ASD, suggesting that some RRB might align more with comorbid catatonia than intrinsic ASD traits. However, this idea needs further validation through rigorous clinical trials. Clarifying this relationship could refine diagnostic approaches and open doors to targeted treatments, potentially improving outcomes for those affected.

Key Words: Catatonia; Autism spectrum disorder; Psychopathology; Electroconvulsive therapy; Stereotypies; Mannerisms

Core Tip: Catatonia and autism spectrum disorder (ASD) share similarities in phenomenology, neurobiology, and treatment response, with catatonia occurring frequently with ASD. Evidence linking these shared features to the core definition of ASD remains weak. Viewing catatonia as a distinct comorbid condition offers a more convincing framework. ASD and catatonia can be differentiated by detecting changes in severity or patterns to identify catatonia. Yet this leaves chronic, unchanging cases unresolved. Resolving this distinction is crucial for clinical care and research, as it could reveal new treatment options, like lorazepam or electroconvulsive therapy, for restrictive and repetitive behaviors in ASD, which were previously dismissed as intrinsic and untreatable due to their persistence.

INTRODUCTION

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction in addition to restricted, repetitive patterns of behaviors (RRB), interests, or activities[1]. The nosology of ASD has undergone several changes over the last 100 years, following the broader changes in general psychiatric nosology and the recognition of wide variation in disease severity and comorbidities.

ASD is commonly comorbid with several neuropsychiatric disorders, and the prevalence of these comorbidities varies widely, partly due to difficulty delineating between core features of ASD and comorbidities. Mannion and Leader[2] found that 46.1% of children and adolescents with ASD have comorbid conditions, but when intellectual disability was added, this prevalence rose to 78.7%. These comorbidities include attention deficit hyperactivity disorder in 50%-90%[3,4], major depressive disorder or bipolar disorder in 30%[5], anxiety and obsessive-compulsive disorder in 2%-40%[6], epilepsy in 30%[7], gastrointestinal symptoms in 9%-91%, sleep problems in up to 80%[8], and intellectual disability among 30% of ASD patients[9].

Concurrently, catatonia has prominent affective, cognitive, motor, and behavioral manifestations[10]. Catatonia is common among patients with structural central nervous system abnormalities and developmental disorders, with the combined rate of catatonia at 11.6%[11]. ASD is among the neuropsychiatric disorders with a high frequency of catatonia, with recent studies estimating the frequency to be 4%-17%[12].

Catatonia shares significant phenomenological and clinical overlap with the domain of RRB, interests, or activities in ASD. This can be elucidated in presentations like manneristic speech, manneristic and stereotypical behaviors, echolalia, echopraxia, perseveration, verbigeration, posturing, rituals, and compulsions. Other features, such as excitement and agitation, are seen in both disorders despite not being a core feature of ASD. In addition to the clinical features, ASD and catatonia share overlapping neurobiological features and similar responses to the treatment modalities, such as lorazepam and electroconvulsive therapy (ECT)[13-15].

The extensive similarities between catatonia and ASD in their nosological development, increased prevalence of catatonia in ASD populations, overlap in clinical presentation, neurobiology, and response to treatment modalities spark a pivotal question: Are these repetitive behaviors an intrinsic part of ASD, or do they signal comorbid catatonia? To unravel this, we conducted a narrative review of literature from 1943 to 2024, sourced from PubMed and psychiatric journals. We synthesized the literature on ASD and catatonia using Braun and Clarke’s six-step thematic analysis framework[16]. We identified recurring concepts through iterative reading and generated initial codes [e.g., 'echolalia', 'γ-aminobutyric acid (GABA) dysfunction']. These were grouped into provisional themes aligned with our aims: Tracing historical nosology; analyzing phenomenological overlap; and evaluating their distinction as separate entities. These themes were refined by cross-checking the literature, resulting in four final themes: Historical nosology; phenomenological overlap; neurobiological parallels; and treatment response. These were integrated into a narrative synthesis, supported by examples such as the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-TR criteria and SHANK3 mutation studies, to explore the ASD-catatonia relationship.

Early insights suggest the line between ASD’s RRB and catatonia blurs. RRB often resemble catatonic features, hinting they might lean more toward a separate condition than a core trait. Resolving this could reshape diagnosis and unlock targeted therapies, though their safety in ASD remains a cautious frontier needing deeper study.

HISTORICAL BACKGROUND OF ASD NOSOLOGY

Early concepts

Both ASD and catatonia were assimilated into schizophrenia until DSM-III when ASD became a separate condition within developmental disorders[17]. Catatonia, on the other hand, was a subtype or a presentation related to schizophrenia until DSM-5 when it was finally recognized as a specifier to several psychiatric and medical conditions[18].

The development of ASD nosology followed an interesting path. Early descriptions of ASD started with Bleuler[19] in 1911, who described symptoms in severe cases of schizophrenia. Based on predominant theories of that era on putative psychodynamic mechanisms, Bleuler provided the term “autism” to describe a hypothesized state of infantile wishes to avoid unsatisfying realities and replace them with fantasies and hallucinations[20]. This term was imprecise in distinguishing between what would become known as ASD and early-onset schizophrenia.

By 1943, Kanner[21,22] was the first to separate autism from childhood schizophrenia following the careful observation of 11 children who had a typical pattern of extreme aloneness from the beginning of life and an anxiously obsessive desire for the perseveration of sameness. Kanner[21,22] agreed with some aspects of Bleuler’s initial description of the withdrawal from reality but hypothesized that patients with autism engaged in withdrawal willingly and surrendered themselves to a fantasy. He also believed that children with autism never developed the capacity to interact appropriately with the external world, distinguishing them from children who suffered regression due to another cause. In addition, Kanner[21,22] hypothesized that individuals with ASD developed a unique and relatively unskilled relationship with the intimate external environment, thus separating it from the withdrawal of the external world described by Bleuler[19]. Kanner[21,22] excluded children with known genetic syndromes, brain injuries, or severe intellectual disability when diagnosing children with autism.

In 1949, Mahler[23] described a syndrome of “symbiotic infantile psychosis” in children she believed made desperate efforts to avoid the catastrophic anxiety of separation, focusing on attachment theory, which was different from Kanner’s conceptualization of autism. In 1964, Rimland[24] attempted to refine autism diagnostic criteria by creating a checklist that had 109 items that covered several aspects of developmental history and milestones, peculiarities about interactions with the external world, and several symptoms that are currently recognized under the RRB domains, such as rituals, verbigeration, and echolalia.

Leonhard[25] studied children with psychomotor psychosis and catatonia. He suggested that catatonia during childhood only occurs among infantile schizophrenia, a rare variant of schizophrenia that appears during childhood. This was thought to progress to systematized schizophrenia, a form equivalent to some cases of adult-onset schizophrenia. He also recognized that infantile autism, which Kanner described, was a competing concept to his infantile schizophrenia hypothesis. Hence, he suggested that children with schizophrenia are seen “to have no soul, and nothing can be inferred from their facial expressions, while those with infantile autism have a different soul”[26]. DSM-III accepted both diagnoses, but due to the considerable overlap in criteria, it led to poor recognition of autism disorder during that period[27].

DSM evolution and the shadow of schizophrenia

Despite all the progress in the development of the recognition of autism, the second edition of the DSM, which was released in 1968, continued to recognize autism under schizophrenia, childhood type and was characterized by "atypical withdrawal behavior", "failure to develop identity separate from the mother's", and "general unevenness, gross immaturity, and inadequacy in development" highlighting the influence of psychoanalytic ideas on the term autism[28].

In 1978, Rutter[29] modified the original criteria proposed by Kanner and suggested a conceptual definition of autism that included delayed and deviant social and language abilities, general developmental level, restricted interest, and repetitive behavior. Rutter’s definition was influential on the advent of the DSM-III[29]. Interestingly, Rutter’s definition separated restricted interest from repetitive behavior[29].

Following extensive research that accumulated after the DSM-II era, the DSM-III finally distinguished between childhood-onset schizophrenia and autism in 1980[17]. DSM-III described autism as a pervasive developmental disorder (PDD) and defined three essential features of autism: A lack of interest in people; severe impairments in communication; and bizarre responses to the environment. These features develop in the first 30 months of life[17]. The definition of infantile autism was monothetic and required all criteria to be met. This produced some limitations in the sensitivity, and the term infantile provided a less developmentally focused approach. With further studies, autism was considered a heterogeneous disorder with significant presentation diversity, comorbidities, and severity[2].

Refining the identity of autism

The DSM-III-R moved from the term “infantile autism” to “autistic disorder” as the name for the condition to reflect a more flexible and developmentally oriented approach. In addition, the DSM provided a dimensional approach to reflect this heterogeneity and provided a polythetic set of 16 criteria. To simplify the complexity stemming from the heterogeneity in symptom range and severity, a model was created to organize these symptoms based on clinical judgment of these symptoms’ similarities into three major domains: (1) Qualitative impairments in reciprocal social interaction; (2) Impairment in communication; and (3) Restricted interest/resistance to change and repetitive movements. This approach was later criticized for being arbitrary and not supported by an empirical factor structure[30,31]. The diagnosis required the presence of eight positive criteria, two from the social domain and at least one from each of the other two domains. They also changed the onset requirement from 30 months to 36 months[31]. Table 1 summarizes DSM-III-R diagnostic criteria for autism disorder. PDD-not otherwise specified was used for patients who did not fulfill all the criteria for autism disorder.

Table 1 Summary of Diagnostic and Statistical Manual of Mental Disorders-III-R diagnostic criteria for autism disorder.

Qualitative impairments in reciprocal social interaction	Impairment in communication	Restricted interest/resistance to change and repetitive movements
Lack of awareness	No communication	Stereotypies
Seeking comfort	Abnormal nonverbal	Parts of objects
Imitation	Imaginative activity	Environmental change
Social play	Production-speech	Insistence-routine
Peer friendship	Form/content-speech	Restricted interests
	Conversation

When DSM-IV, initially released in 1994, was revised in 2000 to form DSM-IV-TR, the language was changed to recognize autism as a spectrum[32,33]. In addition, different assessment tools were used for research in preparation for the DSM-IV. They used factor analysis, a multivariate statistical method used to evaluate relationships among a set of observed variables, to reduce the heterogeneity of symptoms. Several models produced a different number of dimensions. The first was the traditional three-factor group. The second group was a two-factor (social/communication and restricted behaviors). Finally, a five-factor model (social, communication, restricted interests, stereotyped mannerisms, and adherence to routine) was established.

The basis for assigning many of these ASD symptoms under suggested domains in both DSM-IV and DSM-IV-TR was cluster analysis[34]. Cluster analysis can minimize the effect on homogeneity by grouping the sample items based on similarities and differences. This method can produce several benefits, such as developing diagnostic criteria, explaining heterogeneous outcomes, and tailoring treatment to subgroups. Despite the importance of cluster analysis, especially in developing domains related to ASD, cluster analysis cannot differentiate between core features of the illness and common comorbidities with similar presenting symptoms[35].

DSM-IV and beyond

To avoid conflicts with international collaboration and studies, the DSM-IV followed the steps of the International Classification of Diseases-10. It continued to use the traditional three-category or dimensions model, with a final set of criteria that needed to be more numerous and detailed. In addition, it followed the International Classification of Diseases-10 and listed five disorders with distinct features, including Asperger’s disorder, childhood disintegrative disorder, and Rett syndrome in addition to ASD and PDD not otherwise specified[32]. Both DSM-IV and DSM-IV-TR require the delay or abnormal function in at least one of the following areas, with onset to age 3 years: (1) Social interaction; (2) Language as used in social communication; and (3) Symbolic or imaginative play. Table 2 summarizes DSM-IV and DSM-IV-TR diagnostic criteria for ASD.

Table 2 Summary of the Diagnostic and Statistical Manual of Mental Disorders-IV and Diagnostic and Statistical Manual of Mental Disorders-IV-TR diagnostic criteria for autism spectrum disorder.

Qualitative impairment in social interaction, as manifested by two of the following	Qualitative impairment in communication as manifested by at least one of the following	Restricted repetitive and stereotyped patterns of behavior, interest, and activities, as manifested by at least one of the following
Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body posture, and gestures that regulate social interaction	Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gestures or mime)	Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal either in intensity or focus
Failure to develop peer relationships appropriate to the developmental level (e.g., by a lack of showing, bringing, or pointing out the object of interest)	In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others	Inflexible adherence to specific, nonfunctional routines or rituals
Lack of social or emotional reciprocity	Stereotyped and repetitive use of language or idiosyncratic language	Stereotyped and repetitive motor manners (e.g., hand or finger flapping or twisting or complex whole-body movement)
	Lack of varied, spontaneous make-believe play or social imitative play appropriate to the developmental level	Persistent preoccupation with parts of objects

In 2013, DSM-5, and later DSM-5-TR, adopted the concept of ASD, moving from a multicategorical diagnostic system into a single diagnosis, collapsing autism, Asperger Syndrome, Rett Syndrome, and childhood disintegrative disorder into a single diagnosis, in addition to unspecified neurodevelopmental disorder[1,18]. This approach was reported to have adequate sensitivity and specificity[36]. They also reduced the previous three-domain symptom model into a two-domain symptom model by combining the communication and social symptom categories into a single social-communication domain, keeping the RRB domain separate. This change was driven by factor analysis results that supported combining social and communication into a single domain and recognizing that categorizing behaviors as social or communicative may be an arbitrary division. The DSM-5 and DSM-5-TR provided a core symptom domain for the severity level of support needed for individual functioning and specifiers that offer descriptions of common co-occurring non-ASD impairment, such as intellectual impairment, language deficits, and medical and psychiatric disorders[37-39].

The DSM-5-TR diagnostic criteria for ASD recognize several psychopathological deficits across two domains of function. The first domain is social communication and interaction, where deficits exist across several contexts in social-emotional reciprocity, non-verbal communications, and developing, maintaining, and understanding relationships. The second domain is RRB patterns, interests, or activities. Within this domain, four areas of deficits are recognized. The diagnosis requires the presence of deficits in at least two of the four areas: (1) Stereotyped or repetitive motor movements, use of objects, or speech; (2) Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior; (3) Highly restricted, fixated interests that are abnormal in intensity or focus; and (4) Hyper-reactivity or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment[40]. Table 3 presents DSM-5-TR criteria for ASD.

Table 3 Summary of the Diagnostic and Statistical Manual of Mental Disorders-5 and Diagnostic and Statistical Manual of Mental Disorders-5-TR diagnostic criteria for autism spectrum disorder.

Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the current or by history	Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following
(1) Deficits in nonverbal communicative behaviors used for social interaction, ranging from poorly integrated verbal and nonverbal communication to abnormalities in eye-to-eye contact and body language, or deficits in understanding and use of gesture, to total lack of facial expression and nonverbal communication	(1) Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys, or flipping objects, echolalia, idiosyncratic phrases)
(2) Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties in behavior to suit various social contexts, difficulties in sharing imaginative play or making friends, to the absence of interest in peers	(2) Insistence on sameness, inflexible adherence to routine, ritualized patterns, or verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take the same route, or eating daily)
(3) Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts, to difficulties in sharing imaginative play or making friends, to an absence of interest in peers	(3) Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to preoccupation with unusual objects, excessively circumscribed or perseverative interests)
	(4) Hyper-reactivity or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement)

CATATONIA AND ASD OVERLAP

Existing nosological structures do not adequately distinguish RRB of neurodevelopmental disorders from motor and behavioral features of catatonia, and historical structures conflated both with schizophrenia. Cluster analysis, while shaping domains of ASD, struggles to separate intrinsic traits from co-occurring conditions like catatonia, setting the stage for reevaluating their relationship. This section will discuss the overlap between catatonia in phenomenology, neurobiology, and the response to similar treatment modalities.

Catatonia phenomenology

Catatonia was also previously linked to schizophrenia, and this position continued to dominate the field from Kraepelin until DSM-5[18,41-43]. In contrast to the older views of catatonia being related to schizophrenia, catatonia is commonly observed in the course of various psychiatric disorders, particularly bipolar disorder and depression[43]. Catatonia is also seen among several degenerative and demyelinating neurological diseases, such as Parkinson’s disease[44], multiple sclerosis, and epilepsy[45]. Oldham[11] suggested that the combined rate of catatonia among patients with structural abnormalities in the central nervous system and developmental disorders is nearly 11.6%. In addition, catatonia is frequently observed among patients with neurodevelopmental disorders such as ASD, with prevalence estimated to be between 4%-17%[12]. Catatonia is also described in the course of several medical conditions. As a result, both DSM-5 and DSM-5-TR recognized catatonia as a specifier that occurs with several psychiatric disorders and medical conditions[1,18].

While catatonia is commonly recognized as a psychomotor syndrome[10,46], a more comprehensive view recognizes catatonia as a syndrome with prominent psychomotor and cognitive manifestations. This article focused on the current catatonia nosology rather than its historical and affective manifestations[9]. Current DSM-5-TR criteria focus on motor and behavioral presentations with features such as mutism, posturing, stupor, grimacing, mannerism, stereotypies, echolalia, echopraxia, negativism, excitement, waxy flexibility, and catalepsy[34]. Table 4 summarizes the current DSM-5-TR diagnostic criteria for catatonia.

Table 4 Symptoms of catatonia based on the Diagnostic and Statistical Manual of Mental Disorders-5-TR.

Catatonia symptoms	Definitions
Mutism	No or very little verbal response (excluding known aphasia)
Posturing	Spontaneous and active maintenance of a posture against gravity
Stupor	No psychomotor activity; not actively relating to the environment. An extreme manifestation of the previous phenomena
Agitation	Emotionally restless, not as a result of external stimuli
Waxy flexibility	Slight, even resistance to positioning by the examiner
Catalepsy	Passive induction of a posture held against gravity
Echolalia	Mimicking another’s speech
Echopraxia	Mimicking another’s movements
Negativism	Opposition or no response to instruction or external stimuli. Negativism can be a complex behavior
Stereotypies	Repetitive, abnormally frequent, non-goal-directed movements
Mannerisms	Odd, circumstantial caricature of normal actions
Grimacing	Displaying contorted facial expressions

Other clinical catatonia scales have been developed for diagnosis and monitoring[47]. These scales are the Bush Francis Catatonia Rating Scale[48], Modified Rogers Scale[49], Rogers Catatonia Scale[50], Northoff Catatonia Rating Scale[10], Kanner Scale[51], Brauning Catatonia Rating Scale[52], and the Pediatric Catatonia Rating Scale[53]. Table 5 summarizes all catatonia presentations in the Bush Francis Catatonia Rating Scale, Modified Rogers Scale, Rogers Catatonia Scale, Northoff Catatonia Rating Scale, Kanner, Brauning Catatonia Rating Scale, and Pediatric Catatonia Rating Scale with the overlap between these catatonia presentations and Diagnostic and Statistical Manual of Mental Disorders-5-TR diagnostic criteria for autism spectrum disorder.

Table 5 List of catatonia symptoms reported by the Diagnostic and Statistical Manual of Mental Disorder-5-TR and catatonia clinical scales (Bush Francis Catatonia Rating Scale, Modified Rogers Scale, Rogers Catatonia Scale, Northoff Catatonia Rating Scale, Kanner Scale, Brauning Catatonia Rating Scale, and Pediatric Catatonia Rating Scale), with the overlap between these catatonia presentations and Diagnostic and Statistical Manual of Mental Disorders-5-TR diagnostic criteria for autism spectrum disorder.

Overlapping features of catatonia on the DSM-5-TR and the (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS) scales	Corresponding similar or related symptoms in ASD based on the DSM-5-TR criteria and other features reported in ASD
Echolalia/echopraxia (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS)	Reported
Stereotypy (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS)	Reported
Mannerism (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS)	Reported
Excitement (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS)	Reported
Grimacing (BFCRS, NCRS, Kanner, BCRS, and PCRS)	Reported (facial mannerisms/stereotypies)
Verbigeration (BFCRS, MRS-C, RCS, NCRS, Kanner, BCRS, and PCRS)	Reported
Impulsivity (BFCRS, NCRS, Kanner, BCRS, and PCRS)	Reported
Combativeness (BFCRS, Kanner)	Reported
Perseveration (BFCRS, NCRS, Kanner)	Reported
Abnormal speech (MRC-S, RCS, NCRS)	Reported
Rituals (MRC-S, NCRS)	Reported
Compulsive behaviors (NCRS, PCRS)	Reported
Compulsive-like speech (NCRS)	Reported

BFCRS: Bush Francis Catatonia Rating Scale; MRS-C: Modified Rogers Scale-Catatonia Subscale; NCRS: Northoff Catatonia Rating Scale; BCRS: Brauning Catatonia Rating Scale; PCRS: Pediatric Catatonia Rating Scale; RCS: Rogers Catatonia Scale; DSM: Diagnostic and Statistical Manual of Mental Disorders; ASD: Autism spectrum disorder.

Examining all the various presentations in the DSM-5-TR catatonia criteria and the various clinical scales show a noticeable degree of overlap in symptoms. In addition, multiple presentations of similar or identical catatonic phenomena are captured under different terms, such as catalepsy and posturing, mitgehen, mitmachen and magnetism, withdrawal and negativism, impulsivity, excitement, and agitation. Another challenge in recognizing and diagnosing catatonia is the lack of consistency in describing presentations of mannerisms and stereotypies and the various complex manifestations of these phenomena, such as grimacing, increased blinking, compulsive behaviors, compulsive speech, and verbigerations.

Catatonia and ASD phenomenological overlap

Several catatonia symptoms are also described as part of the core features of ASD, especially among the RRB and action domains of ASD. Examples of symptoms that would fall under this category include stereotypies of speech (echolalia, idiosyncratic language, perseverative language, or repetitive vocalizations such as grunting or humming) as well as stereotypical motor movements, which range from repetitive movements of hands (clapping, flapping, etc.) to complex whole-body movements, intense body tensing, facial grimacing, and other perseverative actions. These symptoms and behaviors do not just resemble symptoms described in catatonia but rather are clinically identical (Table 5). Mahgoub et al[54] discussed the inconsistencies in the psychiatric literature regarding the descriptions of mannerisms and stereotypies. They highlighted the varying definitions provided in different editions of the DSM for these phenomena, which are addressed under various conditions such as catatonia, ASD, and stereotypical movement disorders. The authors proposed that these activities are not limited to simple motor movements; they can also encompass complex behaviors, including repetitive and fixated eating and drinking. Additionally, they noted behaviors typically observed in patients with ASD, such as repetitive self-harm and mutilation, can be considered as stereotypies.

Mahgoub et al[54] suggested that evaluating complex behaviors within their appropriate context, including the patient’s typical or prior behavioral norms, could help link these behaviors to underlying pathological processes. This approach may provide clinicians with more effective methods for recognizing complex or unique behavioral presentations of catatonia similar to polydipsia and polyphagia.

Finally, they proposed distinct definitions: Mannerisms as non-contextual, fixated peculiarities of behavior; and stereotypies as non-contextual, repetitive activities. They argued that incorporating context and describing patterns can enhance understanding of these phenomena, particularly when describing complex activities observed in ASD and catatonia.

Other catatonic features include some other presentations that are seen in both ASD and catatonia, such as agitation, excitement, and impulsivity (Figure 1). The criterion in the diagnosis of ASD is deficits in social communication, and while it has been posited that negativism, withdrawal, and mutism of catatonia resemble these social deficits, the typical onset and acuity of mutism in catatonia is different from baseline chronic mutism that can be seen in ASD. In addition, deficits in social-emotional reciprocity do not provide an adequate parallel to negativism due to the differences inherent in the early onset and lifelong nature of ASD compared to the more acute changes often seen in catatonia.

Figure 1 Overlap of autism spectrum disorder restricted repetitive behaviors and catatonia symptoms. ASD: Autism spectrum disorder.

The degree of overlap between many of the described features of the restrictive repetitive behaviors domain and several other presentations described in ASD, with presentations described in catatonia, has been described in the psychiatric literature as posing a significant diagnostic challenge[55]. Such similarities raise the question of their independence and whether both disorders are separate.

Neurobiological overlap of catatonia and ASD

Despite continual advancement, research regarding the neuroscience of disorders like catatonia and ASD is in its infancy; common trends can be noted across the disparate literature. Through empirical study, it has been proposed and supported that GABA-A hypofunction, dopamine hypoactivity at the D2 receptor, and glutamate hypoactivity at the N-methyl-D-aspartate (NMDA) receptor have the potential to predispose, initiate, and maintain catatonia and the related neuroleptic malignant syndrome[56]. GABA-A agonists and NMDA antagonists may ameliorate catatonia, while it can be initiated or worsened with D2-blocking antipsychotics.

At the circuit level, imaging studies in hypokinetic catatonia show hyperactivity of premotor areas related to cortico-cortical or cortico-basal ganglia loops[57-59]. Similar motor pathways are implicated in analogous research on stereotypies in ASD[60]. In addition to imaging studies suggesting the importance of specific sites like the premotor areas, anterior cingulate cortex, and orbitofrontal cortex in catatonia, emerging genetic research is showing how intracellular scaffolding and support proteins such as SHANK3 and MLC1 represent significant predisposing factors to both sporadic and periodic catatonia, respectively[61,62]. Interestingly, these same genes are implicated in genetic syndromes in which ASD is a common feature[63,64]. Furthermore, multiple genetic syndromes associated with autism feature mutations in genes related to diverse synapse functioning, such as neuroligin 3, neuroligin 4, various synapsis, and notably subunits of the GABA-A and NMDA receptors[65].

Dhossche et al[66] studied three subjects with SHANK3 gene mutations or intragenic deletion and followed them for the emergence of psychomotor phenomena. All 3 patients showed various combinations of catatonic features during their lives, including posturing, psychomotor slowdown, prompt responses, pseudocompulsion, negativism, stereotypies, mannerisms, mutism, echolalia, echopraxia, ambitendency, and verbigeration. Their study supported the link between SHANK3 mutations and childhood catatonia, especially among children with neurodevelopmental disorders, such as ASD.

The common genetic vulnerabilities reinforce an intimate relationship between ASD and catatonia. However, aberrations in these same genes and pathways are also implicated in other neuropsychiatric disorders, such as intellectual disability and epilepsy[67].

While emerging genetic research highlights shared vulnerabilities (e.g., SHANK3, MLC1) and neurobiological overlaps (e.g., GABA-A and NMDA receptor dysfunction), these findings remain preliminary. Robust empirical studies, such as genome-wide association studies or functional imaging trials, are needed to confirm these links and distinguish them from broader neuropsychiatric patterns seen in epilepsy or intellectual disability.

Shared response to similar modalities of treatment

Catatonia has been increasingly recognized in the last two decades among patients with ASD, with the focus on treating symptoms of motor and verbal mannerisms, echolalia, ritualistic behavior, obsessive preoccupation, excitement, aggression, impulsivity, and stereotypical self-harm behavior. The positive response to lorazepam was reported in several studies[68-73], and the role of ECT in treating catatonia in patients with ASD was also discussed extensively[15,74-77].

Some presentations in patients with ASD, such as repeated self-injurious behaviors, which are not classically characterized as related to catatonia, respond adequately to ECT[14,78,79]. Given its non-contextual repeated activity, repeated self-injurious behavior can be categorized as a complex form of catatonic stereotypy. This may explain the excellent response to ECT.

With the significant overlap between catatonia and ASD diagnostic criteria, several authors attempted to address these diagnostic challenges, and some approaches were suggested. One approach suggested that catatonia should be suspected when there is a change in the type or pattern of premorbid functioning or prior established symptoms[80]. Nordgaard et al[81] supported this approach. They emphasized a delineation between state and trait disorders, whereby one condition may be chronically present and inform all aspects of life, while another may periodically present with circumscribed episodes. Furthermore, the author and others argue compellingly in favor of hierarchical psychiatric nosologies; the compartmentalization of discrete symptom clusters is reduced to understand the patient experience more holistically[80,82].

Other authors suggested using the term autistic catatonia, which describes patients with ASD who present with prominent negativism and psychomotor retardation for over 1 month that involves freezing when carrying out actions, very slow voluntary movements, stopping the course of movements, and requiring prompting to complete actions[83]. This concept was modified later to suggest that odd gait, odd stiff posture, mutism, impulsive actions, incontinence, and excitement are more likely to suggest catatonia when observed among patients with ASD[84]. Most of the studies that showed a response to lorazepam or ECT recognized catatonia in ASD patients by observing changes in prior patterns and course of illness. Such an approach leaves a remaining question about patients with ASD who have a stable course and pattern of overlapping symptoms that might still be framed as catatonia and respond to lorazepam and ECT.

The case for distinguishing catatonia from overlapping features of ASD lacks strong empirical support, particularly in neurobiology, where data are suggestive but not definitive.

Evidence for overlap

ASD and catatonia share extensive phenomenological, neurobiological, and therapeutic parallels. RRB, like echolalia and stereotypies, are clinically identical to catatonic features, and both respond to similar interventions. Neurobiological links, though preliminary, reinforce this connection. Hence, it is essential to provide more details about the concept of comorbidity and the standard used in the DSM to separate overlapping conditions.

COMORBID OR OVERLAPPING DISORDERS?

The concept of comorbidity

Feinstein[85] was the first to discuss the concept of comorbidity. He defined comorbidity as a distinct additional clinical entity that has existed or may occur during the clinical course of a patient with the index disease under study. Feinstein’s concept was based on the notion of distinct additional clinical entities and most importantly that a medical condition must have either known etiology or circumscribed pathology to qualify as a distinct additional clinical entity[85,86]. With the development of DSM-III, the concept of comorbidity was also used to describe the co-occurrence of two or more mental disorders[87]. However, applying Feinstein’s definition in psychiatry was challenging compared to other branches of medicine, as most psychiatric disorders do not have a well-circumscribed psychopathology or biomarkers that can be equivalent to the pathology in Feinstein’s model. In addition, many psychiatric disorders are not demarcated from each other due to symptom overlap. Hence, the notion of distinct clinical entities is lacking in psychiatry[75,88].

The application of the concept of comorbidity in psychiatry resulted in three forms of outcomes. The first is true comorbidity, which matches Feinstein’s requirement for distinct additional clinical entities. The second is artificial comorbidity, commonly seen in the DSM due to the split and categorical system applied, where overlapping symptoms might suggest the presence of two diagnoses. Finally, spurious comorbidity can be detected, as in the examples of autistic disorder and Asperger’s disorder in DSM-IV[89].

Several approaches have been utilized to improve diagnostic validity and reduce artificial and spurious comorbidity. The Robins and Guze[90] diagnostic (construct) validity served as the basis for DSM-III diagnoses in clearly delineating several disorders as clinically distinct criteria. These criteria are: (1) Clinical description: Identification and description of the syndrome, either by clinical intuition or by cluster analysis. Cluster analysis was used extensively to validate clinical criteria and descriptions. However, the criteria used for cluster analysis should be the best discriminators. As discussed above, cluster analysis needs to be able to differentiate between core features and common comorbidities; (2) Exclusion of other disorders: This is important to show boundaries or points of rarity between related syndromes. While relevant, this point must be achieved to differentiate between many psychiatric syndromes; (3) Follow-up study: To assess the presence of distinct courses over time and therapeutic trials showing distinct treatment responses; (4) Family study: To assess the genetics or hereditability aspects of the illness; and (5) Laboratory study: This identifies neurobiological or pathological aspects of the disorder being assessed, including psychological, genetic, molecular, histological, and radiological factors[90,91].

Challenges in separation

As we attempt to apply these criteria to ASD in relationship to catatonia, it becomes evident that many of the suggested criteria for diagnostic validity are not met, as the clinical description shows significant overlap in symptoms, especially in the domain of RRB such as the various presentations of mannerisms, stereotypies, echolalia, perseveration, excitement, and various obsessive behaviors. While it is not uncommon to have overlapping presentations between various psychiatric disorders, these symptoms are identical in both disorders to the degree of making the second criterion of exclusion of other disorders, catatonia in this case, almost impossible. Many of the RRB are historically viewed as intrinsic to ASD due to their early onset and consistency, but their striking similarity to catatonic symptoms and response to treatments like ECT challenge this assumption. Follow-up studies, especially the shared response to similar treatment modalities, do not support appropriate separation, especially when taken with the rest of the factors studied and similarly the extensive neurobiological overlap. Although this might be less specific, the research in this area is in its infancy. Family studies in this area appear to be lacking. Table 6 summarizes the results of applying the Robins and Guze[90] validity criteria to ASD in relation to catatonia.

Table 6 Applying Robins and Guze validity criteria to autism spectrum disorder in relation to catatonia[90].

Robins and Guze factors[90]	Criteria satisfaction
Clinical description	Several identical features between catatonia and ASD
Exclusion of other disorders	It is challenging to exclude and differentiate both syndromes from each other based on criteria
Follow up studies	Good response to similar modalities of treatment, such as lorazepam and ECT; ASD-related catatonia may be more chronic than catatonia associated with mood, psychotic, and systemic medical disorders
Laboratory studies	This area is in its infancy. However, a significant report shows an overlap in neurobiology
Family studies	No data available

ASD: Autism spectrum disorder; ECT: Electroconvulsive therapy.

Counterarguments

Advocates of RRB as core ASD features emphasize their consistent emergence in infancy, distinguishing them from the typically acute or episodic onset of catatonia. Yet chronic catatonia, though understudied, is documented in developmental disorders[12], and its occurrence in ASD may obscure these onset differences. They contend that functional distinctions, such as the adaptive role of RRB vs the purposelessness of catatonia, could reflect severity rather than separate etiologies, with severe RRB mirroring catatonia due to shared underlying mechanisms. Although neurobiological overlaps (e.g., SHANK3 mutations, GABA-A dysfunction) lack specificity, their significance grows when aligned with clinical and therapeutic similarities, and treatment response variability might arise from phenotypic diversity rather than distinct conditions. These counterarguments underscore the need for robust empirical research, including longitudinal studies tracking RRB and catatonia onset and randomized trials of catatonia-specific treatments, to unravel this complexity.

IMPLICATIONS AND LIMITATIONS

Feasibility and safety of clinical applications

Proposing catatonia treatments like lorazepam and ECT for ASD raises questions of feasibility and safety. While small case studies report efficacy, large-scale clinical trials are absent, and risks (e.g., sedation with lorazepam, cognitive effects of ECT) remain unquantified in ASD populations. Ethical considerations, particularly for pediatric patients, further complicate adoption. Randomized controlled trials are essential to assess efficacy, tolerability, and long-term outcomes.

Reclassification

If RRB were reframed as catatonic features, clinicians might prioritize benzodiazepines or ECT earlier, even for stable symptoms, reducing distress. Current approaches flag catatonia only with symptom changes, leaving chronic cases unaddressed.

Limitations and future recommendations

While the extensive overlap between ASD and catatonia creates a compelling argument and catalyst for paradigm evolution in neuropsychiatry, this potential assignment remains provisional. It requires validation and more support based on genomic, larger-scale imaging correlates and rigorous electrophysiological studies. Several reports describe the efficacy of options for treating catatonia, like lorazepam and ECT. However, larger studies and protocols for these populations are needed to establish the safety and effectiveness of these treatments for patients with ASD.

Future multimodal studies that combine functional genomics with advanced neuroimaging modalities to map shared neural circuit abnormalities are needed. In addition, multicenter randomized controlled trials to evaluate GABAergic agents under strict phenotypic stratification, incorporating biomarkers and response to biological treatments, should be considered for treatment response predictors.

CONCLUSION

There is considerable overlap in phenomenology, neurobiology, response to the same modalities of treatment, and increased predisposition and frequency of catatonia in patients with ASD. Evidence supporting the assignment of these overlapping presentations as core features of ASD is weak, and the distinct comorbidity of catatonia, and ASD seems to be a more compelling concept. Several approaches for distinguishing between the two clinical presentations focused on identifying a change in the severity or pattern of previous symptoms to suggest catatonia. While the authors agree with this approach, it leaves the assignment of cases with no changes in their chronic symptom pattern or severity without a clear answer. Answering this question significantly impacts clinical care and future studies, as it might provide treatment options for many of the RRB in ASD not previously considered for treatment because of their chronicity and conceptualization as an intrinsic feature of ASD. Future research should include randomized trials testing lorazepam and ECT in ASD patients with chronic RRB, alongside longitudinal studies to track symptom evolution and refine diagnostic boundaries. Reclassifying these symptoms could not only enhance diagnostic precision but also unlock targeted interventions, improving the quality of life for a significant subset of ASD individuals.