Exploring neuropsychiatric and behavioral symptoms, and social cognitive deficits in the differential diagnosis of behavioral variant of frontotemporal dementia and primary psychiatric A systematic literature review

Authors: Femke G. van Dijk, Linde Assendelft, Esther van den Berg, Lize C. Jiskoot

Abstract

The clinical overlap between behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) often results in delayed and incorrect diagnoses. We performed a literature review of 16 studies to evaluate how neuropsychiatric, behavioral, and social cognitive symptoms can aid in distinguishing bvFTD from PPD during early clinical assessment. Our study revealed differences in symptom profile and trajectory in the two diseases. Apathy, disinhibition, and compulsions were more likely to progress in bvFTD, while often remaining stable or improving in PPD. Changes in eating behavior and inappropriate social conduct, and emotion recognition, socioemotional sensitivity, and theory‐of‐mind impairments were more severe in bvFTD than in PPD. Although differential diagnosis can be challenging, studying the profile and progression of neuropsychiatric, behavioral, and social cognitive symptoms in bvFTD and PDD offers valuable diagnostic clues. Implementing structured tools and targeted assessments may improve differential diagnosis, ultimately guiding more appropriate treatment strategies.

INTRODUCTION

Behavioral variant frontotemporal dementia (bvFTD) represents the most prevalent clinical manifestation within the frontotemporal lobar degeneration (FTLD) spectrum. ^1^ bvFTD is primarily marked by early and insidious alterations in personality, behavior, and social conduct, symptoms closely linked to atrophy in the frontal and/or anterior temporal lobes. ^2^ , ^3^ Cognitive decline usually emerges later in the disease, alternatively is overshadowed by behavioral disturbances in the early stages. ^4^ , ^5^ Personality and behavioral changes include disinhibition, social inappropriateness, loss of empathy and sympathy, change of humor, obsessions/compulsions, and hyperorality. ^3^ Mood disturbances include apathy, euphoria, and irritability. ^2^ With respect to cognition, deficits in integrating social contextual information are frequently reported ^6^ and are proposed to underly problems in recognizing emotion in facial expressions, ^7^ understanding figurative speech, ^8^ and theory of mind. ^9^ One of the reasons that differential diagnosis is difficult, is that these behavioral, mood, and cognitive symptoms, especially in the early stages of bvFTD, frequently resemble those seen in primary psychiatric disorders (PPD). Among these PPD are major depressive disorder, bipolar disorder, schizophrenia, obsessive–compulsive disorder, autism spectrum disorder, and personality disorders that are often being confused with bvFTD. The overlap between bvFTD and certain PPDs may arise from shared behavioral features and involvement of similar brain regions. For instance, apathy and disinhibition in bvFTD can resemble symptoms of depression or bipolar disorder, while social withdrawal and reduced empathy may mimic autism spectrum disorder or schizophrenia. ^10^ , ^11^ , ^12^ , ^13^

Determining the underlying cause of personality, behavioral, and social cognitive decline later in life poses a significant clinical challenge, leading to diagnostic delay and misdiagnosis. ^14^ , ^15^ As a result of its pathological heterogeneity, there are currently no reliable, specific, and established biomarkers available for bvFTD. ^16^

Possible bvFTD is a purely clinical diagnosis, requiring the presence of three out of six features. ^2^ Complicating the differential diagnosis between possible bvFTD and PPD is that five of the six core diagnostic criteria are based on behavioral symptoms that largely overlap between disorders. Moreover, while the current diagnostic criteria are considered sensitive for probable/definite bvFTD (i.e., confirmed diagnosis through imaging and histopathology), ^2^ their specificity can be markedly low, dropping to almost 27% when biomarker evidence of neurodegeneration is not available. ^17^ Although neuroimaging can assist in distinguishing bvFTD from PPD, its diagnostic utility remains limited. Structural magnetic resonance imaging (MRI) often lacks sensitivity in early disease stages, and ^18^F‐FDG‐PET may not provide sufficient specificity to confidently differentiate bvFTD from PPD. ^18^ On average, accurate bvFTD diagnosis is achieved 5–6 years after symptom onset. ^14^ , ^15^ , ^19^ , ^20^ , ^21^ Even upon follow‐up, the clinical diagnosis is often changed into another type of dementia, neurological disease, or PPD. ^12^ , ^22^ More than 20% of patients with bvFTD are initially diagnosed with an PPD. ^23^ However, more recent findings indicate that the amount of patients misdiagnosed is approximately 13%, a rate considerably lower than previously reported. ^24^ Compounding the diagnostic complexity, comorbid psychiatric symptoms are frequently observed in patients with bvFTD. ^12^ , ^13^ , ^14^ , ^15^ However, standard cognitive and functional assessments commonly used in dementia diagnosis often fail to detect the behavioral and emotional disturbances characteristic of bvFTD, ^25^ even within specialized clinical settings. This limitation underscores the importance of incorporating structured behavioral interviews into the diagnostic process. ^26^ Several authors have emphasized the necessity of assessing social cognition, advocating for the inclusion of at least one dedicated test to capture these deficits. ^27^ , ^28^ , ^29^ While several strategies have shown promise in enhancing diagnostic accuracy in smaller studies, such as the structured use of clinical scales, ^30^ neuropsychiatric evaluations, ^19^ and comprehensive social cognitive batteries, ^31^ a standardized approach has yet to be established.

Early and accurate diagnosis of bvFTD should be considered a priority as caregivers report a high degree of negative impact of the neuropsychiatric, behavioral, and/or social cognitive symptoms on their quality of life. ^22^ , ^23^ Additionally, misdiagnosis may have implications for medication and symptom management. ^20^ This review addresses these diagnostic challenges by evaluating the scientific literature to provide an overview of current findings on the differential diagnosis of bvFTD and PPD. To do so, we focused on two key domains that contribute to diagnostic uncertainty in early stages of neuropsychiatric/behavioral symptoms and social cognition. These domains are central to the diagnostic criteria for bvFTD and have been shown to overlap considerably with various PPD. A better understanding of the patterns and progression of these features may help clinicians detect bvFTD at an earlier stage, especially in cases where biomarker support is lacking and diagnosis relies primarily on clinical assessment.

MATERIALS AND METHODS

In collaboration with the Erasmus MC University Medical Centre Medical Library, the appropriate MeSH and entry terms for this study were identified. A literature search was performed in MedLine ALL (Ovid) and Embase for peer‐reviewed published articles written in English covering the period from inception to April 2025 (see Appendix for an overview of the search terms and Figure 1 for the Preferred Reporting Items for Systematic Reviews and Meta‐analyses [PRISMA] flowchart). The search contained terms for (1) frontotemporal dementia, (2) psychiatric disorders, (3) diagnostic keywords, and (4) neuropsychiatric, behavioral, and social cognitive symptoms. Importantly, the latter category consisted of a detailed list of individual symptoms and constructs (e.g., apathy, disinhibition, empathy, emotion recognition) to ensure comprehensive coverage of relevant literature. Reviews, editorials, letters, conference abstracts, books (including dissertations) or book chapters, case reports, and animal studies were excluded from the search. A total of 233 articles were identified and imported into EndNote. Title, abstract, and full text were manually screened for inclusion. Articles were included if they reported any association, overlap, or difference in terms of clinical presentation between bvFTD and PPD. Lastly, reference lists of selected articles were screened for additional articles. The described methods in this review are based on the PRISMA Checklist″ ^32^ and the Prisma‐S extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. ^33^

Data extraction

The following data were extracted from the authorship, year of publication, country where the study took place, study aims, study design, characteristics of the population, clinical assessment tools, and main results. Additionally, we noted which methods were utilized to assess neuropsychiatric and behavioral and social cognitive symptoms (e.g., standardized questionnaires, report inventories, neuropsychological tests).

Ethics statement

This study was performed in accordance with the Declaration of Helsinki for medical research involving human subjects and followed PRISMA guidelines for systematic reviews and meta‐analyses. ^32^

RESULTS

General characteristics

Sixteen studies were considered eligible for inclusion in the current literature review, see Table 1 for an overview of study characteristics and main findings. Sample sizes ranged between 29 and 89 patients, ranging between 16 and 63 patients diagnosed with bvFTD and between 11 and 47 patients diagnosed with PPD. Disease duration was reported in 10 of the included studies. In studies using median and interquartile range, both bvFTD and PPD symptom duration ranged from 3 to 5 years. ^30^ , ^34^ , ^35^ , ^36^ In the other studies, means of 2.4–6.5 years of bvFTD disease duration and 3.2–7 years of PPD duration were reported. ^37^ , ^38^ , ^39^ , ^40^ Additionally, two studies showed mean PPD symptom duration exceeding 20 years. ^41^ , ^42^ Notably, several studies reported data from the Social Brain Project ^34^ , ^43^ and its preceding late‐onset frontal lobe study. ^30^ , ^35^ , ^36^ , ^37^ , ^44^ , ^45^ All but one ^37^ of the included studies were prospective studies. Four of the 16 studies had a longitudinal design. ^35^ , ^36^ , ^43^ , ^45^ The included studies were published between 2000 and 2025. Most studies applied the revised Rascovsky et al. ^2^ criteria for bvFTD. Three earlier studies ^30^ , ^31^ , ^44^ used alternative criteria and revered to those by Rascovsky et al., ^46^ Neary et al., ^4^ or Brun et al. ^47^ For two studies, ^37^ , ^48^ the applied diagnostic criteria were not specified. Across studies, diagnoses were primarily based on clinical evaluation, with limited use of biomarker or pathological confirmation. Studies described the following PDD: major depressive disorder (n = 10), bipolar disorder (n = 11), personality disorder (n = 8), autism spectrum disorder (n = 7), schizophrenia (n = 6), and obsessive‐compulsive disorder (n = 6). Several cohorts also included healthy controls (n = 6) and other types of dementia (n = 7), including Alzheimer's dementia, progressive supranuclear palsy, corticobasal syndrome, semantic variant primary progressive aphasia, and vascular dementia.

Neuropsychiatric and behavioral symptoms

Nine studies compared neuropsychiatric and behavioral symptoms through the use of clinical assessment scales. ^29^ , ^36^ , ^43^ , ^48^ The Frontotemporal Dementia Rating Scale (FRS) is used by clinicians to monitor disease severity in bvFTD by reviewing the presence of functional dependence and behavioral symptoms. ^49^ One of the included studies conducted a 2‐year longitudinal follow‐up and found a decline in daily functioning and behavioral symptoms in patients with bvFTD, whereas these symptoms remained stable in patients with PPD. ^43^ Other clinical assessment tools that can potentially aid the distinction between bvFTD and PPD are the Cambridge Behavioral Inventory‐Revised (CBI‐R) ^50^ and Frontal Behavioral Inventory (FBI). ^51^ The CBI‐R is an informant‐based questionnaire assessing cognitive, behavioral, and affective symptoms along with activities of daily living, whereas the FBI is mainly used to rate the severity of a range of behaviors distinct to bvFTD. ^51^ Two studies used these instruments in the differentiation between bvFTD and PPD. ^36^ , ^43^ Both reported that the frequency and severity of behavioral symptoms worsened in bvFTD in the course of 2 years, while in patients with PPD no change and even a slight improvement was found. Additionally, Kertesz et al. ^38^ showed that patients with bvFTD scored significantly higher on certain negative (i.e., apathy, aspontaneity, inflexibility, disorganization) and positive sub‐items (i.e., irritability, jocularity, judgment, restlessness, aggression, hyperorality, personal neglect) of the FBI than those with major depressive disorder. Throughout the bvFTD disease course negative symptoms increased while positive symptoms did not. In PPD, the opposite was seen. ^43^ However, Krishnadas et al. ^37^ described that patients with bvFTD could not be distinguished from other conditions based on overall caregiver‐observed behavior (using the CBI‐R), but when looking at changes in eating habits, they did find significantly higher scores for patients with bvFTD than for those with PPD. The Stereotypy Rating Inventory (SRI) is informant‐based tool, used to identify stereotypy in bvFTD. ^52^ One of the three studies using the SRI found stereotypies to be more present in bvFTD than PPD populations. ^30^ In the second study, ^36^ trajectories of stereotypic and compulsive behaviors did not change after 2 years nor differ between patients with bvFTD and PPD. In the third study, ^43^ these types of behaviors increased over time in bvFTD, while stabilizing in PPD.

One of the nine included studies ^48^ examined whether social behaviors seen during the diagnostic phase could differentiate bvFTD versus PPD, utilizing the Interpersonal Measure of Psychopathy (IM‐P). Results showed an ‘unusual calmness’ in patients with bvFTD during the clinical exam in comparison to those with PPD. They were also more likely to cross personal and professional boundaries or interrupt the assessment by engaging with the examiner. In the past few years, several tools have been developed to improve the diagnostic process of bvFTD. One of these is the Frontotemporal Dementia versus Primary Psychiatric Disorder (FTD vs. PPD) Checklist, a questionnaire focusing on key clinical differentiating factors. ^44^ Patients with probable bvFTD scored significantly higher on the checklist than those with PPD. Additionally, a score of 11 or above was suggested to be indicative of bvFTD, while a score of 8 or lower signified PPD. Another recently developed behavioral inventory, DAPHNE, was designed to differentiate bvFTD from other conditions. ^41^ DAPHNE‐6 functions as a screener, whereas DAPHNE‐40 is meant for diagnostic purposes. Those with bvFTD scored significantly higher on both versions of the inventory than patients with bipolar disorder. Moreover, a score of four or above was suggestive for bvFTD when using DAPHNE‐6, while a score of fifteen or higher on DAPHNE‐40 distinguished bvFTD from bipolar disorder. Lastly, Jiskoot et al. ^39^ developed an extended assessment tool designed to supplement the Neuropsychiatric Inventory (NPI) with eight additional items relevant to bvFTD (FTD Module). While patients with PPD exhibited the most severe neuropsychiatric and behavioral disturbances on both the NPI and NPI with FTD Module, the addition of the latter significantly improved differentiation between diagnostic groups. The model, including the FTD Module, achieved correct classification rates of 82.9% for bvFTD and 83.3% for PPD.

Social cognition

Social cognition encompasses the mental processes involved in understanding and navigating social interactions, including interpreting behaviors, emotions, and others’ intentions. ^53^ It includes both lower‐level skills such as emotion recognition, and higher‐order abilities such as theory of mind, empathy, and moral reasoning. ^54^ These capacities are considered crucial for maintaining appropriate social behavior and navigating interpersonal relationships. ^53^ , ^55^ In patients with bvFTD, impairments across multiple social cognitive domains have been reported consistently. ^56^ From the 16 included studies, 9 examined social cognition in bvFTD and PPD. Emotion recognition was most often investigated (n = 4). The evaluation of emotion recognition relies mostly on static stimuli, requiring patients to label the emotion expressed on faces (e.g., Ekman 60‐Faces Test and Mini‐Social Cognition and Emotional Assessment [Mini‐SEA]). Patients with bvFTD show impaired facial expression recognition compared to patients with PPD. ^34^ , ^35^ , ^36^ , ^43^ , ^45^ As these studies used the Ekman 60‐Faces Test, this psychometric test appears to be a robust discriminator between bvFTD and a wide range of PPD. Emotion recognition was found to worsen over time in two studies, ^34^ , ^35^ while performance remained stable in PPD. ^36^ , ^43^ Two studies focusing on bvFTD and bipolar disorder found similar low performances between the two groups on emotion recognition. ^42^ , ^57^ Moreover, two studies targeted bvFTD and major depressive disorder specifically. ^31^ , ^55^ Bertoux et al. ^31^ further showed that the Mini‐SEA may have an important discriminatory value. They found that those with bvFTD scored significantly lower than patients with major depressive disorder, with minimal overlap between groups. Chiu et al. ^40^ used an emotion intensity rating task, in which patients were presented with faces expressing the six basic emotions at different intensity levels. Contrary to patients with bvFTD, those with major depressive disorder were able to discriminate between the expressed emotions at the same valence. Patients with bvFTD also experienced more difficulty in perceiving the intensity of the emotions. Notably, patients with bvFTD tended to perceive negative emotions as less intense, whereas those with major depressive disorder showed heightened sensitivity to these emotions.

Fieldhouse et al. ^43^ also assessed socioemotional sensitivity (e.g., the ability to understand social cues and show appropriate behavior) by using a brief screening tool, the Revised Self‐Monitoring Scale (RSMS). Caregivers of patients with bvFTD reported a decrease in socioemotional sensitivity, while patients did not mention any change themselves. ^43^ In contrast, in PPD neither caregivers nor patients reported alterations in socioemotional sensitivity. This discrepancy in bvFTD may reflect anosognosia, which is less typically seen in PPD ^58^ and might help distinguish the two groups further. Delving deeper into the topic of social‐emotion, emotional susceptibility refers to the tendency to feel upset, helpless, insecure, or vulnerable in response to emotionally charged situations. ^59^ Change in this subdomain of social cognition did not differ between bvFTD and PPD and was stable over time. ^35^

Two of the nine included studies reported that theory of mind capabilities (i.e., the ability to attribute thoughts and feelings to oneself and others) were similar between patients with bvFTD and those with PPD. ^35^ , ^36^ As both diseases progressed, performance increased equally on the Faux Pas test. ^36^ However, two studies specifically focused on bipolar disorder ^42^ , ^57^ found that both cognitive and affective components of theory of mind (assessed with the Reading the Mind in the Eyes Test) were significantly more impaired in bvFTD than in PPD.

DISCUSSION

This literature review aimed to explore how neuropsychiatric, behavioral, and social cognitive symptoms can help distinguish bvFTD from PPD. Across the 16 included studies in this review, several key findings emerged that highlight the potential value of these clinical features in differential diagnosis. To summarize, while bvFTD and PPD may overlap in neuropsychiatric, behavioral, and social cognition symptoms, there are several important differences in how these symptoms present in the diagnostic phase and how they progress over time.

In bvFTD, neuropsychiatric and behavioral changes such as apathy, disinhibition, and compulsivity tend to increase in severity over time and are often accompanied by daily function decline. ^36^ , ^43^ In contrast, patients with PPD frequently remain stable or show partial improvement. ^43^ This difference in symptom trajectory can serve as an important diagnostic indicator, especially when observed over multiple consultations. Moreover, features like unusual calmness and boundary‐crossing behavior during clinical assessment may further support the suspicion of bvFTD. ^37^ , ^48^ However, inconsistent findings regarding stereotypic behavior underline the need for careful individual assessment and not overreliance on a single symptom. ^30^ , ^36^ The clinical assessment tools included in this review may provide valuable diagnostic support in such cases. Recently developed instruments such as the FTD versus PPD Checklist, DAPHNE inventories, and NPI with FTD Module showed good discriminative accuracy and might offer a structured approach to symptom evaluation. ^39^ , ^41^ , ^44^ These clinical assessment tools can help standardize diagnostic procedures and may be particularly useful in psychiatric settings where bvFTD may not always be considered immediately. Collectively, these findings emphasize the importance of not only identifying specific neuropsychiatric and behavioral symptoms and how they may show different cluster patterns but also considering their change during disease progression in bvFTD and PPD. Structured tools that incorporate such symptom profiles offer a promising approach to enhance the accuracy and reliability of bvFTD diagnosis in the absence of biomarker evidence.

In addition to neuropsychiatric and behavioral symptoms, impairments in social cognition are a core feature of bvFTD and could support the differentiation from PPD. The results of this review indicate that social cognitive impairments are more severe and more consistent in patients with bvFTD than in PPD. Emotion recognition is frequently impaired in bvFTD and tends to worsen over time ^34^ , ^35^ , ^36^ , ^43^ , ^45^ while patients with PPD generally maintain their ability to recognize emotions and in some cases, even show heightened sensitivity to emotional intensity. ^40^ This contrast may reflect fundamental differences in underlying neuropathology ^40^ , ^44^ and supports the use of emotion recognition tasks as part of the clinical work‐up. While theory of mind outcomes were mixed across studies, findings from comparisons between bvFTD and bipolar disorder suggest that both cognitive and affective components may be more severely impaired in bvFTD than in PPD. ^42^ , ^57^ Other studies found no differences in Faux Pas test performance between bvFTD and PPD, with both groups showing similar improvements over time. ^35^ , ^36^ Taken together, this review highlights that impairments in emotion recognition and socioemotional functioning, in combination with behavioral observations and informant input, may offer clinically meaningful information and that incorporating them in the diagnostic process could help differentiate bvFTD from PPD that may present similarly at onset but follow different courses over time. Across studies, differences between bvFTD and PPD were generally more pronounced in later disease stages, when behavioral disinhibition, apathy, or loss of empathy became more evident. ^34^ , ^35^ , ^36^ , ^43^ However, some novel assessment tools also demonstrated discriminative value earlier in the disease course. For example, the DAPHNE and the FTD versus PPD Checklist were able to capture subtle behavioral changes even in patients with only mild functional impairment, ^36^ , ^52^ while measures of emotion recognition (e.g., Ekman 60‐Faces Test) revealed social cognitive deficits in mild bvFTD that were not observed in PPD. ^33^ , ^34^ These findings suggest that both behavioral rating scales and social cognitive tests may contribute to differentiation at early stages of symptom development.

The findings from this review suggest that clinical differentiation between bvFTD and PPD may benefit significantly from a greater emphasis on neuropsychiatric, behavioral, and social cognitive symptom patterns. On a broader level, these results underscore the need to move beyond symptom presence alone and instead focus on symptom dynamics and context. Rather than relying solely on general psychiatric diagnostic criteria or standard cognitive testing, clinicians may improve diagnostic accuracy by evaluating how specific symptoms cluster and change over time. For instance, a flat affect or disinhibition in itself may not be diagnosis‐specific, but its progression, co‐occurrence with other behavioral changes, or lack of disease insight could signal a neurodegenerative rather than primary psychiatric origin. It is especially relevant in settings where biomarker testing is unavailable, as can be the case in psychiatric or primary care contexts. These findings also point toward the potential utility of structured behavioral and social cognitive tools in early differential diagnosis. The use of tailored checklists and assessments could support clinicians in identifying patients who need further cognitive and neurological evaluation. Integration of these tools into routine diagnostic procedures could improve diagnostic accuracy, reduce misclassification, and ultimately lead to more appropriate and early care for patients and support for those around them.

First limitation of this review is that most of the included studies relied on standardized psychometric tools to assess neuropsychiatric and behavioral symptoms and social cognition. Although these instruments support objectivity and consistency across studies, other clinically relevant methods (e.g., history taking, informant‐based interviews) were not structurally evaluated to such an extent. These approaches are often central to diagnostic decision‐making and may provide additional insights that standardized tools do not capture. In addition, studies focusing on neuroimaging and/or biomarker data, without any mention of social cognition or behavioral change in bvFTD and PPD, were excluded from this review as our review focused on front‐line diagnostic methods that are more likely to be available in everyday care settings. Additionally, most studies grouped different PPDs and neurodevelopmental disorders into one group. Only a small number of studies provided direct comparisons between bvFTD and specific psychiatric diagnoses such as bipolar disorder or major depressive disorder. This limits the level of diagnostic specificity and reduces the ability to draw conclusions about how bvFTD differs from each PPD separately. Nevertheless, some differences in behavioral and social cognitive symptoms were also observed in studies comparing bvFTD to individual disorders, suggesting that certain symptom patterns may be relatively consistent across diagnostic contexts. However, as noted by Fieldhouse et al., ^34^ heterogeneity within PPD cohorts may obscure these findings, since the severity and nature of social cognitive impairments vary substantially across disorders. For example, emotion recognition deficits in major depressive disorder often reflect mood‐congruent biases, ^40^ whereas individuals with autism spectrum disorder may show reduced fixation on the eyes when processing emotions. ^60^ Therefore, findings should be interpreted with caution, and future research should examine disorder‐specific profiles, as the extent of symptomatic overlap with bvFTD is likely to vary by diagnosis. The longitudinal studies in this review followed patients for a maximum period of two years. This timeframe remains limited in capturing the full course of the disease process. On average, an accurate diagnosis of bvFTD is made 5–6 years after symptom onset, ^13^ , ^14^ , ^17^ , ^18^ , ^19^ , ^21^ suggesting that symptom development continues and possibly changes beyond this 2‐year follow‐up period. For instance, Fieldhouse et al. ^43^ reported that although 71.9% of patients retained the same diagnosis after 2 years, 18% moved from a postponed to a definitive diagnosis, and 3.4% switched from possible bvFTD to PPD. These findings underscore that even within a 2‐year window, diagnostic shifts can occur, highlighting the limitations of short‐term follow‐up when assessing long‐term symptom evolution. In addition, there is a potential risk of diagnostic circularity. Behavioral and social cognitive symptoms are often part of the clinical criteria used to define bvFTD. When the same symptoms are then studied as possible differentiators, this may lead to biased findings that reinforce the original diagnosis. While some studies attempted to mitigate this by including longitudinal data, ^35^ , ^36^ , ^43^ , ^45^ future research may incorporate prospective validation or biomarker‐supported classification to help ensure that observed differences in symptom profiles reflect true diagnostic distinctions rather than methodological errors. It should also be acknowledged that diagnostic certainty varied across the included studies. While most used the Rascovsky et al. ^2^ criteria, some applied earlier frameworks or did not specify their diagnostic approach, and few included biomarker confirmation. As a result, part of the observed overlap in behavioral and social cognitive symptoms may reflect diagnostic uncertainty rather than true clinical similarity. Lastly, several included studies based results on relatively small samples and were from the same cohorts from similar geographical areas. Consequently, while these studies provide valuable insights, studies might have been underpowered and findings may reflect analyses from overlapping datasets rather than multiple independent cohorts. Future research should aim for larger, more diverse, and internationally representative samples. Standardizing diagnostic tools and assessment batteries across centers may also help improve comparability between studies and facilitate clinical implementation.

CONFLICT OF INTEREST STATEMENT

The authors have no competing interests to declare that are relevant to the content of this article. Author disclosures are available in the Supporting Information.

ETHICAL APPROVAL AND INFORMED CONSENT

This study was performed in accordance with the declaration of Helsinki for medical research involving human subjects and followed PRISMA guidelines for systematic reviews and meta‐analyses.

Supporting information