Autism Spectrum Disorder and Mental Health Comorbidity: Anxiety, Depression, and OCD — Prevalence, Neurobiology, and Adapted Interventions

Psychiatric comorbidity in autism spectrum disorder (ASD) is not an occasional clinical complication — it is the normative experience. Large-scale epidemiological studies consistently demonstrate that 70–80% of autistic individuals meet criteria for at least one co-occurring psychiatric condition, and approximately 40% meet criteria for two or more. Anxiety disorders, depressive disorders, and obsessive-compulsive disorder (OCD) are among the most prevalent and clinically significant of these comorbidities, yet they remain systematically underdiagnosed and undertreated in the autistic population.

The clinical challenge is substantial. The core features of ASD — restricted and repetitive behaviors, social communication differences, sensory sensitivities, and alexithymia — can mask, mimic, or fundamentally alter the presentation of internalizing disorders. A clinician who applies standard diagnostic algorithms without accounting for the autistic phenotype risks both false positives (misinterpreting autistic traits as psychiatric symptoms) and false negatives (failing to recognize genuine psychiatric distress expressed through atypical channels).

This article provides a detailed clinical review of the intersection between ASD and three of its most common psychiatric comorbidities: anxiety disorders, major depressive disorder (MDD), and OCD. We examine bidirectional prevalence, shared and distinct neurobiological mechanisms, the ways comorbidity transforms clinical presentation, evidence for adapted interventions, and the prognostic implications of co-occurring conditions. The goal is to equip clinicians, researchers, and informed readers with the depth of understanding necessary to recognize and address these complex clinical presentations.

Anxiety Disorders in ASD

Meta-analytic evidence places the prevalence of clinically significant anxiety in autistic individuals at approximately 42% (van Steensel et al., 2011), with estimates ranging from 27% to 54% across studies depending on methodology, age group, and diagnostic approach. Specific anxiety disorders show varying prevalence: social anxiety disorder affects an estimated 17–30% of autistic individuals, generalized anxiety disorder (GAD) 15–28%, specific phobias 25–44%, and separation anxiety 9–21%. These rates are roughly 3–5 times higher than in the general population.

Looking in the reverse direction — the prevalence of ASD traits among individuals diagnosed with anxiety disorders — data are sparser but revealing. Studies of adults in anxiety disorder clinics have found that 10–20% screen positive for elevated autistic traits, and approximately 3–6% may meet full diagnostic criteria for ASD. In pediatric anxiety specialty clinics, rates of undiagnosed ASD have been reported as high as 10–14%, suggesting that anxiety clinics may serve as an important point of ASD case identification.

Depressive Disorders in ASD

Meta-analyses estimate the lifetime prevalence of major depressive disorder in autistic adults at approximately 37%, with current (point) prevalence estimates around 20–26% (Hudson et al., 2019). These figures represent a roughly 4-fold elevation over general population lifetime rates of approximately 10–15%. Depression appears to increase markedly from adolescence into adulthood, with some longitudinal studies suggesting that cumulative exposure to social isolation, employment difficulties, and minority stress contributes to a worsening trajectory over time.

In the reverse direction, studies examining ASD prevalence among individuals with treatment-resistant depression have found elevated rates of autistic traits. An estimated 5–10% of individuals presenting to mood disorder clinics with chronic or refractory depression may have unrecognized ASD, though rigorous epidemiological data remain limited. This finding has particular clinical significance because unrecognized ASD may partly explain treatment resistance.

OCD in ASD

The relationship between ASD and OCD is both the most clinically confounding and the most neurobiologically informative of the three comorbidities considered here. Meta-analytic data suggest that 17–25% of autistic individuals meet diagnostic criteria for OCD, compared to approximately 2–3% in the general population (Meier et al., 2015). Conversely, studies of OCD clinic populations have found that approximately 6–10% of individuals with OCD may have comorbid ASD, and as many as 20–25% show elevated autistic traits on standardized screening measures without meeting full diagnostic criteria.

These bidirectional prevalence figures underscore a critical clinical point: when any one of these conditions is identified, systematic screening for the others is not optional — it is essential for competent clinical practice.

Overlapping Neural Circuitry

ASD, anxiety, depression, and OCD share involvement of several key neural systems, which helps explain their frequent co-occurrence while also complicating efforts to disentangle them clinically.

The amygdala-prefrontal circuit is implicated across all four conditions. In ASD, functional neuroimaging studies consistently demonstrate atypical amygdala reactivity to social stimuli, with evidence of early-life amygdala hyperactivation followed by possible habituation failure. This same circuit shows hyperactivation in anxiety disorders and altered functional connectivity in depression. In OCD, the cortico-striato-thalamo-cortical (CSTC) loop — which includes prefrontal regulatory regions — shows characteristic hyperactivity. The overlap in prefrontal-limbic dysregulation provides a plausible neural substrate for the co-occurrence of these conditions.

Serotonergic and GABAergic Systems

Serotonin (5-HT) system dysfunction is documented in all four conditions. In ASD, altered serotonin synthesis capacity has been demonstrated using PET imaging, and approximately 30% of autistic individuals show elevated whole-blood serotonin levels (hyperserotonemia). Serotonergic dysfunction is the primary pharmacological target in both depression (via SSRIs/SNRIs) and OCD (via high-dose SSRIs and clomipramine). GABAergic inhibitory neurotransmission, which modulates anxiety circuits, shows evidence of disruption in ASD, with multiple postmortem and genetic studies identifying reduced GABA receptor expression in autistic brains. GABA deficits may partly explain the heightened sensory reactivity and anxiety vulnerability observed in ASD.

Intolerance of Uncertainty

A construct receiving increasing attention as a transdiagnostic mechanism is intolerance of uncertainty (IU). IU is elevated in ASD, GAD, OCD, and depression, and emerging research suggests it may function as a cognitive hub connecting autistic information-processing differences with vulnerability to internalizing psychopathology. Studies by Boulter et al. (2014) and Jenkinson et al. (2020) demonstrated that IU significantly mediates the relationship between autistic traits and anxiety symptoms, even after controlling for other cognitive variables. This suggests that interventions targeting IU may be particularly efficient for autistic individuals with comorbid anxiety.

HPA Axis Dysregulation

Hypothalamic-pituitary-adrenal (HPA) axis function is altered in ASD, with atypical cortisol diurnal profiles, blunted cortisol reactivity to social stressors, and elevated cortisol in response to sensory stressors. Depression and anxiety are both associated with HPA axis dysregulation, though the specific patterns differ (hypercortisolism in melancholic depression, blunted reactivity in atypical depression and chronic stress). The interaction of ASD-related stress system differences with environmentally mediated HPA activation from social adversity may create a neurobiological "double hit" that increases vulnerability to mood and anxiety disorders.

Genetic Overlap

Genome-wide association studies (GWAS) and family studies provide evidence of shared genetic architecture. A large Danish register-based study (Meier et al., 2015) demonstrated significantly elevated rates of OCD in first-degree relatives of autistic individuals, and vice versa, suggesting shared genetic liability. Polygenic risk scores for ASD show modest but significant correlations with genetic risk for anxiety and depression. Candidate gene studies have identified overlap in genes involved in synaptic formation (e.g., SHANK3, NRXN1), serotonin transport (SLC6A4), and oxytocin receptor function (OXTR).

Anxiety in Autistic Individuals: Atypical Presentations

Anxiety in autistic individuals frequently does not conform to the prototypical presentations described in DSM-5-TR for neurotypical populations. Several characteristic differences complicate diagnosis:

• Sensory-driven anxiety: Many autistic individuals experience intense anxiety triggered by sensory environments (noise, lighting, textures, crowds) that would not typically provoke anxiety in non-autistic individuals. This presentation does not map neatly onto any existing DSM-5-TR anxiety diagnosis but causes clinically significant distress and functional impairment.
• Change-related and transition anxiety: Anxiety triggered by routine disruption, unpredictability, or transitions between activities may resemble GAD but is more specifically linked to autistic need for predictability.
• Social anxiety versus social communication differences: Distinguishing social anxiety disorder from ASD-related social communication difficulties is one of the most challenging diagnostic differentials in clinical practice. Both produce social avoidance and distress in social situations, but the underlying mechanism differs: social anxiety involves fear of negative evaluation, while autistic social difficulty involves challenges with pragmatic language, nonverbal communication, and social cognition. Critically, these can co-occur — and frequently do.
• Alexithymia: Approximately 50% of autistic individuals have clinically significant alexithymia (difficulty identifying and describing emotions), compared to roughly 10% of the general population. This means that many autistic individuals cannot self-report anxiety in the way that standard diagnostic interviews expect, leading to underdiagnosis.

Depression: Masked by Autistic Features

Depressive episodes in autistic individuals may present with increased withdrawal (beyond baseline), intensification of restricted interests (used as coping mechanisms), increased sensory sensitivity, behavioral regression, increased rigidity, loss of previously acquired adaptive skills, or increased irritability and meltdowns rather than reported sadness. Standard depression screening instruments (PHQ-9, BDI-II) have limited validation in autistic populations and may miss atypical presentations while producing false positives from items that overlap with autistic traits (e.g., social withdrawal, sleep disturbance, concentration difficulties).

OCD Versus Autistic Repetitive Behaviors: The Critical Differential

Distinguishing OCD compulsions from autistic repetitive behaviors (restricted and repetitive behaviors, or RRBs) is arguably the single most difficult differential diagnostic question in this clinical domain. Key differentiating features include:

• Ego-dystonicity: Classic OCD compulsions are experienced as intrusive, unwanted, and distressing (ego-dystonic). Autistic RRBs are typically experienced as pleasurable, comforting, or regulatory (ego-syntonic).
• Motivating affect: OCD compulsions are driven by anxiety and a need to prevent feared outcomes. Autistic RRBs are often driven by sensory seeking, need for sameness, or intrinsic interest.
• Content: OCD obsessions frequently involve contamination, harm, symmetry, or taboo themes. Autistic special interests tend to involve systematizing, collecting, or deep engagement with specific topics.

However, this distinction is far less clear in practice than in textbooks. Autistic individuals can develop genuine OCD that co-occurs with their RRBs. Some repetitive behaviors may begin as ego-syntonic autistic routines and evolve into ego-dystonic compulsions. Alexithymia may prevent the autistic individual from clearly reporting the subjective experience that would allow differentiation. Clinicians must often rely on longitudinal observation, informant reports, and careful functional analysis rather than cross-sectional diagnostic interviews alone.

Vignette 1: Anxiety or Autism? A Missed Diagnosis

A 24-year-old woman presents to an anxiety disorders clinic after three failed trials of CBT for social anxiety disorder. She reports intense distress in social situations, avoidance of group settings, difficulty making friends, and chronic worry. She was diagnosed with social anxiety disorder at age 16. On detailed history, the clinician notes that her social difficulties predate any anxiety symptoms, beginning in early childhood. She describes not understanding social rules, taking figurative language literally, and feeling exhausted after social interaction — consistent with autistic social communication differences rather than (or in addition to) social anxiety. She also reports intense engagement with specific topics (botanical taxonomy), sensory sensitivity to fluorescent lighting, and a strong preference for routine. Standardized assessment (ADOS-2, ADI-R, self-report) confirms ASD diagnosis. Her previous CBT failures are recontextualized: the treatment targeted social anxiety cognitions that were not the primary driver of her social difficulties. An adapted intervention plan incorporating psychoeducation about autism, sensory accommodations, and modified CBT for genuine comorbid anxiety produces significant improvement.

Vignette 2: OCD, RRBs, or Both?

A 15-year-old boy with known ASD (diagnosed at age 7) is referred for increasing repetitive behavior. He has begun spending 2–3 hours daily arranging and rearranging his collection of model trains in a specific order. His parents report that he becomes extremely distressed if the arrangement is disrupted, sometimes resulting in meltdowns. Is this an intensification of a pre-existing autistic interest, or has OCD developed? On careful interview, the clinician discovers that the arranging behavior, previously enjoyable, has become associated with a belief that "something bad will happen" if the trains are not in the correct order. He reports intrusive mental images of his mother being hurt, which the arranging temporarily alleviates. He does not want to have these thoughts and feels trapped by the ritual. This presentation reflects genuine OCD superimposed on a pre-existing autistic interest: the content domain (trains, ordering) is consistent with his autistic profile, but the functional mechanism (intrusive thoughts, anxiety reduction, ego-dystonicity) indicates OCD. Treatment with adapted ERP (exposure and response prevention) alongside continuation of appropriate autistic accommodations is indicated.

Vignette 3: Autistic Burnout Misdiagnosed as Depression

A 32-year-old autistic man with a history of strong academic performance and stable employment presents with 6 months of progressive fatigue, loss of executive function skills, increased sensory sensitivity, withdrawal from previously enjoyed activities, and loss of previously acquired independent living skills. He was diagnosed with MDD and started on sertraline, with no response after 8 weeks at adequate dose. Review reveals that symptoms followed a period of prolonged workplace social demands, extended masking, and reduced access to restorative activities. This presentation is more consistent with autistic burnout — a phenomenon increasingly recognized in the literature (Raymaker et al., 2020) characterized by pervasive exhaustion, loss of skills, and reduced tolerance to stimuli — than with a primary depressive episode. Management involves environmental modification, reduction of masking demands, increased access to special interests and restorative solitude, and monitoring for co-occurring depression, which frequently accompanies burnout.

SSRIs: Different Responses in ASD

The pharmacological treatment of comorbid anxiety, depression, and OCD in autistic individuals is complicated by evidence that treatment response may differ significantly from non-autistic populations. The evidence base is limited, with few large randomized controlled trials specifically examining psychiatric medication efficacy in autistic adults.

For anxiety and depression, SSRIs remain the first-line pharmacological approach, but clinical experience and limited trial data suggest that autistic individuals may require lower starting doses and slower titration due to increased sensitivity to side effects, particularly activation, gastrointestinal disturbance, and behavioral agitation. A systematic review by Horder et al. (2018) found that evidence supporting SSRI use for anxiety and depression specifically in autistic adults is weak, with most data extrapolated from non-autistic populations. The pediatric evidence is somewhat stronger for fluoxetine and fluvoxamine, though effect sizes are modest.

For OCD in ASD, high-dose SSRIs (fluoxetine 40–80 mg, fluvoxamine 150–300 mg, sertraline 150–200 mg) remain the pharmacological standard, consistent with OCD treatment guidelines in general populations. However, the response rate may be lower: clinical observations suggest that approximately 30–40% of autistic individuals with OCD show meaningful improvement with SSRIs, compared to approximately 50–60% in non-autistic OCD populations, though head-to-head comparisons are lacking.

Adjunctive Strategies

When SSRIs are insufficient, augmentation strategies used in the general population — including low-dose antipsychotic augmentation (e.g., aripiprazole, risperidone) — are sometimes employed. However, autistic individuals may be at elevated risk for metabolic side effects and extrapyramidal symptoms. Buspirone has shown some promise for anxiety in ASD in small studies. N-acetylcysteine (NAC), a glutamate modulator, has been investigated for repetitive behaviors in ASD with mixed results. Memantine has shown preliminary promise for OCD symptoms in ASD through glutamatergic modulation.

Key Clinical Principles

• Start low, go slow — but do achieve therapeutic doses when tolerated
• Monitor for activation and behavioral side effects carefully
• Be prepared for atypical side effect profiles
• Distinguish medication-responsive psychiatric symptoms from environmentally driven autistic distress that requires accommodation rather than medication
• Set appropriate expectations: comorbid symptoms may improve, but core autistic features are not pharmacological targets

Modified CBT for Anxiety in ASD

Standard cognitive behavioral therapy (CBT) is the first-line psychotherapy for anxiety disorders in the general population, and adapted versions have the strongest evidence base among psychotherapies for anxiety in ASD. Several manualized programs have been developed and evaluated:

Facing Your Fears (Reaven et al., 2012) is a group-based CBT program for autistic children ages 8–14 with comorbid anxiety. A randomized controlled trial demonstrated clinically significant anxiety reduction in 50% of participants receiving the intervention versus 9% in the control group. Exploring Feelings (Attwood, 2004) and the Coping Cat adaptations for ASD have also shown positive results in controlled studies.

For autistic adults, the evidence base is thinner but growing. Adapted individual CBT incorporating the following modifications has shown promise:

• Increased use of visual supports: Written agendas, emotion thermometers, visual thought records, and concrete behavioral experiments replace abstract cognitive restructuring
• Longer treatment duration: 16–24 sessions rather than the standard 8–16, to allow for slower pace and repetition
• Concrete, explicit psychoeducation: Abstract concepts like cognitive distortions are explained using specific examples and rule-based frameworks that align with autistic cognitive styles
• Special interest integration: Using the individual's special interests as engagement tools and metaphors for therapeutic concepts
• Sensory accommodations: Addressing the therapy environment (lighting, seating, noise) and distinguishing sensory-driven anxiety from cognitive anxiety
• Reduced reliance on introspection: Given alexithymia prevalence, behavioral indicators of emotion are used alongside (or instead of) subjective emotion ratings
• Predictability in sessions: Consistent session structure reduces therapy-related anxiety

Meta-analytic evidence (Weston et al., 2016; Ung et al., 2015) supports adapted CBT for anxiety in autistic youth, with pooled effect sizes ranging from d = 0.47 to 1.12 depending on the outcome measure and comparison condition. These effect sizes are modest to large and generally comparable to (though slightly lower than) CBT effects for anxiety in non-autistic populations.

Adapted ERP for OCD in ASD

Exposure and response prevention (ERP), the gold-standard psychotherapy for OCD, requires adaptation for autistic individuals. Key modifications include:

• Extended psychoeducation phase to clearly differentiate OCD compulsions from autistic RRBs — only OCD behaviors are targeted
• Collaborative identification of which repetitive behaviors are OCD-driven versus autism-driven
• Visual and concrete fear hierarchies rather than abstract SUDS (Subjective Units of Distress) ratings
• Slower exposure progression with clear rationale at each step
• Explicit cognitive strategies that leverage the autistic individual's capacity for rule-learning and systematizing

Emerging evidence suggests that adapted ERP can be effective for OCD in ASD, though response rates may be somewhat lower — approximately 40–50% achieving clinically significant improvement compared to 55–65% in non-autistic OCD populations (Murray et al., 2015). Treatment duration may need to be extended.

Depression Interventions

The evidence base for treating depression specifically in autistic individuals is the weakest of the three comorbidities. Behavioral activation, which targets reduced engagement with rewarding activities and does not rely heavily on abstract cognitive skills, is theoretically well-suited for autistic individuals and is increasingly recommended. Small-scale studies of adapted CBT for depression in ASD have shown preliminary positive results, but no large RCTs exist. Acceptance and Commitment Therapy (ACT), with its emphasis on valued-action rather than cognitive restructuring, has emerged as a promising framework, though evidence remains preliminary (Pahnke et al., 2014).

A fundamental clinical question is whether comorbid psychiatric conditions in ASD should be treated sequentially (addressing one condition at a time) or through integrated approaches that address multiple conditions simultaneously.

The Case for Integrated Treatment

Several factors favor integrated approaches:

• Shared maintaining factors: Intolerance of uncertainty, alexithymia, and avoidance patterns maintain anxiety, depression, and OCD simultaneously. Targeting these transdiagnostic mechanisms may produce improvement across conditions.
• Environmental modifications benefit all conditions: Reducing masking demands, providing sensory accommodations, increasing predictability, and supporting access to restorative activities may alleviate anxiety, depression, and OCD symptoms simultaneously.
• Sequential treatment is often impractical: Many autistic individuals have multiple comorbid conditions. Treating each sequentially could require years of therapy, during which untreated conditions may worsen.

The Modular Approach to Therapy for Children (MATCH-ADTC) framework, which allows flexible deployment of evidence-based treatment modules for anxiety, depression, and conduct problems, has been proposed as a template for integrated treatment in autistic populations, though it has not been specifically validated for this use.

The Case for Sequential Treatment

In certain clinical scenarios, sequential approaches may be preferable:

• When severe anxiety prevents engagement with depression-focused interventions, anxiety treatment may need to come first
• When OCD rituals dominate the clinical picture, ERP may need to be prioritized before broader mood or anxiety work
• When autistic burnout is the primary presentation, environmental modification and restoration should precede introduction of demanding psychotherapeutic protocols

Practical Integration Model

In practice, many experienced clinicians adopt a phased approach that combines elements of both strategies:

Phase 1 — Foundation (sessions 1–6): Autism-informed psychoeducation, environmental accommodations, sensory and regulatory support, establishment of therapeutic alliance, and comprehensive functional assessment of all presenting concerns.

Phase 2 — Primary target (sessions 7–18): Evidence-based intervention for the condition causing greatest impairment, with concurrent monitoring of other conditions. The primary target is determined collaboratively with the client.

Phase 3 — Secondary targets and consolidation (sessions 19–24+): Shift to secondary conditions, generalization, relapse prevention, and long-term planning.

This phased model lacks formal RCT support but reflects the consensus emerging from specialized autism mental health services.

Psychiatric comorbidity significantly worsens prognosis across multiple domains for autistic individuals.

Functional Outcomes

Comorbid anxiety and depression in ASD are associated with lower employment rates, reduced social participation, lower quality of life, and increased dependence on support services. The National Longitudinal Transition Study-2 (NLTS2) data suggest that autistic adults with co-occurring psychiatric conditions have approximately 20–30% lower rates of competitive employment compared to autistic adults without comorbid conditions.

Treatment Resistance

Psychiatric conditions that co-occur with ASD tend to follow more chronic courses and show lower treatment response rates. The presence of ASD is associated with increased likelihood of treatment resistance in both anxiety and OCD. In the case of depression, unrecognized ASD may be a hidden contributor to the 30–40% of individuals who do not respond to standard antidepressant treatment — a finding with significant implications for treatment-resistant depression research.

Suicidality

The intersection of ASD, depression, and anxiety carries serious risk. Autistic adults are approximately 3–7 times more likely to die by suicide compared to the general population, and suicidal ideation is reported by approximately 30–66% of autistic adults in clinical samples (Cassidy et al., 2014; Hirvikoski et al., 2020). Depression, camouflaging/masking, unmet support needs, and late diagnosis are all identified risk factors. Comorbid anxiety may further elevate risk through increased distress and agitation. These data underscore the urgency of effective mental health assessment and intervention for autistic individuals.

Positive Prognostic Factors

Not all prognostic indicators are negative. Factors associated with better outcomes in comorbid ASD and psychiatric conditions include:

• Earlier identification of both ASD and comorbid conditions
• Access to autism-informed mental health services
• Strong social support and acceptance (particularly autistic peer networks)
• Environmental accommodations that reduce chronic stress
• Retention of special interests as sources of meaning and regulation
• Higher baseline cognitive and adaptive functioning (though this is a more modest predictor than often assumed)

Given the high bidirectional prevalence rates documented above, systematic screening is essential. The following recommendations reflect emerging clinical consensus:

When ASD Is the Index Diagnosis

• Screen for anxiety at every clinical contact, using adapted measures. The Anxiety Scale for Children with Autism Spectrum Disorder (ASC-ASD) (Rodgers et al., 2016) was specifically developed for this population and includes sensory anxiety and uncertainty anxiety subscales not captured by standard measures. For adults, the Adult Anxiety Scale-ASD (AAS-ASD) shows promising validation.
• Screen for depression at minimum annually and at transitions (school changes, employment changes, relationship losses). Standard instruments (PHQ-9, BDI-II) can be used with caution, but clinicians must account for overlap between autistic traits and depression items. The Patient Health Questionnaire-9 (PHQ-9) has received preliminary validation in autistic adults but may underdetect atypical presentations.
• Differentiate OCD from RRBs when repetitive behaviors increase in intensity, acquire distressing or feared-outcome content, or become ego-dystonic. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) can be used, ideally with clinician ratings that account for the RRB-OCD distinction.

When Anxiety, Depression, or OCD Is the Index Diagnosis

• Consider ASD screening when: social difficulties predate anxiety onset and extend beyond specific feared situations; treatment response to standard evidence-based interventions is unexpectedly poor; sensory sensitivities are prominent; restricted interests or need for sameness are reported; social communication difficulties are qualitatively different from social anxiety avoidance.
• Validated screening tools include the Autism Quotient-10 (AQ-10) for brief screening and the Social Responsiveness Scale-2 (SRS-2) for dimensional assessment. Positive screens should be followed by comprehensive diagnostic evaluation (ADOS-2, detailed developmental history).
• Particular vigilance is warranted for late-diagnosed adults, especially women and individuals with strong masking/camouflaging abilities, who are systematically underdiagnosed.

Critical Gaps in the Evidence Base

Despite the high prevalence and clinical significance of psychiatric comorbidity in ASD, the research base has substantial deficiencies:

• Autistic adults are vastly underrepresented in treatment research. The majority of intervention studies focus on children and adolescents, leaving adult clinicians with minimal evidence to guide practice.
• Pharmacological RCTs specifically examining SSRI efficacy for anxiety, depression, and OCD in autistic adults are almost nonexistent. Most prescribing is based on extrapolation from general population data and clinical experience.
• Suicidality research in ASD is in early stages, with a critical need for longitudinal studies identifying modifiable risk factors and testing prevention interventions.
• Women and gender-diverse autistic individuals are underrepresented in comorbidity research, despite evidence of higher rates of internalizing conditions and later diagnosis in these groups.
• Measures and diagnostic criteria have not been validated or adapted for the autistic population. Current DSM-5-TR criteria for anxiety, depression, and OCD do not include guidance on how these presentations may differ in autistic individuals.

Emerging Areas

Autistic burnout is receiving increasing research attention following qualitative studies by Raymaker et al. (2020). This construct — characterized by chronic exhaustion, loss of skills, and reduced stimulus tolerance following prolonged periods of masking and environmental demands — intersects with but is distinct from clinical depression. Burnout may represent a vulnerability state that precedes or co-occurs with formal psychiatric episodes.

Transdiagnostic interventions targeting intolerance of uncertainty, emotion regulation, and alexithymia are being developed and may prove more efficient than disorder-specific protocols for the complex comorbidity profiles typical in ASD. Early-phase trials of uncertainty-focused interventions (CUES program, Rodgers et al., 2017) have shown promising results.

Technology-assisted interventions, including internet-delivered adapted CBT and virtual reality exposure, may improve access for autistic individuals who find in-person therapy environments challenging. Initial feasibility studies are encouraging.

Neurodiversity-affirming therapeutic frameworks are increasingly shaping clinical practice. These approaches conceptualize the clinician's role as treating genuine psychiatric comorbidity (which causes distress) while affirming autistic identity and functioning style (which does not inherently require treatment). This framework distinguishes between supporting wellbeing and attempting to normalize autistic behavior, a distinction with significant implications for treatment targets and therapeutic alliance.