Identification of Psychosis Risk and Diagnosis of First-Episode Psychosis: Advice for Clinicians

Introduction

Psychotic-spectrum disorders such as schizophrenia have been recognized globally as among the most severe and debilitating health conditions that humans can experience.^1,2 Psychotic symptoms consist of positive symptoms such as hallucinations and delusions, negative symptoms such as diminished emotional expression and motivation, and disorganized symptoms such as incoherent speech and atypical behavior, and are often accompanied by disturbances in functioning, cognition, motor skills, and one’s basic sense of self.^3–5 Symptom onset typically occurs from late adolescence to one’s early twenties, an important developmental period referred to as emerging adulthood.⁶ The onset of psychotic illness during emerging adulthood can lead to tremendous disruptions in key developmental milestones such as the formation and maintenance of meaningful interpersonal relationships, pursuit of educational and career aspirations, and exploration of personal identity and independence.⁷

Importantly, research has shown that these functional disruptions unfold rapidly within the first few years following onset of psychotic illness.^8–10 Moreover, longer duration of untreated psychosis (i.e., the delay between onset of psychotic symptoms and receipt of adequate mental health care) has been repeatedly shown to relate to poorer outcomes, including increased psychotic symptom severity, suicide risk, and criminal justice involvement, reduced quality of life, social functioning impairment, and lower likelihood of remission and treatment response.^11–15 Finally, the initial years following onset of psychotic symptoms may represent a critical period for intervention, during which pharmacological and psychosocial treatments elicit the greatest treatment response.¹⁶ Therefore, intervention for youth early in the course of psychotic illness can be critical for improving chances of recovery.

Intervening among youth showing initial signs of psychosis is crucial, yet these signs can be difficult to identify and diagnose. This difficulty is in part due to the heterogeneity of clinical presentations of psychotic and related symptoms across individuals.^5,17 For example, one individual may struggle with persistent fears of being followed and blunted facial affect, whereas another may experience periods of hearing voices, speech disorganization, and intermittent depressive episodes. Added complexity of identifying early signs of psychosis comes with variability in symptom intensity and severity, as population-level genetic, neuropsychological, social, and environmental studies have consistently found that psychosis exists on a continuum.^18–20 An adolescent may present to the clinic reporting unusual perceptual experiences and odd beliefs, yet they may seem to be able to distinguish these experiences from reality, or perhaps these symptoms primarily occur when the person is exposed to reminders of a traumatic event. In such cases, it may not be readily apparent to the clinician whether the individual is exhibiting mild psychotic-like experiences common in the general population, early warning signs of psychosis, overt psychotic symptoms, or symptoms related to a non-psychotic illness.

At the lower end of the psychosis continuum, mild or transitory psychotic-like symptoms can include common experiences such as thinking that one’s cell phone is ringing or vibrating when it is not.^18,19 Attenuated psychotic or clinical high-risk symptoms refer to more significant early warning signs of psychosis, such as hearing indistinct voices whispering a few times per week, with some distress or behavior change such as reducing social activities due to discomfort in groups of people.²¹ Overt psychotic symptoms refer to symptoms meeting full clinical criteria for psychosis, such as hearing a clear voice making specific comments about one’s behavior daily, with marked distress or behavior change such as not leaving the house due to intense discomfort interacting with others.⁵ This psychosis continuum has been conceptualized as having a dimension of decreasing prevalence in the general population coinciding with a dimension of increasing severity.¹⁸ Another key factor to consider is level of insight into the symptom, or the extent to which an individual can distinguish the symptom from reality, which decreases along the continuum from mild psychotic-like symptoms to overt psychotic symptoms.

Accurate assessment of where a person’s symptoms fall on the psychosis continuum is important for both: 1) clarifying whether intervention is warranted; and 2) selecting the appropriate evidence-based interventions among available options. With regard to the former, for example, youth experiencing mild psychotic-like symptoms in some cases might not warrant clinical attention, whereas youth exhibiting distressing, attenuated psychotic symptoms may benefit from intervention (e.g., step-based care^22,23), which could lower their risk of developing a psychotic disorder.²⁴ With regard to the latter, antipsychotic medications have demonstrated efficacy for many individuals with first-episode psychosis (FEP)^25–27 but are currently discouraged as front-line treatments for individuals with attenuated psychotic symptoms given limited evidence of efficacy for preventing conversion to psychosis and high side effect burden.^24,28,29

Overall, the purpose of this article is to provide clinicians with a framework for determining whether a patient is experiencing symptoms of FEP or early warning signs which may indicate heightened risk for developing psychosis. We will begin by outlining the defining characteristics of FEP and psychosis-risk syndromes, as well as common assessment tools used to diagnose these conditions. Next, we will provide examples of differential diagnoses which have phenotypic overlap with psychotic illnesses but for which different treatments may be indicated. Finally, we will conclude with an overview of approaches toward outreach and screening for psychosis in the clinic and community.

Clinical Characteristics of First-Episode Psychosis

Defining First-Episode Psychosis

FEP is a term used to describe a recent onset of overt psychotic symptoms, particularly delusions and/or hallucinations that are at times indistinguishable from reality, or disorganized speech that is tangential or incoherent.¹⁸ These symptoms occur frequently (e.g., averaging at least 1 hour per day, 4 days per week for 1 month³⁰) and/or are seriously disorganizing or dangerous to oneself or others. The term “first-episode psychosis” often refers to the experience of psychotic symptoms with an onset within the past 2–5 years rather than exclusively referring to the individual’s initial psychotic episode. A more accurate term may therefore be “recent-onset psychosis.”³¹ However, given the widespread usage of the term FEP in clinics and research literature, we use it here for consistency.

Symptoms of FEP tend to present in the late teenage to early adult years of life.^3,32 The etiology of psychotic-spectrum disorders is complex, with research suggesting these are neurodevelopmental disorders which emerge through gene-environment interactions.³³ Individuals with FEP may meet criteria for a variety of psychiatric disorders outlined in current diagnostic systems.^3,34 Schizophrenia is the prototypical psychotic-spectrum disorder, consisting of two or more symptoms of delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, and negative symptoms, lasting at least six months and resulting in functional impairment. Individuals with FEP may also meet criteria for schizophreniform disorder (i.e., schizophrenia symptoms lasting less than six months with no requirement of functional decline), brief psychotic disorder (i.e., one or more positive or disorganized symptoms of psychosis lasting between one day and one month), schizoaffective disorder (i.e., concurrent symptoms of schizophrenia and a major depressive/manic episode, with psychotic symptoms persisting for at least two weeks without mood symptoms, and mood symptoms present for the majority of the illness), major depressive disorder or bipolar disorder with psychotic features (i.e., psychotic symptoms present primarily within mood episodes), delusional disorder (i.e., delusions as the primary psychotic symptom, with functioning intact aside from the impact of the delusions), or an unspecified psychotic-spectrum disorder, among others.

While discrete psychotic disorder diagnoses have clinical and practical utility (e.g., for assessing comorbid mood episodes, insurance billing), these disorders often share more overlap than differences with regard to neurobiology, cognitive function, and other illness features.³⁵ Specific diagnoses may be even less clear among individuals with FEP than those with longstanding psychotic illness, as consistent patterns of co-occurring symptoms can take years to emerge. Therefore, here we focus on the identification and diagnosis of FEP generally rather than specific psychotic disorders. Nevertheless, assessment over time of affective components of FEP (e.g., co-occurring depressive and/or manic episodes) and specific symptom profiles is warranted to inform pharmacological and psychological interventions. Additionally, clinicians should rule out psychosis due to physiological effects of drugs of abuse, medications, and medical conditions prior to intervention.

Overall, though the specific clinical presentation of FEP is diverse and individualized across youth, many symptoms will fall into one of several characteristic symptom clusters: positive, negative, and disorganization of thinking, speech, and/or behavior.

Positive Symptoms

Positive symptoms are perhaps the most defining feature of psychotic disorders and are characterized by alterations in perception and thinking that often lead to significant impact on behavior and functioning.⁵ In the context of psychosis, “positive” denotes the addition of sensory and/or thought experiences that would not otherwise be present, namely hallucinations and delusions. Though positive symptoms are often highly distressing, they are the domain of psychotic symptoms most responsive to clinical intervention.³⁶

Hallucinations within psychotic disorders describe sensory experiences that occur in the absence of external stimuli (i.e., another person in the same situation would not share the sensory experience) which are perceived as true stimuli. Hallucinations can occur in any sensory modality (i.e., visual, auditory, olfactory, gustatory, tactile), but most commonly occur in the auditory modality among individuals with first-episode³⁷ and longstanding³ psychosis. Common types of auditory hallucinations among individuals with FEP include second-person voices making negative or derogatory comments and command hallucinations instructing the experiencer to take certain actions. Common types of visual hallucinations among individuals with psychotic disorders include seeing distressing images of animals, people, faces, objects, or events (e.g., a lit fire in front of them).³⁸

Delusions are tenaciously held, false beliefs that are not responsive to contrary information⁵ and are inconsistent with the individual’s cultural norms.³⁹ The content and expression of delusional beliefs is highly individualized among people with psychotic disorders. The most common delusional themes among individuals with FEP³⁷ and longstanding⁵ psychosis are persecution (i.e., false belief of being targeted or followed by a malicious person or entity, such as belief of being monitored by hidden cameras) and reference (i.e., false belief that there are messages or significant meaning in otherwise unremarkable aspects of the surrounding environment, such as belief of receiving special messages through the television). Other common delusional themes include grandiosity, thought insertion and withdrawal, guilt, mind reading, somatic, nihilistic, erotomaniac, and loss of control, among others.³

Negative Symptoms

Negative symptoms of psychosis are characterized by an attenuation or absence of various normative emotional, behavioral, and experiential processes.^40,41 Negative symptoms can include reductions in motivation and interest, decreased social drive and social behavior, diminished emotional experience and/or expression, and a reduced ability to experience pleasure.⁴² Negative symptoms can be pervasive during the course of FEP;⁴³ they are often treatment-resistant, tending to persist even when other aspects of illness are well-managed.⁴⁴ Individuals with prominent negative symptoms during FEP tend to have poorer clinical outcomes over time.⁴⁵ At the same time, negative symptoms can fluctuate early in the course of illness,⁴⁶ with evidence that many individuals with prominent negative symptoms at the onset of FEP experience a significant reduction in these symptoms in the first year of treatment.⁴⁷

Disorganized Symptoms

Many individuals with psychosis experience symptoms of disorganization impacting thinking, speech, and/or behavior.⁵ Disorganized speech and disrupted communication are common among individuals with psychosis and can manifest in a variety of ways, ranging from mild difficulties with tangential speech to moderate or severe impairments that interfere with one’s ability to communicate even basic meaning to others.^5,48 Disorganized behavior also exists on a continuum of severity and can include odd or inappropriate displays of affect, wearing clothing that is grossly mismatched to the weather or situation, and changes in movements and overall motoric activity.⁵ Though current diagnostic systems consider disorganized symptoms as a distinct symptom domain,³ these symptoms also overlap with the negative and positive symptom domains.^49,50

Associated Clinical Features and Comorbidity

Though the positive, negative, and disorganized symptom clusters are highly representative of psychotic disorders, additional signs and symptoms are also common among individuals with FEP. In particular, individuals with FEP have prominent cognitive impairments across domains (e.g., attention, memory, processing speed)⁵¹ by the time of illness onset.⁵² Though cognitive impairment is robustly linked to functional outcomes in more longstanding psychotic disorders,⁵³ the associations between cognitive impairment and functioning among individuals with FEP are less clear.^54,55 Many individuals with FEP also experience diminished insight or awareness of illness,⁵⁶ which has been associated with longer inpatient psychiatric hospitalizations.⁵⁷

Individuals with FEP have high rates of psychiatric comorbidity in the early course of illness,⁵⁸ including mood disorders, anxiety, and substance use disorders.^59,60 Many comorbid conditions and cognitive impairment predate the onset of psychosis and may represent underlying risk factors for FEP.⁶¹ Individuals with FEP also have elevated rates of physical health comorbidities, including elevated rates of cardiometabolic conditions (i.e., elevated blood pressure and blood lipid levels).⁶² Longitudinal cohort studies suggest that, overall, individuals with FEP have an 11-fold increase in all-cause mortality in the 10 years following illness onset.⁶³ Finally, individuals with FEP are at elevated risk for suicide and self-harm,⁶⁴ particularly in the first three months following the initial diagnosis of a psychotic disorder.⁶⁵ An estimated 5–10% of individuals with schizophrenia die by suicide,⁶⁶ and suicide is the leading cause of death among individuals with a psychotic disorder in the first five years following initial diagnosis.⁶⁷

Clinical Characteristics of Psychosis Risk

Defining Clinical High Risk for Psychosis

Psychotic disorders are often preceded by a phase in which psychotic-like experiences become progressively more severe while daily functioning deteriorates, culminating in a full psychotic episode.⁶⁸ “Clinical high risk for psychosis” (CHR-P) is a term that has been created to identify and provide preventative care to youth who are exhibiting these early warning signs prior to onset of a full psychotic episode. In addition to CHR-P, other commonly used terms for this state are “at-risk mental state” and “ultra-high risk for psychosis.”^24,69 While previously referred to as the psychosis “prodrome”, usage of this term is decreasing as the majority of individuals who exhibit early warning signs of psychosis do not go on to develop a psychotic disorder.⁷⁰ The CHR-P syndrome is also transdiagnostic and dimensional in the sense that it confers shared risk for all psychotic disorders, rather than specific risk for specific psychotic disorders (e.g., schizophrenia).⁷¹

Three subtypes of psychosis-risk syndromes are often recognized.^21,30,69 The most common CHR-P syndrome subtype is attenuated positive symptom syndrome (APSS), comprising around 85% of cases.⁷² APSS is identified by the presence of persistent attenuated positive psychotic symptoms, occurring at least once per week for a month or more. A second CHR-P subtype is brief intermittent psychotic syndrome (BIPS), comprising around 10% of cases.⁷² BIPS is identified by the presence of overt psychotic symptoms which occur intermittently and spontaneously resolve after a short span of time (i.e., lasting for at least several minutes, once per month, but occurring less than one hour per day, four days per week). A third CHR-P subtype is genetic risk and functional decline (GRD), comprising around 5% of cases.⁷² GRD is identified by genetic risk (i.e., a psychotic disorder in a first-degree relative or the individual meeting criteria for schizotypal personality disorder) plus significant decline in functioning (i.e., a greater than 30% drop in Global Assessment of Functioning [GAF]⁷³ scores within one year).

Finally, psychosis risk has also been conceptualized through the lens of “basic symptoms.”⁷⁴ Basic symptoms are subtle, subjectively observed alterations in thinking, speech, perception, motor function, stress tolerance, affect, drive, and self-experience, which are posited to be early manifestations of the neurobiological processes underlying psychosis. These symptoms can fluctuate over time and might not be observable by others. While they can precede a psychotic episode⁷⁵ (and can even precede attenuated psychotic or CHR-P symptoms), basic symptoms may also be present during an acute psychotic episode as well as residual states of illness.⁷⁴

Attenuated Positive Psychotic Symptoms

Most cases of individuals at CHR-P are identified via the presence of attenuated positive psychotic symptoms.^21,76 Onset of these symptoms may occur following a stressful event (e.g., parents’ divorce, peer conflict, death of a loved one, other traumatic event) or following no apparent stressors. For some individuals, attenuated positive symptoms are experienced as longstanding since childhood but may become more frequent and impairing over time, and for others, they emerge for the first time in adolescence or young adulthood. Domains of attenuated positive symptoms are subthreshold delusional beliefs, subthreshold hallucinatory experiences, and subthreshold disorganized thought and speech. For example, an individual at CHR-P may begin to experience distressing thoughts that they are living in a simulation (i.e., unusual thought content), thoughts that others are laughing at them or playing tricks on them (i.e., suspiciousness), ideas that they have special talents like the ability to predict the future (i.e., grandiosity), hearing footsteps or doors slamming when no one is present (i.e., perceptual abnormalities), and/or difficulties connecting their thoughts and conversing clearly with others (i.e., disorganized communication). See Table 1 for further examples and comparisons with symptoms at other stages in the psychosis continuum.

Table 1 Example Experiences Spanning the Psychosis Continuum

Most people in the general population have had one or more of the mild experiences described in Table 1 in their lifetime, consistent with fully dimensional models of a psychosis continuum in the general population.²⁰ To meet criteria for the APSS CHR-P syndrome, attenuated positive symptoms must be frequent (e.g., occurring at least once a week), perceived as significant or cause some level of distress, and may interfere with one’s daily functioning (e.g., an individual refrains from showering at night due to worries about someone breaking into their apartment), among other criteria.²¹ Unlike overt psychotic symptoms (Table 1), attenuated psychotic symptoms include some capacity to distinguish symptoms from reality (in APSS subtype) or include full delusional conviction that is brief and intermittent (BIPS subtype). Of note, it is possible for individuals with psychotic-spectrum disorders to experience attenuated symptoms after already experiencing overt psychotic symptoms, in which case these would be classified as residual psychotic symptoms.

Associated Clinical Features and Comorbidity

Individuals at CHR-P may also exhibit attenuated psychotic symptoms in domains other than positive symptoms, such as negative (e.g., avolition, anhedonia, blunted affect), disorganized (e.g., odd behavior or appearance), and general (e.g., sleep and mood disturbance) symptoms.^21,30 However, attenuated positive symptoms are primarily used in the diagnosis of psychosis-risk syndromes.

Youth at CHR-P also typically experience mild-to-moderate cognitive impairment across many cognitive domains compared their typically developing peers,⁷⁷ which often persists even among individuals whose attenuated psychotic symptoms remit over time.⁷⁸ Additionally, youth meeting CHR-P criteria tend to retrospectively report poorer premorbid functioning (i.e., functioning up to one year prior to baseline assessments) in social and academic domains in proportion to the severity of their attenuated negative symptoms.⁷⁹ Premorbid social functioning may be particularly relevant, as rapid declines in social functioning are known to increase risk for psychotic disorders within the clinical high-risk syndrome.⁸⁰ Individuals at CHR-P are also at elevated risk for suicide,^81,82 with one meta-analysis indicating that 66% of individuals reported suicidal ideation and 18% reported suicide attempts, although there were high levels of heterogeneity across studies.⁸³

Most individuals meeting CHR-P also meet criteria for at least one other psychiatric disorder (roughly 80%), most commonly mood (45%), anxiety (35%), trauma-related (30%), and personality (25%) disorders (especially schizotypal personality disorder).⁸⁴ Some comorbid disorders remit over time; at follow-up durations longer than 2 years, prevalence of comorbid disorders decreases to around 45–50%. This suggests that individuals are more likely to be identified as being at CHR-P at times when comorbid psychopathology is particularly pronounced.

Likelihood of Developing a Psychotic Disorder

When individuals at CHR-P develop a psychotic disorder, they are said to have “converted” or “transitioned” to psychosis. Overall, only a minority of clinical high-risk cases convert to psychosis within typical follow-up periods. At one year since presentation to the clinic, approximately 15% of individuals at CHR-P have converted to a psychotic disorder; at two years, roughly 20% have converted; and at four years the conversion rate plateaus between 25% and 30%.⁷⁰ Rates of conversion to psychosis differ between the three subtypes, with conversion being more likely in the BIPS group and less likely in the GRD group.⁷² Conversion is more likely among individuals with more severe functional impairment (especially recent declines in social functioning),⁸⁵ more severe attenuated positive psychotic symptoms, and among those who are male, unemployed, and/or have trauma histories.⁸⁶

Personalized risk calculators have been developed to estimate individuals’ risk of conversion.⁸⁵ Conversion rates have decreased somewhat over time, potentially due to a combination of earlier treatment⁸⁷ and case identification strategies based on broad outreach among clinicians and in the general population.^88,89 In general, help-seeking individuals appear to be at higher risk of conversion to psychosis than individuals identified by screening or outreach in the general population.⁹⁰ However, individuals who do not convert to psychosis do not necessarily experience symptomatic or functional remission; around half experience persistent or worsening symptoms (roughly 60%)⁷⁸ and functional impairment (roughly 40–45%),⁹¹ despite not developing clinical psychotic disorders.

Diagnostic Assessment Tools

In this section, we provide a brief overview of several assessment tools that clinicians and researchers use to diagnose psychosis-risk syndromes, FEP, and particular psychotic-spectrum disorders (see Table 2). Many of these tools require specialized training and formal certification prior to use in clinical and research settings. There are numerous additional scales beyond those described here which assess level of symptom severity across the psychosis continuum.^49,92,93

Table 2 Assessment Tools for Psychosis-Risk Syndromes, FEP, and Psychotic-Spectrum Disorders

Tools for Diagnosing Psychosis-Risk Syndromes

The Structured Interview for Psychosis-risk Syndromes (SIPS)^21,30 and the Comprehensive Assessment of At-Risk Mental States (CAARMS)⁶⁹ are semi-structured interviews designed to diagnose CHR-P syndromes (SIPS) or at-risk mental states (CAARMS) and FEP among treatment-seeking individuals. In clinical practice, the clinical high-risk state and the at-risk mental state are quite similar, and a new measure has been developed to harmonize the two sets of criteria.^94,106 The Bonn Scale for the Assessment of Basic Symptoms (BSABS)⁹⁵ and the Schizophrenia Proneness Instrument (SPI)^96,97 are semi-structured interviews used to assess basic symptoms, which are also indicative of psychosis risk.⁷⁵

The SIPS and the CAARMS both include assessment of attenuated positive, negative, disorganized, and general psychopathology symptoms, among other domains. Psychosis-risk syndromes defined using these tools include: 1) APSS in SIPS; attenuated psychosis in CAARMS; 2) brief (limited) intermittent psychosis syndrome (BIPS in SIPS; BLIPS in CAARMS); and 3) genetic risk and functional decline (GRD in SIPS; vulnerability group in CAARMS); see Clinical Characteristics of Psychosis Risk section for further detail. These diagnoses are not mutually exclusive (e.g., an individual may have APSS and GRD). Attenuated positive symptoms on these measures include unusual thought content, perceptual abnormalities, disorganized communication (SIPS and CAARMS), non-bizarre ideas (CAARMS), and suspiciousness and grandiosity (SIPS). Symptoms are each rated on a 0–6 scale considering levels of severity, distress, behavioral impact, and conviction (i.e., insight, or ability to distinguish the symptom from reality). Ratings of 0–2 are considered to be within the range of typical functioning, ratings of 3–5 are within the clinical high-risk range, and a rating of 6 indicates overt psychosis. In the SIPS, psychosis-risk diagnoses are given only if attenuated positive symptoms are not better explained by another psychiatric disorder. In the CAARMS, diagnosable psychosis-risk syndromes require that symptoms be present in the past year.

The BSABS⁹⁵ and the SPI^96,97 assess basic symptoms in domains such as alterations in energy, drive, stress tolerance, emotional reactivity, cognition, attention, depersonalization, perception, motor function, self-experience, and central-vegetative function (e.g., sleep, appetite, libido, heart rate, thermoregulation). Psychosis-risk criteria using these tools primarily rely on cognitive and perceptual disturbances (e.g., thought interference, thought blockage, unstable ideas of reference, decreased ability to discriminate between fantasies and true memories, visual and acoustic perception disturbances). Basic symptom cognitive disturbances measured in conjunction with SIPS CHR-P criteria have more accurately predicted conversion to psychosis than either set of criteria in isolation,¹⁰⁷ suggesting clinical utility in combining psychosis-risk assessments.

Of note, inclusion of psychosis-risk syndromes in psychiatric diagnostic classification systems has been debated.¹⁰⁸ “Attenuated psychosis syndrome” currently resides in the “Conditions for Further Study” section of the DSM-V and as a specifier of other specified psychotic disorders rather than being represented as a formal diagnostic category. Opponents of adding psychosis-risk syndromes as clinical diagnoses cite concerns of potential high false positive rates due to symptom ambiguity and low overall incidence of conversion to psychotic disorders, increases in unwarranted treatment (e.g., antipsychotic medication), and unnecessary stigma to diagnosed individuals.^108,109 In contrast, proponents argue that formalizing psychosis-risk syndromes as clinical diagnoses would promote early identification and intervention for help-seeking individuals, catalyze clinical trials to strengthen the evidence-base for relevant treatments, and potentially decrease unwarranted treatment by reducing rates of misdiagnosis.¹¹⁰ Lastly, some evidence suggests that stigma may be more related to psychosis-risk symptoms than the diagnostic label itself.¹¹¹ Proponents for formalizing the diagnosis argue that stigma is unlikely to be greater for psychosis-risk diagnoses than the potentially inaccurate diagnoses that these individuals are already receiving, and regardless, increased access to care may outweigh any increases in stigma.¹¹⁰

Tools for Diagnosing First-Episode Psychosis and Psychotic-Spectrum Disorders

Psychosis-risk assessment tools (e.g., SIPS, CAARMS) are useful for assessing for the presence of FEP in addition to diagnosing clinical-high risk and at-risk mental state symptoms. These tools include ratings systems which offer a clear delineation between symptoms which fall within ranges of normative functioning, CHR-P, and overt psychosis indicative of FEP among youth. For example, if unusual thought patterns, perceptual abnormalities, and/or communication disturbances are rated as a 6 in severity on the SIPS, occur frequently for sustained periods, are not accounted for by another psychiatric illness, and began or worsened within the past 2–5 years, the individual might meet criteria for FEP.³⁰

If an individual is determined to be experiencing overt psychotic symptoms, a clinician may assess whether their symptoms meet criteria for a specific psychotic-spectrum disorder diagnosis (e.g., schizophrenia, schizoaffective disorder, delusional disorder, etc.) using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5)³ or the International Classification of Diseases (ICD–11).³⁴ Common clinical interviews used to assess these diagnostic criteria include the Structured Clinical Interview for DSM-5,⁹⁸ the Schedule for Affective Disorders and Schizophrenia⁹⁹ (and the K-SADS youth version¹⁰⁰), and the Mini International Neuropsychiatric Interview,¹¹² among others.

Differential Diagnosis

There are many instances in which a young person presents to the clinic with psychotic-like symptoms (e.g., odd beliefs, perceptual abnormalities, unusual speech patterns), and it is not clear whether they are experiencing overt psychotic symptoms, clinical high-risk symptoms, or symptoms of another psychiatric illness altogether.¹¹³ Moreover, comorbid psychiatric conditions are the norm rather than the exception for individuals with psychotic disorders, making differential diagnosis a challenging task for clinicians.¹¹⁴ Differential diagnosis can have important clinical implications, influencing access to care and treatment selection. See Table 3 for case examples of client presenting concerns, preliminary clinical impressions, and potential referrals. Next, we provide examples and recommendations for differential diagnosis with a focus on three diagnostic categories that have significant phenotypic overlap with psychotic disorders: 1) autism spectrum disorder; 2) obsessive-compulsive disorder; and 3) post-traumatic stress disorder.

Table 3 Case Examples of Patients Arriving to Clinic with Presenting Concerns, Preliminary Clinical Impressions, and Potential Referrals

Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication difficulties and restricted or repetitive patterns of behavior or interests.³ Early conceptualizations of ASD and schizophrenia recognized their phenotypic overlap, with autism initially considered to be a symptom of schizophrenia.¹¹⁵ While current diagnostic systems treat ASD and psychotic disorders as distinct,^3,34 their overlap and differentiation are still debated.¹¹⁶ For example, social communication difficulties among individuals with ASD can be misperceived as negative symptoms of psychosis, disorganized thinking, and paranoia. Additionally, ASD symptoms of sensory sensitivities and idiosyncratic speech and thinking patterns can be misperceived as hallucinations and delusions. We offer the following recommendations to aid in the differential diagnosis of these disorders.

First, age of symptom onset and functional impairment typically begins in childhood for ASD and emerging adulthood for psychotic disorders.³ Second, tangential, stereotyped, or unusual speech which returns to specific or restricted topics of interest and reflect an individual’s baseline speech patterns may be more characteristic of ASD than psychotic disorders.¹¹⁷ Third, as distinguishing characteristics of psychotic disorders are overt hallucinations and delusions, asking clarifying questions and eliciting specific examples is critical for differential diagnosis. For instance, an individual with ASD may endorse seeing or hearing things that others do not see due to hypersensitivity to sensory stimuli.¹¹⁸ An individual with ASD may also endorse hearing voices when no one is present for several reasons other than experiencing psychosis, such as: 1) concrete interpretation of the question (e.g., they hear voices on the radio); or 2) vivid imaginative experiences (e.g., difficulty distinguishing hearing their own thoughts in their head from an external voice).^119–121

Importantly, there is not always a clear distinction between ASD and psychotic disorders even with rigorous clinical assessment,^116,117 as there is substantial comorbidity^122,123 and genetic overlap.¹²⁴ While some individuals with ASD also experience attenuated positive symptoms, rates of transitioning from clinical high-risk state to a psychotic disorder do not appear to be impacted by the presence of ASD.¹²⁵ Overall, if an individual is ultimately exhibiting comorbid ASD and psychotic illness, clinical services addressing the symptoms associated with distress and functional impairment from either or both conditions should be carefully considered.

Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is characterized by: 1) recurrent and persistent thoughts that cause significant distress and are perceived as intrusive or unwanted (i.e., obsessions); and 2) repetitive behaviors or mental acts (i.e., compulsions) that serve to reduce the distress associated with the obsession.³ Symptoms of OCD and psychotic disorders have phenotypic overlap, such as obsessions and compulsions which may present similarly to delusional beliefs and corresponding avoidance behaviors. To further complicate matters, the DSM-5 includes a “with delusional beliefs” OCD specifier, indicating full conviction of the obsessional belief(s). The DSM-5 provides few recommendations for differentiating between OCD and psychotic disorders, merely noting that obsessions and compulsions are not diagnostic criteria for psychotic disorders, and hallucinations are not diagnostic criteria for OCD. Thus, we offer the following additional recommendations to aid in their differential diagnosis.

First, the content of the belief might be useful in distinguishing between obsessions and delusions.¹²⁶ For instance, common themes in psychotic delusions include persecution, grandiosity, guilt, religion, thought insertion and withdrawal, thought broadcasting, mind reading, delusions of reference, and somatic delusions. In contrast, common themes for obsessions include contamination, violent or sexual thoughts, and “not just right experiences” (i.e., unsettling feeling that something is not as it should be). Second, the intrusive quality of obsessions and the experiencer’s retained insight into their excessive nature may be useful for differentiating obsessions and delusions.¹²⁶ Finally, the repetitive, ritualistic, and often time-consuming nature of compulsions might be useful in differentiating between compulsions and psychosis-related avoidance behaviors. For instance, checking locks a specified number of times might be more characteristic of OCD, whereas using multiple locks, blocking windows and doorways, and using surveillance strategies (e.g., security systems) might be more characteristic of psychotic paranoia. However, it is important to note that OCD and psychotic disorders can be comorbid,¹²⁷ and clinicians should consider the possibility of co-occurring disorders.

Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a trauma-related disorder characterized by the experience of a traumatic event (exposure to an actual or threatened death, serious injury, or sexual violence) followed by at least one month of re-experiencing or intrusive symptoms, avoidance behaviors, negative alterations in mood or cognition, and increased arousal or reactivity.³ Trauma history is strikingly high among individuals with psychotic disorders (~28 to 73%),¹²⁸ and severe symptoms of PTSD can overlap with the phenotypic expression of psychotic disorders.¹²⁹ For instance, hypervigilance may overlap with paranoia, flashbacks may overlap with hallucinations, and both disorders can lead to significant occupational and social impairment.¹²⁹ To aid in the differential diagnosis of PTSD and psychotic disorders, we offer the following recommendations.

First, hypervigilance and paranoia might be differentiated by inquiring about the patient’s specific reasons for having such concerns. Trauma-specific mistrust may be more characteristic of PTSD (e.g., fear of future encounters with a specific male perpetrator, generalized fear of all men), whereas fears that are broader or unrelated to the trauma may be more characteristic of psychotic disorders (e.g., fear of all people, fear of the government). Second, the content of hallucinations in the context of PTSD is often trauma-specific and includes themes related to threat (e.g., hearing the perpetrators voice),¹³⁰ whereas hallucinations in psychotic disorders may have broader themes and are rarely solely trauma-specific. Thorough assessment of the nature and timeline of the trauma can also be helpful for differential diagnosis. For example, psychotic-like symptoms which occur primarily in response to trauma cues (e.g., situational triggers, anniversary of the trauma) may be more indicative of PTSD, whereas psychotic-like symptoms which occur without a particular cue or in response to stressors more broadly may be more indicative of a psychotic disorder. Importantly, studies have demonstrated that common assessment tools for PTSD (e.g., CAPS-5, PCL) are valid for use among individuals with psychotic disorders,^131,132 and researchers have also developed modified versions of these tools to assess for co-occurring PTSD among individuals with schizophrenia.¹³¹

Transdiagnostic Approaches

In addition to the recommendations above for aiding in differential diagnosis, we encourage clinicians to identify underlying themes (e.g., mistrust, avoidance, social difficulties) that might be useful treatment targets that can guide treatment selection among individuals with complex or comorbid presentations. For instance, avoidance behaviors may be addressed using behavioral techniques (e.g., exposures and reality testing) regardless of whether the patient is experiencing symptoms of OCD, overt psychosis, or attenuated psychosis. Additionally, transdiagnostic treatment approaches (e.g., The Unified Protocol)¹³³ are utilized for treating patients with various types of emotional disturbances, including those at CHR-P.²² Finally, many evidence-based interventions designed for other diagnoses (e.g., Cognitive Processing Therapy for PTSD)¹³⁴ can be useful for addressing comorbidities among individuals with psychotic-spectrum disorders.

Screening and Outreach

Despite a rapid increase in specialized clinical services for individuals at CHR-P²² and individuals with FEP,¹³⁵ the majority of individuals early in the course of a psychotic or putative psychotic disorder do not access such specialized treatment programs. Consequently, outreach and recruitment activities are critical components for identifying individuals early in the course of a psychotic disorder to ensure access to specialized care during the time their illnesses are most malleable.¹³⁶ Common strategies employed to date include use of screening measures and outreach campaigns.

Screening Measures

Identification and diagnosis of individuals at CHR-P and those with FEP typically requires completion of lengthy clinical assessments such as the SIPS^21,30 or the SCID-5.⁹⁸ Although these assessments are the gold standard for identifying individuals at risk for psychosis and those experiencing FEP, they require significant training and time to complete, making them of limited use to many clinicians.¹³⁷ Consequently, there has been increased interest in developing and validating brief, self-report assessments that can be administered in the general population to screen individuals prior to completing time-intensive clinical assessments.

Several questionnaires specifically developed to screen for attenuated or overt psychotic symptoms have shown promise in identifying individuals at CHR-P and individuals with FEP, including the Prodromal Questionnaire-Brief Version,¹⁰¹ the PRIME Screen-Revised,¹⁰³ and the Youth Psychosis At-Risk Questionnaire,¹⁰⁴ among others^102,105,138 (Table 2). Validity and accuracy of these measures has also been examined across cultures.^139–141 Some common mental health assessments not designed to screen for psychosis (e.g., Child Behavior Checklist¹⁴² and both the self-report and parent-report versions of the Behavior Assessment System for Children¹⁴³) have also shown promise as screening measures to identify individuals who may be early in the course of a psychotic disorder.

However, several limitations hinder the use of such measures as universal screening tools, including the lack of normative, demographic-specific data to inform thresholds for identifying psychosis or psychosis risk,¹⁴⁴ the lack of symptom overlap across measures,¹⁴⁵ and many scales’ exclusive focus on positive (or attenuated positive) symptoms of psychosis.¹⁴⁶ Additionally, the ability of such scales to accurately differentiate individuals at CHR-P from those already experiencing overt psychotic symptoms is often limited.¹⁰¹ Finally, screening measures for psychosis and psychosis risk are in need of cross-cultural validation, as they may artificially inflate perceived rates of psychosis-related pathology among individuals from underrepresented and underserved backgrounds due to potential factors such as experiences of prejudice, crime, trauma, and variations in cultural norms.^147–150

Outreach Campaigns

Many early psychosis intervention services have paired their clinical programming with an active outreach campaign designed to facilitate early identification and referrals to their program. To date, such campaigns are most well operationalized within the context of FEP programs, and their presence is often considered a marker of a high fidelity program.¹⁵¹ Through such activities, FEP clinical services strive to facilitate the early identification and referral of individuals to their service as soon as possible following the onset of psychotic symptoms with the goal of reducing the duration of untreated psychosis—a key, modifiable risk factor for which longer duration of untreated psychosis is associated with a worse course of illness for individuals with a psychotic disorder.^14,152 Yet, despite the near ubiquity of outreach campaigns within FEP programs, available evidence questions their effectiveness in reducing duration of untreated psychosis among program participants.^153,154 These findings may be in part due to heterogeneity in how both duration of untreated psychosis and FEP were operationalized across studies.¹⁵⁴

The presence of structured outreach activities designed to facilitate early care are less ubiquitous in programs for individuals at CHR-P than among FEP programs.¹⁵⁵ Although research on outreach campaigns for clinical high-risk programs is limited, available evidence suggests that a combined outreach program geared toward simultaneously increasing early access for individuals at CHR-P and individuals with FEP may increase eligible referrals to a CHR-P clinical service.¹⁵⁶ More research is needed on the design and delivery of effective community outreach campaigns to facilitate early identification and access to care for individuals at CHR-P. Lastly, expansion of early psychosis detection campaigns is particularly needed within underserved communities which often have limited access to mental health care, such as among individuals from underrepresented racial and ethnic groups and those within criminal justice settings.^157–159

Conclusion

Psychotic-spectrum disorders and psychosis-risk states are complex, heterogeneous, frequently comorbid with other conditions, and lie on a continuum of human experience. Growing evidence indicates that the early phase of psychotic illness is a critical period in which intervention has maximum benefit for individuals in their recovery. Therefore, this review aimed to provide clinicians with a framework for identifying and diagnosing psychotic symptoms, attenuated psychotic symptoms, and psychotic-like experiences to increase diagnostic clarity for help-seeking youth. Screening and outreach campaigns are particularly important across a variety of key settings (including schools, hospitals, criminal justice settings, and the general public) to promote early detection of psychosis and rapidly connect individuals to clinical care. Given that early signs and symptoms of psychosis often emerge alongside other forms of psychopathology (e.g., anxiety, mood disturbances, trauma-related illness), a transdiagnostic approach to identification and treatment is strongly encouraged. Such work will address issues related to high rates of psychiatric comorbidity and promote overall wellness among youth.