Schizotypal Personality Disorder

Etiology

When schizotypal personality disorder was introduced in the DSM-III, it was based in part on the study of family members of individuals with schizophrenia. Although older literature suggests that many individuals diagnosed with schizotypal personality disorder progress to schizophrenia, recent research does not support this.[6] There is also disagreement on what constitutes schizotypal personality disorder and its relationship with other Cluster A personality disorders and schizophrenia.

Some common chromosome regions are shared by schizotypal personality disorder and schizophrenia.[6] Among possible candidate genes, the dystrobrevin-binding protein 1 (DTNBP1) gene located on chromosome 6q22.3, which codes for a synaptic protein dysbindin 1, has been associated with schizophrenia and paranoid schizotypy. Functional alterations in the catechol-O-methyltransferase gene (COMT) in the form of a single-nucleotide polymorphism on codon 158, which codes for an enzyme involved in the breakdown of dopamine at the synapse, are believed to contribute to negative and cognitive symptoms in schizophrenia and higher schizotypy scores.[6] According to an older study, platelet monoamine oxidase levels are associated with sociability levels, with low levels occurring in schizotypal personality disorder.[7] 

Research on the etiology of schizotypal personality disorder is limited due to the complexity and multifactorial nature of personality disorders. Biological factors contribute to the development of personality through multiple means, with temperament being a heritable and innate psychobiological characteristic that significantly contributes to personality development.[8][9]

Genetic factors have been attributed as significant contributors to the development of a personality disorder; this was supported by multiple studies that investigated twin, linkage, candidate gene association studies, genome-wide association studies, and polygenic analyses.[8] Individuals with Cluster A personality disorders are more likely to have biological relatives with schizophrenia compared to control groups. The association is stronger for schizotypal personality disorder compared to schizoid personality disorder.[10] Schizotypal personality disorder is more prevalent in individuals with first-degree relatives who have schizotypal personality disorder. Hereditability of schizotypy has been estimated between 30% and 50%. Schizotypal traits are also more often found in relatives of those with schizophrenia.[6] Children with major depressive disorder who develop a personality disorder are more likely to develop schizoid, avoidant, borderline, or schizotypal personality disorders compared to other adult personality disorders.[11] In addition, adult prisoners with a childhood history of institutional care had higher scores on schizotypal traits.[12]

Medical conditions are often associated with personality disorders or alterations in personality, specifically those that may damage neurons. Medical conditions include but are not limited to head trauma, cerebrovascular diseases, cerebral tumors, epilepsy, Huntington's disease, multiple sclerosis, endocrine disorders, heavy metal poisoning, neurosyphilis, and AIDS.[13]

Psychoanalytic factors also contribute to the development of personality disorders. Wilhelm Reich, a psychoanalyst, described character armor as defense mechanisms that develop with personality types to relieve cognitive conflict from internal impulses and interpersonal anxiety. For instance, individuals with schizotypal tendencies have withdrawal defense mechanisms.[14]

Personality is a complex summation of biological, psychological, social, and developmental factors. Each individual's personality is unique, even amongst those diagnosed with a personality disorder. Personality is a pattern of behaviors that an individual uniquely adapts to address constantly changing internal and external stimuli. This broader concept is described as temperament, which has heritable and innate psychobiological characteristics.[8][9] Temperament is further shaped through epigenetic mechanisms, including life experiences such as trauma and socioeconomic conditions, which are referred to as adaptive etiological factors in personality development.[15][16] Temperament traits include harm avoidance, novelty seeking, reward dependence, and persistence.

Harm avoidance involves a bias towards inhibiting behavior that results in punishment or non-reward.[17] Individuals with high harm avoidance often experience fear of uncertainty, social inhibition, shy behavior, and avoidance of danger or the unknown, all of which are characteristics of schizotypal personality disorder.

Novelty seeking describes an inherent desire to initiate novel activities likely to produce a reward signal.[18] Schizotypal personality disorder presents with low novelty seeking, resulting in uninquiring, isolative, and stoical behaviors.

Reward dependence describes the amount of desire to alter behaviors in response to social reward cues.[19] Individuals with schizotypal personality typically have low reward dependence and, as a result, spend most of their time in isolation, with little need for social reward compared to individuals without schizotypal personality disorder.

Persistence describes the ability to maintain behaviors despite frustration, fatigue, and limited reinforcement. Low persistence is consistent with schizotypal personality disorder. Low persistence is associated with indolence, inactivity, and ease of frustration. These individuals rarely strive for higher accomplishments.[19][20]

Epidemiology

The prevalence of schizotypal personality disorder is approximately 3.9% worldwide, with men at higher risk (4.2%) compared to women (3.7%).[21] Cluster A personality disorders are common among individuals experiencing homelessness.[22] Quality measures of the prevalence of schizotypal personality disorder are lacking; therefore, these estimates are limited.[23]

Pathophysiology

There are few investigations of neuroimaging and histopathological findings among Cluster A personality disorders. In a study involving 20 research participants with either schizoid personality disorder or schizotypal personality disorder, structural alterations in the pyramidal pathway were observed compared to controls. Specifically, research participants presented with greater bilateral white matter volume in the superior corona radiata adjacent to motor/premotor regions. The hypothesized conclusion from these findings suggests that greater volume in motor pathways might relate to cognitive disorganization and negative symptoms in the schizophrenia spectrum illnesses.[24] According to magnetic resonance imaging, patients with schizophrenia and schizotypal personality disorder may share similarities in altered gross morphology of the insular cortex, suggesting a vulnerability factor associated with early neurodevelopmental anomalies and increased brain gyrification in diverse cortical regions.[25][26] According to a study, patients with schizotypal personality disorder also had a significantly reduced cortical thickness in the left fusiform and parahippocampal gyri, right medial superior frontal gyrus, right inferior frontal gyrus, and right medial orbitofrontal cortex compared to healthy controls.[27][26][25]

History and Physical

Individuals with schizotypal personality disorder often exhibit a diverse range of clinical features. The individuals may appear odd or eccentric, with magical thinking and odd beliefs. Patients may express paranormal, supernatural, or astrological preoccupations. Patients may appear suspicious, hypervigilant, or paranoid, contributing to having difficulty forming close interpersonal relationships, secondary to concern about how others perceive them. The patient should be assessed for any signs of a formal thought disorder, including disorganization, hallucinations, and profound negative symptoms such as apathy, anhedonia, avolition, and alogia. These symptoms may suggest that the patient's presentation is more consistent with a schizophrenia spectrum disorder rather than schizotypal personality disorder.[1]

Inquiring how a patient with suspected schizotypal personality disorder spends their time and who comprises their social circles is essential. Obtaining a detailed social history may provide insight into how the patient's personality disorder impairs their ability to maintain normal social functioning, including educational struggles and difficulty with maintaining employment or obtaining adequate financial resources. In addition to obtaining a detailed social and personal history from the patient, collateral information is essential in diagnosing personality disorders to augment the clinician's view of how an individual reacts to various circumstances over time.[1]

The following factors should be carefully considered in the psychiatric evaluation, including the mental status examination, of individuals suspected of having schizotypal personality disorder.

• Appearance: May appear unkempt, disheveled, or eccentric appearance with odd attire.
• Behavior: May be inappropriate, stiff, peculiar, socially detached, hypervigilant, suspicious, or overtly paranoid.
• Speech: Speech abnormalities include odd, vague, metaphorical, or stereotyped speech. In addition, individuals tend to have more pauses, slower speech, and less pitch variability.
• Affect: Ranges from constricted to expansive and may be inappropriate to the circumstances.
• Thought Content: May be suspicious or have paranoid ideation with magical thinking, fixation on the supernatural or paranormal, odd beliefs, overvalued ideas, or ideas of reference. Suicidal and homicidal ideation should be assessed at each encounter.
• Thought Process: Ranges from logical and goal-directed to vague and rambling, without actual derailment.
• Perceptions: Likely to describe unusual perceptual experiences, including bodily illusions or sensing that another person is present. These experiences are generally not at the level of overt hallucinations, which suggest a schizophrenia spectrum disorder. 
• Cognition: General cognition and orientation are not impaired in schizotypal personality disorder. However, assessment is necessary to rule out other psychiatric conditions, such as schizophrenia, where cognitive impairment is common.

Evaluation

The diagnosis of a personality disorder depends on longitudinal observation of a patient's behaviors to understand the patient's long-term functioning. Many characteristics of personality disorders overlap with symptoms of acute psychiatric illness.[28] Therefore, personality disorders should generally be diagnosed when there is not a concurrent acute psychiatric condition. An underlying personality disorder may contribute significantly to hospitalizations or relapse of another psychiatric condition, such as a major depressive episode.[29] The diagnosis of schizotypal personality disorder may take several encounters to be firmly established.

Several psychometric assessments can aid in diagnosing schizotypal personality disorder, including:

• The Schizotypal Personality Questionnaire-Brief
• The Personality Diagnostic Questionnaire-4
• The Personality Inventory for DSM-5 (PID-5)
• The Minnesota Multiphasic Personality Inventory (MMPI)

Of these psychometric tools, the Schizotypal Personality Questionnaire-Brief has shown the best internal consistency with a reported alpha coefficient of 0.87.[30]

According to a study, the MMPI was able to cluster schizotypal personality disorder and schizophrenia together accurately more than 90% of the time. However, both clinical entities have significant overlap. The Personality Diagnostic Questionnaire-4 is a good screening tool for personality disorders in general but is not specific to schizotypal personality disorder. In a study, the Personality Inventory for DSM-5 (PID-5) reported a kappa coefficient of 0.5, indicating moderate agreement on the diagnosis of schizotypal personality disorder.[30]

When assessing an individual for schizotypal personality disorder, it is important to consider cultural factors when applying diagnostic criteria. According to the DSM-5-TR, beliefs such as life beyond death, speaking in tongues, voodoo, shamanism, mind reading, sixth sense, evil eye, magical beliefs related to health and illness, and other culture-related issues must be considered when evaluating cognitive and perceptual distortions.

DSM-5-TR Diagnostic Criteria for Schizotypal Personality Disorder

A pervasive pattern of social and interpersonal deficits characterized by acute discomfort with, and reduced capacity for, close relationships, as well as cognitive or perceptual distortions and eccentricities of behavior, typically beginning in early adulthood and present in a variety of contexts, as indicated by 5 (or more) of the following:

• Ideas of reference (excluding delusions of reference).
• Odd beliefs or magical thinking that influence behavior and are inconsistent with subcultural norms, such as superstitious, belief in clairvoyance, telepathy, or sixth sense; in children and adolescents, bizarre fantasies or preoccupations.
• Unusual perceptual experiences, including bodily illusions.
• Odd thinking and speech, such as vague, circumstantial, metaphorical, overelaborate, or stereotyped.
• Suspiciousness or paranoid ideation.
• Inappropriate or constricted affect.
• Behavior or appearance that is odd, eccentric, or peculiar.
• Lack of close friends or confidants other than first-degree relatives.
• Excessive social anxiety does not diminish with familiarity and tends to be associated with paranoid fears rather than negative judgments about self.

Does not occur exclusively during the course of schizophrenia, a bipolar disorder or depressive disorder with psychotic characteristics, another psychotic disorder, or autism spectrum disorder. 

If criteria are met prior to the onset of schizophrenia, premorbid can be added, for example, schizotypal personality disorder (premorbid).

The DSM-5-TR introduced an alternative diagnostic model for personality disorders in the Emerging Measures and Models section. The alternative diagnostic model for personality disorders in the DSM-5-TR is a hybrid dimensional-categorical model that defines personality disorders in terms of impairments in personality functioning and pathological personality traits.[31]

DSM-5-TR Alternative Diagnostic Model for Schizotypal Personality Disorder

The DSM-5-TR alternative diagnostic model for schizotypal personality disorder outlines two main criteria—Criterion A and Criterion B.

Criterion A: This criterion denotes a requirement for moderate or greater impairment in personality functioning. Individuals must demonstrate significant challenges in 2 or more of the following 4 areas.

• Identity: Confused boundaries between self and others; distorted self-concept; emotional expression often not congruent with context or internal experience.
• Self-direction: Unrealistic or incoherent goals; no clear set of internal standards.
• Empathy: Pronounced difficulty understanding the impact of own behaviors on others; frequent misinterpretations of others' motivations and behaviors.
• Intimacy: Marked impairments in developing close relationships associated with mistrust and anxiety.

Criterion B: This criterion outlines 6 pathological personality traits, and diagnosis requires 4 or more of these traits.

• Cognitive and perceptual dysregulation (an aspect of psychoticism): Odd or unusual thought processes; vague, circumstantial, metaphorical, overelaborate, or stereotyped thought or speech; odd sensations in various sensory modalities.
• Unusual beliefs and experiences (an aspect of psychoticism): Thought content and views of reality that are viewed by others as bizarre or idiosyncratic; unusual experiences of reality.
• Eccentricity (an aspect of psychoticism): Odd, unusual, or bizarre behavior or appearance; saying unusual or inappropriate things.
• Restricted affectivity (an aspect of detachment): Little reaction to emotionally arousing situations; constricted emotional experience and expression; indifference or coldness.
• Withdrawal (an aspect of detachment): Preference for being alone to being with others; reticence in social situations; avoidance of social contacts and activity; lack of initiation of social contact.
• Suspiciousness (an aspect of detachment): Expectations of, and heightened sensitivity to, signs of interpersonal ill-intent or harm; doubts about loyalty and fidelity of others; feelings of persecution.

Treatment / Management

Limited evidence-based treatments are available for schizotypal personality disorder, partly due to changes in diagnosis over time and the inclusion of patients with schizotypal personality disorder and comorbid conditions in some studies. There are no medications approved by the Food and Drug Administration; the studies of pharmacotherapy showed that antipsychotic medications were the most commonly used drugs. There is insufficient evidence to recommend any particular psychotherapy treatment for schizotypal personality disorder.[30] Although psychotherapy has shown some promise in helping individuals with this disorder, the existing studies are often underpowered and not randomized. Efficacy has been reported for antidepressants and antipsychotics to help with specific symptoms of schizotypical personality disorder. In particular, second-generation antipsychotics have shown promise in addressing paranoid ideation; however, it is important to note that treatment decisions should be made on a case-by-case basis.[32](A1)

Individuals with schizotypal personality disorder may not recognize their illness and commonly present at the behest of a first-degree relative. Generally, this occurs after maladaptive behaviors have created stress on another rather than internal distress on the part of the individual with schizotypal personality disorder. Therefore, it is essential to assess the goals of treatment in each case of schizotypal personality disorder. As schizotypal personality disorder is unlikely to remit with or without treatment, the focus of treatment may be aimed at reducing interpersonal conflict and stabilizing socioeconomic conditions.[1]

Differential Diagnosis

The differential diagnosis of schizotypal personality disorder is broad. The disorder must be differentiated from schizophrenia, and, as noted in the DSM-5-TR, if the patient proceeds to develop a schizophrenia spectrum disorder, the diagnosis of schizotypal personality disorder must be recorded with the qualifier of premorbid. Schizotypal personality disorder belongs to the Cluster A personality disorders, which are all believed to exist in the psychotic spectrum without formally being psychotic disorders.[1] If a patient meets the criteria for more than 1 personality disorder, all disorders can be diagnosed accordingly. According to the DSM-5-TR, schizotypal personality disorder can be distinguished from other psychiatric disorders as described below.

Delusional disorder, schizophrenia, and mood disorders with psychotic features are all characterized by a period of persistent psychotic symptoms such as delusions and hallucinations. Individuals with schizotypal personality disorder can present with perceptual distortions and ideas of reference, such as believing that an external event was specifically about them. However, they do not have delusions of reference, which are held with absolute conviction.

Schizotypal personality disorder presents with eccentricities and cognitive or perceptual distortions, whereas these symptoms are absent in schizoid personality disorder and paranoid personality disorder.

Schizotypal personality disorder and neurodevelopmental disorders, such as mild autism spectrum disorders or language communication disorders, share deficits in social reciprocity, emotional functioning, and peculiar speech and behaviors. The presence of magical thinking, perceptual abnormalities, and ideas of reference is more consistent with schizotypal personality disorder. Autism spectrum disorder shows an even greater lack of social awareness, emotional reciprocity, and stereotyped behaviors and interests compared to schizotypal personality disorder.

Personality change due to another medical condition and persistent substance use disorders must be distinguished from schizotypal personality disorder. Medical conditions are often associated with personality disorders or changes, specifically including those with pathology that may damage neurons. Medical conditions include, but are not limited to, head trauma, cerebrovascular diseases, cerebral tumors, epilepsy, Huntington's disease, multiple sclerosis, endocrine disorders, heavy metal poisoning, neurosyphilis, and AIDS.[13]

Pertinent Studies and Ongoing Trials

Few studies have been published on schizotypal personality disorder since the DSM-III in 1980. In the new era of DSM-5-TR and the ever-shifting social landscape, detailed case reports and case series that highlight how schizotypal personality disorder manifests in modern clinical practice are needed.

In the DSM-5-TR, personality disorders are grouped into 3 clusters based on shared characteristics, referred to as Cluster A, Cluster B, and Cluster C. Cluster A refers to personality disorders with odd or eccentric characteristics, including paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder.[33] Cluster B refers to personality disorders with dramatic, emotional, or erratic characteristics, including antisocial personality disorder, borderline personality disorder, histrionic personality disorder, and narcissistic personality disorder.[34] Cluster C refers to personality disorders with anxious and fearful characteristics, including avoidant personality disorder, dependent personality disorder, and obsessive-compulsive personality disorder.[35] Despite the historical use of the cluster system, there are limitations when approaching personality disorders in this manner, and the 3 groupings are not consistently validated in the literature.[36]

Despite behavioral patterns that have been classified into syndromes or personality disorders, the uniqueness of each individual remains problematic for diagnosing and researching specific personality disorders.[36] Experts in personality disorders have suggested switching to a dimensional model of personality rather than continuing to use a cluster model. The proposed dimensional models generally describe temperament, utilization of defense mechanisms, and identification of pathological personality traits.[37] To provide an alternative, the DSM-5-TR added a section with a hybrid dimensional-categorical model to address the shortcomings of the current classifications. As evolving research informs clinical guidelines, the paradigm is likely to undergo a shift in the coming decades.

In addition, new notions of schizotypy have emerged, employing a network approach to conceptualize the disorder as a complex dynamic system.[38]

Prognosis

Schizotypal personality disorder has a relatively stable course, and only a few individuals progress to schizophrenia or another psychotic disorder. Individuals with schizotypal personality disorder are less likely to achieve educational goals or employment.[39] Given the difficulties with interpersonal relationships, they are also less likely to form long-term commitments or have children.[40] Women are more likely to exhibit magical thinking and express interest in topics such as the paranormal.[41][42][43] Men are more likely to have severe cognitive deficits.[44] 

Complications

Schizotypal personality disorder can lead to many potential complications, including an increased risk of substance use, self-harm, and hospitalization.[45][46][47] In some cases, patients may progress to a formal thought disorder such as schizophrenia. Other personality disorders may be comorbid with schizotypal personality disorder, most commonly paranoid, schizoid, borderline, and avoidant personality disorders. Substance use disorders are common among personality disorders, but there is limited evidence on which personality disorders pose the most risk for a substance use disorder.[48] Individuals with personality disorders have an increased likelihood of suicide and suicide attempts compared to those without personality disorders, and individuals with schizotypal personality disorder should be screened regularly for suicidal ideation.[49]