Schizotypal+Personality+Disorder

 By Zhouchunyang Xia

=**Introduction** =

Schizotypal personality disorder (SPD) affects 3.3% of the general public, and it is characterized by extreme introversion whereby a need for social isolation is overwhelming; SPD individuals tend to have odd, egocentric, and often superstitious ways of thinking and behaviours. As well, these individuals exhibit a range of cognitive and perceptual deficits.Over the years researchers have looked into the neurobiological basis of these impairments. One such study has found abnormal neural oscillations during a visual working memory task, while many other studies have looked at neuronal tissue loss and cortical grey and white matter reductions through neuroimaging techniques. These studies are done in an effort to identify areas of the brain abnormalities most prominent in SPD individuals. In addition, genetic factors have been studies closely. One such genetic factor underlying susceptibility to SPD in healthy individuals is the single nucleotide polymorphism (SNP) on Zinc finger protein gene //ZNF804A,// in addition to susceptibility to schizophrenia. High genetic heritability show higher risk in individuals with family members of SPD or schizophrenia1. As its name suggests, individuals with schizotypal personality disorder shares many cognitive impairments with schizophrenia patients, however, there is a global lack of hallucinations, delusions, and loss of contact with reality in SPD individuals. This differential characteristic has sparked many researches over the years, and one increasingly robust theory suggests frontal sparing as a protective mechanism. SPD patients show a significantly smaller amount of reduction in the frontal regions, where executive cognitive functions are carried out, compared with schizophrenia patients [3], [5]. Social and environmental factors also play a factor in SPD onset. Prognosis for SPD is very low. Improving social interaction skills have been one focus of cognitive behaviour therapies in SPD individuals. Pharmacological interventions have looked into methods of both enhancing cognitive functions and decreasing associated psychotic symptoms .  toc

**__1. Diagnosis__**

**1.1 Symptoms**
 Individual with Schizotypal Personality Disorder (SPD) is characterized by a need for social isolation. Odd, egocentric, and often superstitious ways of thinking and behaviours are often. A range of cognitive and perceptual deficits are observed in these individuals; two common deficits include impairment in visual stimuli processing and working memory.

//**i. Diagnostic Criteria**//
 SPD falls into the Cluster A of Personality Disorders as defined in the current version of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) published by American Psychology Association. The specific diagnostic criteria are as follows:

 A pervasive pattern of social and interpersonal deficits marked by acute discomfort with, and reduced capacity for, close relationships as well as by cognitive or perceptual distortions and eccentricities of behavior, beginning by early adulthood and present in a variety of contexts as indicated by 5 or more
 *  Ideas of reference (excluding delusions of reference)
 * Odd beliefs or magical thinking that influences behavior and is inconsistent with subcultural norms (e.g. superstition, belief in clairvoyance, telepathy, "sixth sense", or bizarre fantasies or preoccupations)
 * Unusual perceptual experiences, including bodily illusions
 * Odd thinking and speech (e.g. vague, circumstantial, metaphorical, or stereotyped speaking)
 * <span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Suspiciousness or paranoid ideas
 * <span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Lack of close friends or confidants other than first degree relatives
 * <span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Excessive social anxiety that does not diminish with familiarity and tends to be associated with paranoid fears rather than negative judgments about self.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">//**ii.Controversies**//
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Due to the high level of similarity between symptoms of SPD and Schizophrenia, many researchers have categorized SPD under the Schizophrenia spectrum within their studies4. As well, many genetic studies support including SPD in the schizophrenia spectrum, as they share many genetic polymorphisms.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Currently the diagnosis of SPD is only present in DSM. In the International Statistical Classification of Diseases and Related Health Problems (ICD ), this category of symptom is included as a clinical disorder under the Schizophrenia spectrum.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**1.3 Epidemiology**
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Schizotypal personality disorder affects 3.3% of the general public [1].

<span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 110%; text-align: center;">**__2. Correlational Factors__**

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">//**i. Single Nucleotide Polymorphism (SNP) – Zinc finger protein**//
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> The high similarity of symptoms between SPD and schizophrenia makes it a less attractive target for genetic studies. Not many literatures compared the presence and the degree of genetic polymorphisms in SPD individuals.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> A recent study by Yasuda and colleagues expanded on the research of a single nucleotide polymorphism (SNP) on the zinc finger protein to analyze the susceptibility of healthy individuals to schizotypal personality traits [4]. It has been identified through genome-wide association studies (GWAS), follow-up association studies and meta-analyses that a single nucleotide polymorphism (SNP), rs134476, on the Zinc finger protein gene //ZNF804A//is closely linked with susceptibility to Schizophrenia. As well, an increased susceptibility to schizotypal personality traits is found in healthy subjects of the SNP carrier4. This SNP has been linked to both neuronal connections and the decline in cognitive abilities.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Zinc finger protein The ZNF804A gene spans 341 kb consisting of four exons and three introns. It is located on the long arm of chromosome 2, in region 3, band 2.1 [4]. Susceptible individuals carry the T risk allele in the conserved mammalian region4,6. The specific function of this zinc finger protein gene is unknown, but researchers suspect that it is involved in DNA-binding in transcription and interaction with other RNA and proteins in the brain[7]. Certain studies have found higher expression of the ZNF804A gene has been discovered in the frontal cortex of individuals with schizophrenia, indicating connections between this polymorphism and the defects observed in executive cognitive control within these individuals8. However, some controversies still remain, as other studies have found no expressions of this gene in schizophrenic patients9.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">//**ii. Heritability**//
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> A uniform agreement across all genetic studies is that relatives of individuals with Schizophrenia are at high risk for both schizophrenia and SPD. Studies have found as high as an 80% heritability rate 10. Concordance studies involving twins and family members show an almost 10-fold increase in susceptibility in first-degree relatives10.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**2.2 Cortical Gray and White Matter Volume Reductions**
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> The high similarity and overlap in symptoms with schizophrenia has called for much research into the neuroimaging of SPD individuals. Both grey and white matter abnormalities have been studied and compared between schizophrenic patients, SPD individuals, and healthy controls.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Cortical grey matter refers to the neuronal bodies of the neurons. Grey matter reduction indicates an overall decrease in the amount of cells available to function. Past studies in this field of research have yielded mixed results. A study by Kawasaki and colleagues comparing schizophrenic patients and SPD individuals found common grey area reductions in the left medial temporal and inferior frontal regions11. SPD individuals were found to have greater deduction in the insular and the superior temporal regions than schizophrenic patients; however, a significant reduction of grey matter in the orbital-frontal region was found in schizophrenic patients that is very much absent in SPD individuals. This has implications for differentiating symptoms of schizophrenia from SPD, which will be discussed in a following section. Other areas of cortical abnormalities have been indicated in studies on schizophrenic patients, such as reduction s in the dorsolateral prefrontal cortex, superior temporal gjyrus and superior parietal lobule14. Further studies on the brain structure of SPD individuals found abnormalities in the caudate nucleus volume and the cognitive implications are subsequently discussed in the working memory section15.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Cortical white matter refers to the myelinated axonal connections of the neurons. Disruptions and abnormality in white matter indicate some forms of malfunctions in the neuronal communication and information transfer network within one’s brain. A recent study by Hazelett and colleague localized the sources of negative symptoms (i.e. odd speech, behaviours) into a few distinctive areas in the white matter connections within thetemporal lobe and the cingulum 12. This analysis was performed on the fractional anisotropy (FA), which indicates the density and connectivity of white matters, through diffusion imaging. The image of FA differences between SPD subjects and healthy controls across the cerebrum is shown; one can see significant differences within the temporal lobe and the cingulum.

=<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**2.3 Cognitive Defects in SPD Individuals:** =

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">//**i. Working Memory Processing**//
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Due to the cortical abnormalities, SPD patients experience varying degrees of cognitive defects. Working Memory Processing is one of such areas. A correlation has been established between the volume of the caudate nucleus and the efficiency on working memory among SPD individuals15. The caudate nucleus (see figure) is part of the striatal nuclei important in relaying sensory information from the cortex (primarily the frontal cortex) to the basal ganglia. A reduced volume in the caudate nucleus indicates interference with the information relay network, which may result in defects in the process speed and retention of information. Consequently, SPD individuals show impairment working memory processing and other cognitive abilities. As Levitt and colleagues have shown, SPD individuals performed much poorer on spatial and verbal fluency working memory tasks (see figures).

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">//**ii. Sensory Processing**//
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> In SPD individuals, sensory processing defects are often linked with working memory defects. Research indicates that the source of both impairments is interrelated. EEG studies have shown abnormal brain oscillations consistent with disruptions in cortical connectivity during memory processing; as well it indicated a dysfunctional top-down sensory processing with SPD17. Top-down sensory processing refers to perceiving a large concept first and then breaking it down into details.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Studies using event-related potentials have found high similarity between schizophrenic patients and high SPD individuals in terms of defect in the early visual processing of the magnocellular visual pathway18. This pathway is suggested to be involved in spatial orientation, motion detection, and stimulus perception. However, despite the similarity, SPD individuals were able to compensate for the defect through a mechanism that is not yet known18.

<span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 110%; text-align: center;">**__3. Social Risk Factors__** <span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Studies have found that the duration of separation from mother in the first two years of life predicted elevated SPD symptoms (see figure)19. However, the finding is very limited, as the sample sizes are restricted with the low prevalence of SPD in the general population.

<span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 110%; text-align: center;">**__4. Differentiating with Schizophrenia__**

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**4.1 Florid psychosis and frontal lobe sparing**
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> A major distinction between schizophrenia and SPD is the absence of florid psychosis in SPD indiciduals[3,11]. Florid psychosis is defined as the hallucination and delusions present in schizophrenic patients, which is largely absent in individuals with SPD. A review by Hazlett and colleagues looking at neuroimaging data on the white matter connectivity of SPD individuals compared with schizophrenic individuals found that SPD individuals have fewer abnormalities in the frontal region3. This suggests that to a certain degree, frontal sparing serves as a neuroprotective factor from florid psychosis in SPD individuals. Furthermore, less grey matter reduction is observed in the frontal region of SPD individuals compared to schizophrenia patients11.

<span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 110%; text-align: center;">**__5. Therapeutic methods and prognosis__**

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**5.1 Pharmacological treatment**
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Currently there are no medications designed specifically to tread SPD, although drugs targeting specific symptoms may be prescribed. A proposed pharmacological drug for improving working memory in SPD individuals is Guanfacine10. Guanfacine is an alpha 2A receptor agonist that targets the post-synaptic G-protein coupled receptor in the prefrontal cortex. Preliminary research indicates a positive effect on symptoms that is greater than placebo.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Nonetheless, with any type of pharmacological treatment, there runs the risk of becoming resistant and /or addicted to the prescribed drug.

<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">**5.2 Cognitive behavioral therapy**
<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Limited researches are present on the effect of cognitive behavioral therapy on SPD individuals, however, one can infer from studies in schizophrenic patients. The cognitive aspect of the therapy involves teaching the patients correct ways of dealing with their odd patterns of thought. The behavioral aspect aims to teach SPD individuals self-competency skills and social skills, so that they may be able to function independently in societal settings. Studies on schizophrenia shows that long term cognitive behavioural therapy coupled with pharmacological treatment may improve the prognosis 21.

<span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">**References** <span style="color: black; font-family: 'Times New Roman',Times,serif; font-size: 110%;">

**__<span style="font-family: 'Times New Roman',serif; font-size: 12pt;">References __**<span style="font-family: 'Times New Roman',serif; font-size: 12pt;">:
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