Investigating the role of alexithymia on the empathic deficits found in schizotypy and autism spectrum traits.

Alexithymia, the inability to identify and describe one's emotional experience, is elevated in many clinical populations, and related to poor interpersonal functioning. Alexithymia is also associated with empathic deficits in individuals with autism spectrum disorders. Accordingly, a better understanding of alexithymia could elucidate the nature of social-cognitive deficits transdiagnostically. We investigated alexithymia and components of empathy in relation to schizotypal and autism spectrum traits in healthy college students. Specifically, we examined higher-order components of empathic processing that involve perspective taking and other-oriented concern, which are reduced in alexithymia. Higher-order empathic processing was inversely correlated with both schizotypal and autism spectrum traits. Bootstrapping techniques revealed that alexithymia had a significant indirect effect on the relationship between higher-order empathy and these personality traits; thus, alexithymia contributes uniquely to their relationship. These findings suggest alexithymia represents one possible mechanism for the development of empathic deficits in these populations. These results are consistent with the perspective that awareness of one's own emotional state may predicate a successful empathic response to another's. This work highlights the importance of a consideration of alexithymia in elucidating the nature of empathic deficits in various clinical populations, and points to a potential point of social intervention.

A VISION Substudy of Reader Agreement on 68Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for 177Lu-PSMA-617 Radioligand Therapy.

[ 68Ga]Ga-PSMA-11 ( 68Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, 68Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of 68Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study. Methods: In VISION, 68Ga-PSMA-11 PET/CT scans were centrally read as inclusion cases if they had at least 1 PSMA-positive lesion and no PSMA-negative lesions that fulfilled the exclusion criteria. In this substudy, 125 PET/CT scans (75 inclusion and 50 exclusion cases) were randomly selected from VISION and retrospectively assessed by 3 independent central readers. A random subset of 20 cases (12 inclusion and 8 exclusion cases) was recoded for assessment of intrareader reproducibility. Classification of cases as inclusion or exclusion cases was based on the VISION read criteria. Overall interreader variability was assessed by Fleiss κ-statistics, and pairwise variability and intrareader reproducibility were assessed by Cohen κ-statistics. Results: For interreader variability, the readers agreed on 77% of cases (overall average agreement rate, 0.85; Fleiss κ, 0.60 [95% CI, 0.50-0.70]). The pairwise agreement rate was 0.82, 0.88, and 0.84, and the corresponding Cohen κ was 0.54 (95% CI, 0.38-0.71), 0.67 (95% CI, 0.52-0.83), and 0.59 (95% CI, 0.43-0.75), respectively. For intrareader reproducibility, the agreement rate was 0.90, 0.90, and 0.95, and the corresponding Cohen κ was 0.78 (95% CI, 0.49-0.99), 0.76 (95% CI, 0.46-0.99), and 0.89 (95% CI, 0.67-0.99), respectively. The number of actual VISION inclusion cases out of the total number of cases scored as inclusion in this substudy was 71 of 93 (agreement rate, 0.76; 95% CI, 0.66-0.85) for reader 1, 70 of 88 (0.80; 0.70-0.87) for reader 2, and 73 of 96 (0.76; 0.66-0.84) for reader 3. All readers agreed on 66 of 75 VISION inclusion cases. Conclusion: Moderate-to-substantial interreader agreement and substantial-to-almost perfect intrareader reproducibility for 68Ga-PSMA-11 PET/CT scan assessment using the VISION read criteria were observed. The read rules applied in VISION can be readily learned and demonstrate good reproducibility.

Increased plasticity of bodily self-experience in individuals who may carry latent liability for schizophrenia.

Self-disturbances such as altered perception of one's own body boundary are central to the lived-in experience of schizophrenia. Bodily self-disturbances are also prevalent in healthy individuals who may carry latent liability for schizophrenia. Much of the research on self-disturbances rely on clinical interviews but these experiences are often difficult to verbalize, conceptualize and quantify. Furthermore, experimental evidence for plasticity of bodily self-experience in the schizophrenia-spectrum is scarce. We sought to quantify body boundary experience in healthy young adults who might be at an increased risk for schizophrenia with a multisensory paradigm known as the Pinocchio Illusion (PI) task that engenders the feeling that one's nose is changing, and has previously been used to demonstrate increased plasticity of bodily self-boundary in schizophrenia. 62 college students participated in the PI task that assessed bodily self-disturbances, and a tactile discrimination task. We administered the Prodromal Questionnaire Brief (PQ-B) and the Schizotypal Personality Questionnaire (SPQ) to assess latent liability for schizophrenia. We found that PI was enhanced in individuals with elevated PQ-B scores but their tactile sensitivity was intact. PI was associated with the positive syndrome of schizotypy, but not with negative or disorganized factors. Increased PQ-B and SPQ scores were associated with loneliness. To conclude, these results highlight the importance of bodily self-disturbances in the broader context of the schizophrenia spectrum.

Bodily self-disturbance in schizophrenia-spectrum populations: Introducing the Benson et al. Body Disturbances Inventory (B-BODI).

Anomalous or weakened sense of self was central to early theories of schizophrenia. Recent studies have also documented disturbances in body ownership and increased susceptibility for dissociative experiences, such as the out-of-body experience in individuals with schizophrenia, but further research is necessary to clarify components of bodily self-disturbances in the schizophrenia spectrum, and the stability of these experiences over time. With respect to methodology, self-disturbances research in schizophrenia tends to rely exclusively on verbal self-report questionnaires and interviews. Given that individuals with schizophrenia suffer from language and communication difficulties, verbal self-report measures may be insufficient. To bridge this gap, we have developed a new picture-based instrument, the Benson et al. Body Disturbances Inventory (B-BODI), designed to quantify bodily self-disturbances with respect to the frequency and vividness of these experiences, as well as the degree of distress associated with them. Drawings that depicted different aspects of aberrant bodily self-experiences were presented with accompanying captions. Participants were asked to indicate the frequency, vividness, and distressfulness of the experience captured by the picture using a 5-point scale. Individuals with schizophrenia, older healthy controls, and college students participated in two alternative versions of the B-BODI. Participants were also asked to complete a battery of established questionnaires that probed psychosis proneness and a range of self, body, and perceptual aberrations. The results suggest that the B-BODI is a useful tool that accurately captures bodily self-disturbances and has the potential to predict psychosis risk in healthy young individuals. Furthermore, anomalous self-disturbances seem to be relatively stable across time in individuals with chronic schizophrenia.

Development of Targeted Therapies Based on Gene Modification.

With the advent of next-generation sequencing (NGS) and the demand for a personalized healthcare system, the fields of precision medicine and gene therapy are advancing in new directions. There is a push to identify genes that contribute to disease development, either alone or in conjunction with other genes or environmental factors, and then design targeted therapies based on this knowledge, rather than the traditional approach of treating generalized symptoms with pharmaceuticals in a one-size-fits-all manner. Identification of genes that contribute to disease pathogenesis and progression is critical for the maturation of the precision medicine field. Concomitant with a better understanding of disease pathology, precision medicine approaches can be adopted with greater confidence and are expected to lead to a new standard for clinical practice. In this chapter, we provide a brief introduction to precision medicine, discuss the importance of identifying genes and genetic variants that contribute to disease development and progression, offer examples of approaches that can be applied to treat specific diseases, and present some of the current challenges and limitations of precision medicine.

Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia.

Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.

Exceptional visuospatial imagery in schizophrenia; implications for madness and creativity.

Biographical and historical accounts suggest a link between scientific creativity and schizophrenia. Longitudinal studies of gifted children indicate that visuospatial imagery plays a pivotal role in exceptional achievements in science and mathematics. We asked whether visuospatial imagery is enhanced in individuals with schizophrenia (SZ). We compared SZ and matched healthy controls (HC) on five visuospatial tasks tapping parietal and frontoparietal functions. Two aspects of visuospatial transformation, spatial location and mental imagery manipulation were examined with Paper Folding Test (PFT) and jigsaw puzzle task (JPT), respectively. Visuospatial intelligence was assessed with Ravens Progressive Matrices, which is associated with frontoparietal network activity. Hemispatial inattention implicating parietal function was assessed with line bisection (LB) task. Mediated by prefrontal cortex, spatial delayed response task (DRT) was used to index working memory maintenance, which was impaired in SZ compared to HC. In contrast, SZ showed intact visuospatial intelligence and transformation of location. Further, SZ performed significantly better than HC on JPT indicating enhanced mental imagery manipulation. Spatial working memory (SWM) maintenance and mental imagery manipulation were strongly associated in HC but dissociated in SZ. Thus, we observed enhanced mental imagery manipulation in SZ but the dissociation of mental imagery from working memory suggests a disrupted frontoparietal network. Finally, while HC showed the expected leftward pseudoneglect, SZ showed increased rightward LB bias implicating left hemispatial inattention and impaired right parietal control of spatial attention. The current results chart a unique profile of impaired, spared and enhanced parietal-mediated visuospatial functions implicating parietal abnormalities as a biobehavioral marker for SZ. We discuss these results in relation to creative cognition.

Psychosis-proneness and the rubber hand illusion of body ownership.

Psychosis and psychosis-proneness are associated with abnormalities in subjective experience of the self, including distortions in bodily experience that are difficult to study experimentally due to lack of structured methods. In 55 healthy adults, we assessed the relationship between self-reported psychosis-like characteristics and susceptibility to the rubber hand illusion of body ownership. In this illusion, a participant sees a rubber hand being stroked by a brush at the same time that they feel a brush stroking their own hand. In some individuals, this creates the bodily sense that the rubber hand is their own hand. Individual differences in positive (but not negative) psychosis-like characteristics predicted differences in susceptibility to experiencing the rubber hand illusion. This relationship was specific to the subjective experience of rubber hand ownership, and not other unusual experiences or sensations, and absent when a small delay was introduced between seeing and feeling the brush stroke. This indicates that individual differences in susceptibility are related to visual-tactile integration and cannot be explained by differences in the tendency to endorse unusual experiences. Our findings suggest that susceptibility to body representation distortion by sensory information may be related or contribute to the development of psychosis and positive psychosis-like characteristics.