Alterations in facial expressions in individuals at risk for psychosis: a facial electromyography approach using emotionally evocative film clips.

BACKGROUND: Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis. METHODS: This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms. RESULTS: Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores. CONCLUSIONS: Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development.

Neurodevelopmental vulnerability to psychosis: developmentally-based methods enable detection of early life inhibitory control deficits that predict psychotic-like experiences at the transition to adolescence.

BACKGROUND: Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention. METHODS: Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3-5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; 'tween'; ages 9-12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8-11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control. RESULTS: Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F(1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4-9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F(2,202) = 5.618, p = 0.004, and externalizing symptoms, F(2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F(1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms. CONCLUSIONS: Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention.

Postural sway and neurocognition in individuals meeting criteria for a clinical high-risk syndrome.

Neurocognitive deficits are implicated in individuals that meet criteria for a clinical high-risk (CHR) syndrome. Evidence in patients with schizophrenia suggests that cerebellar dysfunction may underlie neurocognitive deficits. However, little research has examined if similar associations are present in those meeting CHR criteria. This study examined associations between the MATRICS cognitive battery, postural sway (an index of cerebellar functioning), and SIPS-RC psychosis risk scores in a CHR sample (N = 66). Poorer working memory and processing speed were associated with less postural control. Consistent with the cognitive dysmetria theory of schizophrenia, neurocognitive deficits are associated with cerebellar dysfunction in this critical population.

Timing dysfunction and cerebellar resting state functional connectivity abnormalities in youth at clinical high-risk for psychosis.

BACKGROUND: Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms. METHODS: A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified. RESULTS: Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months. CONCLUSIONS: Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.

Translating RDoC to Real-World Impact in Developmental Psychopathology: A Neurodevelopmental Framework for Application of Mental Health Risk Calculators.

The National Institute of Mental Health Research Domain Criteria's (RDoC) has prompted a paradigm shift from categorical psychiatric disorders to considering multiple levels of vulnerability for probabilistic risk of disorder. However, the lack of neurodevelopmentally-based tools for clinical decision-making has limited RDoC's real-world impact. Integration with developmental psychopathology principles and statistical methods actualize the clinical implementation of RDoC to inform neurodevelopmental risk. In this conceptual paper, we introduce the probabilistic mental health risk calculator as an innovation for such translation and lay out a research agenda for generating an RDoC- and developmentally-informed paradigm that could be applied to predict a range of developmental psychopathologies from early childhood to young adulthood. We discuss methods that weigh the incremental utility for prediction based on intensity and burden of assessment, the addition of developmental change patterns, considerations for assessing outcomes, and integrative data approaches. Throughout, we illustrate the risk calculator approach with different neurodevelopmental pathways and phenotypes. Finally, we discuss real-world implementation of these methods for improving early identification and prevention of developmental psychopathology. We propose that mental health risk calculators can build a needed bridge between RDoC's multiple units of analysis and developmental science.

Postural Control and Verbal and Visual Working Memory Correlates in Nonclinical Psychosis.

INTRODUCTION: Motor and cognitive abnormalities are well documented in psychosis spectrum disorders. Evidence suggests these deficits could be pronounced because of disruptions in the cerebellar-thalamic-cortical-cerebellar (CTCC) circuit, a network thought to be heavily implicated in motor and higher cognitive functioning. Although significant research has been done on this topic in individuals with schizophrenia and those at a clinical high risk for psychosis, much less is known about deficits at the lower end of the spectrum. METHODS: In this study, we extended the understanding of motor abnormalities across the psychosis continuum by examining postural sway deficits in the nonclinical psychosis (NCP) population. Furthermore, we linked these deficits to verbal and visual working memory. High-NCP (n = 37) and low-NCP control (n = 31) participants completed an instrumental balance task, highly sensitive to subtle variations in postural sway, along with a brief working memory battery. RESULTS: We found that high-NCP participants presented with increased postural sway area (i.e., worse postural control) relative to low-NCP controls on a difficult condition (with limited proprioceptive cues), but not on an easier condition. Furthermore, results indicated that the sway area was correlated with poorer performance on working memory tasks in the high-NCP group. CONCLUSION: These findings suggest that CTCC circuit abnormalities are present across the lower end of the psychosis spectrum and that they may be contributing to a range of motor and cognitive behaviors seen in the population. However, evidence suggests that the signs are subtle, and that sensitive assessment devices and challenging conditions may be necessary for detection.

Detecting motor slowing in clinical high risk for psychosis in a computerized finger tapping model.

Finger tapping is sensitive to motor slowing and emerging symptoms in individuals at clinical high risk for psychosis (CHR). A sensitive, computerized finger tapping task would be beneficial in early psychosis screening batteries. The study included 41 CHR and 32 healthy volunteers, who completed a computerized finger tapping task and clinical interviews. This computerized finger tapping task was sensitive to slowing in the CHR group compared to healthy volunteers, and as expected negative but not positive symptoms related to motor slowing. Computerized finger tapping tasks may be an easily dispersible tool for early symptom detection battery relevant to emerging negative symptoms.

Early childhood social communication deficits in youth at clinical high-risk for psychosis: Associations with functioning and risk.

Effective social functioning requires a broad range of social communication skills that are impaired in psychosis populations. However, little is known about early childhood (4- to 5-year period) social communication during the premorbid (pre-illness) stage of psychosis. The present study utilized retrospective parent reports to examine total early childhood social communication deficits, as well as deficits in two distinct domains, reciprocal social interaction (social smiling/eye gaze) and communication (social chat/gesture), in youth at clinical high-risk (CHR) for psychosis (ages 13-21; 37.2% female). Furthermore, associations between early childhood social communication and CHR youth's current functioning (social, academic/work), symptoms (positive/negative), and risk for conversion to psychosis were examined. Compared to healthy controls, CHR individuals had greater deficits in total and communication-specific early childhood social communication. Early childhood total, communication, and reciprocal social interaction deficits were associated with worse current functioning and greater current negative symptom severity (amotivation/anhedonia) in CHR youth. Early childhood total and reciprocal social interaction deficits were also associated with increased risk for conversion. These findings inform the field's understanding of the etiology and pathophysiology of psychosis by extending the current developmental literature on premorbid deficits in psychosis populations to specific domains of social behavior in a critical developmental period.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Enthusiasm for cancer screening in Great Britain: a general population survey.

BACKGROUND: With growing concerns about risk of harm from cancer screening, particularly from overdiagnosis, this study aimed to assess public attitudes to cancer screening in Great Britain. METHODS: We used a population-based survey to assess attitudes to cancer screening, screening history and demographic characteristics, in men and women aged 50-80 years. Data were collected using face-to-face computer-assisted interviews in 2012. RESULTS: In our sample of 2024, attitudes to cancer screening were overwhelmingly positive with almost 90% believing that screening is 'almost always a good idea' and 49% saying they would be tested for cancer even if it was untreatable. Attitudes were particularly positive among those who had previously taken part in breast or colorectal screening. CONCLUSIONS: Our findings suggest that attitudes to cancer screening are very positive in Great Britain. Widespread enthusiasm for cancer screening may hamper attempts to encourage a greater appreciation of the limitations and potential harms of screening.

A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative.

Steroid receptors have been around in the field of breast cancer for decades now. Still, controversy remains on how best to report steroid receptors. In this review, we will convince the reader why benefits outweigh pitfalls, when reporting steroid receptors in a quantitative rather than qualitative way. Summarizing decades of research in this field, we will explore the evidence why quantitative reporting is superior in all settings (neoadjuvant, adjuvant and metastatic settings). Furthermore, we will also summarize different staining methods, definitions and pitfalls that have shown to be important points of discussion in earlier debates. Although the molecular unraveling of breast cancer in the past decade has revolutionized the way we think about breast cancer, we should not easily abandon the classical pathological variables such as steroid receptors in favor of molecular tools.

Clinical high risk for psychosis syndrome is associated with reduced neural responding to unpleasant images.

Deficits in emotion processing are core features of psychotic disorders. Electrophysiology research in schizophrenia suggests deficits in sustained engagement with emotional content (indexed by the late positive potential [LPP]) may contribute to emotion processing impairments. Despite similar behavioral emotion processing dysfunction in those at clinical high risk (CHR) for psychosis, limited research has examined neural mechanisms of impaired emotion processing in the high-risk period, where research can inform risk models. To examine mechanisms of emotion processing deficits in those at CHR for psychosis, the present study used a passive viewing task to elicit the LPP in response to emotionally engaging and neutral stimuli in 28 CHR and 32 control participants (60% female). Relative to controls, CHR participants showed reduced LPP amplitude when viewing unpleasant images (d = 0.75, p = .005) but similar LPP amplitude in response to both neutral (d = 0.35, p = .19) and pleasant images (d = 0.31, p = .24). This pattern suggests that individuals at CHR for psychosis exhibit a deficit in sustained engagement with unpleasant stimuli. Clinical and trait questionnaires were administered to examine potential exploratory explanations for group differences in LPP amplitude. Consistent with evidence suggesting LPP amplitude reflects engagement of approach/avoidance motivational systems, greater LPP amplitude was associated with greater trait-level behavioral avoidance in control participants (r = .42, p = .032) but not CHR participants (r = -.21, p = .40). Together, the present research is consistent with LPP studies in psychosis and implicates reduced sustained engagement with emotional content in the high-risk period. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Differentiating kinds of systemic stressors with relation to psychotic-like experiences in late childhood and early adolescence: the stimulation, discrepancy, and deprivation model of psychosis.

INTRODUCTION: Conceptualizations that distinguish systems-level stress exposures are lacking; the Stimulation (lack of safety and high attentional demands), Discrepancy (social exclusion and lack of belonging), and Deprivation (lack of environmental enrichment) (SDD) theory of psychosis and stressors occurring at the systems-level has not been directly tested. METHODS: Exploratory factor analysis was conducted on 3,207 youth, and associations with psychotic-like experiences (PLEs) were explored. RESULTS: Though model fit was suboptimal, five factors were defined, and four were consistent with the SDD theory, and related to PLEs. Objective and subjective/self-report exposures for deprivation showed significantly stronger PLE associations compared to discrepancy and objective stimulation factors. Objective and subjective/self-report measures converged overall, though self-report stimulation exhibited a significantly stronger association with PLEs compared to objective stimulation. DISCUSSION: Considering distinct system-level exposures could help clarify putative mechanisms and psychosis vulnerability. The preliminary approach potentially informs health policy efforts aimed at psychopathology prevention and intervention.

An Event-Related Potential Investigation of Early Visual Processing Deficits During Face Perception in Youth at Clinical High Risk for Psychosis.

Impairments in early visual face perception are well documented in patients with schizophrenia. Specifically, event-related potential (ERP) research in patients with schizophrenia has demonstrated deficits in early sensory processing of stimulus properties (P1 component) and the structural encoding of faces (N170 component). However, it is not well understood if similar impairments are present in individuals at clinical high risk (CHR) for psychosis (ie, those in the putative prodromal stage of the illness). Thus, it is unknown if face perception deficits are the result of illness onset or are present in the high-risk period for the illness. The present study used the ERP technique to examine neural activation when viewing facial emotion expressions and objects in 44 CHR and 47 control adolescents and young adults (N = 91). P1 amplitude was similar across groups, indicating that early sensory processing impairments did not substantially contribute to face perception deficits in CHR youth. CHR youth exhibited reduced N170 amplitude compared to controls when viewing faces but not objects, implicating a specific deficit in the structural encoding of faces rather than a general perceptual deficit. Further, whereas controls demonstrated the expected face-selective N170 effect (ie, larger amplitude for faces than objects), CHR youth did not, which suggests that facial emotion expressions do not elicit the expected preferential perceptual processing for critical social information in individuals at CHR for psychosis. Together, these findings provide valuable information regarding the specific impairments contributing to face perception deficits in the high-risk period where treatment stands to aid in preventing illness progression.

Neural mechanisms of motor dysfunction in individuals at clinical high-risk for psychosis: Evidence for impairments in motor activation.

Motor abnormalities are a core feature of psychotic disorders observed from the premorbid period through chronic illness, suggesting motor dysfunction may reflect the pathophysiology of psychosis. Electrophysiology research in schizophrenia suggests impaired motor activation and preparation may underlie these motor abnormalities. Despite behavioral studies suggesting similar motor dysfunction in those at clinical high-risk (CHR) for psychosis, there have been no studies examining neural mechanisms of motor dysfunction in the CHR period, where research can inform pathophysiological and risk models. The present study used the lateralized readiness potential (LRP), an event-related potential index of motor activation and preparation, to examine mechanisms of motor dysfunction in 42 CHR and 41 control participants (N = 83, 56% female). Response competition was manipulated to determine whether deficits are secondary to cognitive control impairments or reflect primary motor deficits. Behaviorally, CHR participants exhibited overall slower responses than controls. Further, relative to controls, CHR participants showed reduced activation of correct but not incorrect responses, reflected in blunted LRP amplitude under weak response competition and no difference in amplitude associated with the incorrect response under strong response competition. This pattern of results suggests individuals at CHR for psychosis exhibit primary motor deficits in activating and preparing behavioral responses and are contrary to a deficit in cognitive control. Further, blunted LRP amplitude was associated with worsening of negative symptoms at 12-month follow-up. Together, these findings are consistent with LRP studies in psychosis and implicate motor activation deficits as potential mechanisms of motor dysfunction in the high-risk period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Abnormal Gesture Perception and Clinical High-Risk for Psychosis.

Individuals diagnosed with psychotic disorders exhibit abnormalities in the perception of expressive behaviors, which are linked to symptoms and visual information processing domains. Specifically, literature suggests these groups have difficulties perceiving gestures that accompany speech. While our understanding of gesture perception in psychotic disorders is growing, gesture perception abnormalities and clues about potential causes and consequences among individuals meeting criteria for a clinical high-risk (CHR) syndrome is limited. Presently, 29 individuals with a CHR syndrome and 32 healthy controls completed an eye-tracking gesture perception paradigm. In this task, participants viewed an actor using abstract and literal gestures while presenting a story and eye gaze data (eg, fixation counts and total fixation time) was collected. Furthermore, relationships between fixation variables and both symptoms (positive, negative, anxiety, and depression) and measures of visual information processing (working memory and attention) were examined. Findings revealed that the CHR group gazed at abstract gestures fewer times than the control group. When individuals in the CHR group did gaze at abstract gestures, on average, they spent significantly less time fixating compared to controls. Furthermore, reduced fixation (ie, count and time) was related to depression and slower response time on an attentional task. While a similar pattern of group differences in the same direction appeared for literal gestures, the effect was not significant. These data highlight the importance of integrating gesture perception abnormalities into vulnerability models of psychosis and inform the development of targeted treatments for social communicative deficits.