The Intricate Relationship between Psychotic-Like Experiences and Associated Subclinical Symptoms in Healthy Individuals

The interplay between subclinical psychotic, negative, and affective symptoms has gained increased attention regarding the etiology of psychosis spectrum and other mental disorders. Importantly, research has tended to not differentiate between different subtypes of psychotic-like experiences (PLE) although they may not have the same significance for mental health. In order to gain information on the subclinical interplay between specific PLE and other symptoms as well as the significance of PLE for mental health, we investigated their specific associations in 206 healthy individuals (20–60 years, 73 females) using correlational and linear regression analyses. PLE were assessed with the Magical Ideation Questionnaire, the revised Exceptional Experiences Questionnaire, and subscales of the Schizotypal Personality Questionnaire (SPQ). The revised Symptom Checklist 90, the SPQ, and the Physical Anhedonia Scale were used to measure subclinical negative symptoms, affective symptoms, and other symptoms such as, emotional instability. As hypothesized, we found that (1) most affective symptoms and all other subclinical symptoms correlated positively with all PLE, whereas we found only partial associations between negative symptoms and PLE. Notably, (2) magical ideation and paranormal beliefs correlated negatively with physical anhedonia. In the regression analyses we found (3) similar patterns of specific positive associations between PLE and other subclinical symptoms: Suspiciousness was a specific predictor of negative-like symptoms, whereas ideas of reference, unusual perceptual experiences, and dissociative anomalous perceptions specifically predicted anxiety symptoms. Interestingly, (4) ideas of reference negatively predicted physical anhedonia. Similarly, paranormal beliefs were negatively associated with constricted affect. Moreover, odd beliefs were a negative predictor of depression, emotional instability, and unspecific symptoms. Our findings indicated that subtypes of PLE are differentially implicated in psychological functioning and should therefore not be categorized homogeneously. Moreover, paranormal beliefs, odd beliefs, and partly ideas of reference might also contribute to subjective well being in healthy individuals. Our results might serve as a starting point for longitudinal studies investigating the interplay of subtypes of subclinical symptoms along a psychopathological trajectory leading to mental disorders. Importantly, this research might help to improve therapeutic strategies for psychosis prevention

Psychotic-like experiences at the healthy end of the psychosis continuum

There is increasing evidence pointing toward a continuous distribution of psychotic symptoms and accompanying factors between subclinical and clinical populations. However, for the construction of continuum models, a more detailed knowledge of different types of psychotic-like experiences (PLE) and their associations with distress, functional impairment, and demographic variables is needed. We investigated PLE in a sample of healthy adults (N = 206) incorporating the recently developed revised Exceptional Experiences Questionnaire (PAGE-R). For the first time, the PAGE-R was cross validated with PLE, disorganized-, and negative-like symptoms [Schizotypal Personality Questionnaire (SPQ), Physical Anhedonia Scale (PAS)]. We subjected the PAGE-R to exploratory factor analyses and examined the resulting subtypes of EE for specific associations with contextual factors, valence ratings, socio-demographic variables, and general psychological burden (Revised Symptom-Checklist-90). Correlational cross-validation suggested that the PAGE-R measures facets of PLE. Importantly, we (1) identified three types of exceptional experiences (EE): Odd beliefs, dissociative anomalous perceptions, and hallucinatory anomalous perceptions. Further, the results suggested that even in healthy individuals (2) PLE and EE are indicative of reduced functioning, as reflected by increased psychological burden and lower educational achievement. Moreover, (3) similar sex-differences might exist as in psychotic patients with women reporting more positive-like symptoms and EE but less disorganized-like symptoms than men. Importantly, (4) EE might be differentially implicated in psychological functioning. We suggest that the PAGE-R holds the potential to complement the current assessment of sub-clinical psychosis. However, whereas our results might point toward a continuity of psychotic symptoms with EE and normal experiences, they require replication in larger samples as well as equivalence testing across the psychosis continuum. Future analyses incorporating the PAGE-R might shed more light onto mechanisms that are implicated in the progress or resilience toward clinical illness

Cortical Volume Differences in Subjects at Risk for Psychosis Are Driven by Surface Area

In subjects at risk for psychosis, the studies on gray matter volume (GMV) predominantly reported volume loss compared with healthy controls (CON). However, other important morphological measurements such as cortical surface area (CSA) and cortical thickness (CT) were not systematically compared. So far, samples mostly comprised subjects at genetic risk or at clinical risk fulfilling an ultra-high risk (UHR) criterion. No studies comparing UHR subjects with at-risk subjects showing only basic symptoms (BS) investigated the differences in CSA or CT. Therefore, we aimed to unravel the contribution of the 2 morphometrical measures constituting the cortical volume (CV) and to test whether these groups inhere different morphometric features. We conducted a surface-based morphometric analysis in 34 CON, 46 BS, and 39 UHR to examine between-group differences in CV, CSA, and CT vertex-wise across the whole cortex. Compared with BS and CON, UHR individuals presented increased CV in frontal and parietal regions, which was driven by larger CSA. These groups did not differ in CT. Yet, at-risk subjects who later developed schizophrenia showed thinning in the occipital cortex. Furthermore, BS presented increased CSA compared with CON. Our results suggest that volumetric differences in UHR subjects are driven by CSA while CV loss in converters seems to be based on cortical thinning. We attribute the larger CSA in UHR to aberrant pruning representing a vulnerability to develop psychotic symptoms reflected in different levels of vulnerability for BS and UHR, and cortical thinning to a presumably stress-related cortical decomposition

Triple Network Model Dynamically Revisited: Lower Salience Network State Switching in Pre-psychosis

Emerging evidence has attributed altered network coordination between the default mode, central executive, and salience networks (DMN/CEN/SAL) to disturbances seen in schizophrenia, but little is known for at-risk psychosis stages. Moreover, pinpointing impairments in specific network-to-network interactions, although essential to resolve possibly distinct harbingers of conversion to clinically diagnosed schizophrenia, remains particularly challenging. We addressed this by a dynamic approach to functional connectivity, where right anterior insula brain interactions were examined through co-activation pattern (CAP) analysis. We utilized resting-state fMRI in 19 subjects suffering from subthreshold delusions and hallucinations (UHR), 28 at-risk for psychosis with basic symptoms describing only self-experienced subclinical disturbances (BS), and 29 healthy controls (CTR) matched for age, gender, handedness, and intelligence. We extracted the most recurring CAPs, compared their relative occurrence and average dwell time to probe their temporal expression, and quantified occurrence balance to assess the putative loss of competing relationships. Our findings substantiate the pivotal role of the right anterior insula in governing CEN-to-DMN transitions, which appear dysfunctional prior to the onset of psychosis, especially when first attenuated psychotic symptoms occur. In UHR subjects, it is longer active in concert with the DMN and there is a loss of competition between a SAL/DMN state, and a state with insula/CEN activation paralleled by DMN deactivation. These features suggest that abnormal network switching disrupts one's capacity to distinguish between the internal world and external environment, which is accompanied by inflexibility and an excessive awareness to internal processes reflected by prolonged expression of the right anterior insula-default mode co-activation pattern

Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study

Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience

Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study

Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience.ISSN:0586-7614ISSN:1745-170

Schizotypal traits are linked to dopamine-induced striato-cortical decoupling: a randomized double-blind placebo-controlled study

The dopamine hypothesis of schizophrenia implies that alterations in the dopamine system cause functional abnormalities in the brain that may converge to aberrant salience attribution and eventually lead to psychosis. Indeed, widespread brain disconnectivity across the psychotic spectrum has been revealed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic spectrum disorders remains partly unclear-in particular at the low-end of the psychosis continuum. Therefore, we investigated dopamine-induced changes in striatal iFC and their modulation by psychometrically assessed schizotypy. Our randomized, double-blind placebo-controlled study design included 54 healthy, right-handed male participants. Each participant was assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. Participants then received either a placebo or 200 mg of L-DOPA, a dopamine precursor. We analyzed iFC of 6 striatal seeds that are known to evoke modulation of dopamine-related networks. The main effect of L-DOPA was a significant functional decoupling from the right ventral caudate to both occipital fusiform gyri. This dopamine-induced decoupling emerged primarily in participants with low SPQ scores, while participants with high positive SPQ scores showed decoupling indifferently of the L-DOPA challenge. Taken together, these findings demonstrate that schizotypal traits may be the result of dopamine-induced striato-occipital decoupling

The Intricate Relationship between Psychotic-Like Experiences and Associated Subclinical Symptoms in Healthy Individuals

The interplay between subclinical psychotic, negative, and affective symptoms has gained increased attention regarding the etiology of psychosis spectrum and other mental disorders. Importantly, research has tended to not differentiate between different subtypes of psychotic-like experiences (PLE) although they may not have the same significance for mental health. In order to gain information on the subclinical interplay between specific PLE and other symptoms as well as the significance of PLE for mental health, we investigated their specific associations in 206 healthy individuals (20–60 years, 73 females) using correlational and linear regression analyses. PLE were assessed with the Magical Ideation Questionnaire, the revised Exceptional Experiences Questionnaire, and subscales of the Schizotypal Personality Questionnaire (SPQ). The revised Symptom Checklist 90, the SPQ, and the Physical Anhedonia Scale were used to measure subclinical negative symptoms, affective symptoms, and other symptoms such as, emotional instability. As hypothesized, we found that (1) most affective symptoms and all other subclinical symptoms correlated positively with all PLE, whereas we found only partial associations between negative symptoms and PLE. Notably, (2) magical ideation and paranormal beliefs correlated negatively with physical anhedonia. In the regression analyses we found (3) similar patterns of specific positive associations between PLE and other subclinical symptoms: Suspiciousness was a specific predictor of negative-like symptoms, whereas ideas of reference, unusual perceptual experiences, and dissociative anomalous perceptions specifically predicted anxiety symptoms. Interestingly, (4) ideas of reference negatively predicted physical anhedonia. Similarly, paranormal beliefs were negatively associated with constricted affect. Moreover, odd beliefs were a negative predictor of depression, emotional instability, and unspecific symptoms. Our findings indicated that subtypes of PLE are differentially implicated in psychological functioning and should therefore not be categorized homogeneously. Moreover, paranormal beliefs, odd beliefs, and partly ideas of reference might also contribute to subjective well being in healthy individuals. Our results might serve as a starting point for longitudinal studies investigating the interplay of subtypes of subclinical symptoms along a psychopathological trajectory leading to mental disorders. Importantly, this research might help to improve therapeutic strategies for psychosis prevention