Non-psychotic Individuals Research Articles

Comparative Analysis of Fecal Microbiota Between Adolescents with Early-Onset Psychosis and Adults with Schizophrenia.

Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut-brain axis in psychiatric disorders.

White matter abnormalities in the amputation variant of body integrity dysphoria

“Body integrity dysphoria” (BID) is a severe condition affecting nonpsychotic individuals. In the amputation variant of BID, a limb may be experienced as not being part of the body, despite normal anatomical development and intact sensorimotor functions. We previously demonstrated altered brain structural (gray matter) and functional connectivity in 16 men with BID with a long-lasting and exclusive desire for left leg amputation. Here, we aimed to identify, in the same sample, altered patterns of white matter structural connectivity. Fractional anisotropy (FA), derived from diffusion tensor imaging data, was considered as a measure of structural connectivity. Results showed reduced structural connectivity of: (i) the right superior parietal lobule (rSPL) with the right cuneus, with the superior occipital and with the posterior cingulate gyri, (ii) the pars orbitalis of the right middle frontal gyrus (rMFGOrb) with the putamen, and (iii) the left middle temporal gyrus (lMTG) with the pars triangularis of the left inferior frontal gyrus. Increased connectivity was found between the right paracentral lobule (rPLC) and the right caudate nucleus. By using a complementary method of investigation, we confirmed and extended previous results from the same sample of individuals with BID, showing structural alterations between areas tuned to the processing of the sensorimotor representations of the affected leg (rPCL), and to higher-order components of bodily representation such as the body image (rSPL) and visual processing. Alongside this network for bodily awareness, other networks such as the limbic (rMFGOrb) and the mirror (lMTG) systems showed alterations in structural connectivity. These findings consolidate current understanding of the neural correlates of the amputation variant of BID, which might in turn guide diagnostics and rehabilitative treatments.

Salient Properties in Bimanual Haptic Volume Perception: Influence of Object Shape, Finger Pair, and Schizotypal Personality Traits.

Bimanual haptic volume perception refers to somatosensory access to volume information through both hands, and the characteristics that influence this perception remain unclear. This article investigated the influence of target object shapes and finger pairs on bimanual haptic perception; in addition, associations of bimanual haptic impairment and schizotypal features in nonpsychotic individuals were investigated. Twenty blindfolded participants bimanually discriminated volume variations in regular solid objects under different shape (tetrahedron, cube, or sphere) and finger pair (high- or low-sensitivity pairs) conditions using a newly developed bimanual haptic volume presentation device. Discrimination thresholds were then associated with schizotypal traits using the Chinese version of the Schizotypal Personality Questionnaire. Target object shape and finger pairs significantly influenced bimanual haptic volume perception. Volume discrimination thresholds were significantly higher with the tetrahedron stimuli than the cubic or spherical stimuli in high-sensitivity pair conditions, but no significant differences among shapes were found in low-sensitivity pair conditions. Moreover, volume discrimination thresholds with high-sensitivity pairs were correlated with the paranoid score of the schizotypal personality questionnaire. The findings provide initial evidence toward understanding the nature of bimanual haptic volume perception, including the properties of objects, individuals, and object-individual interfaces.

White Matter Matters: Unraveling Violence in Psychosis and Psychopathy

Individuals with psychosis have an increased risk of committing acts of violence. Providing neurobiological evidence for the extent to which violence in psychosis is driven by psychotic symptoms and/or antisocial traits could have important clinical and legal implications. White matter (WM) abnormalities have been reported in individuals with psychosis and those with antisocial traits. However, it is not clear if WM abnormalities in violent psychosis (violent PSY) resemble those previously found in non-violent psychosis (non-violent PSY), non-psychotic individuals with antisocial traits (violent non-PSY), or both.

Thirteen year follow up of long term treated psychotic disorder: Personality aspects

IntroductionPsychotic disorders often cause a drastic change in the life situation of the affected individual. Personality is an aspect that can affect the symptoms and social function in psychotic disorders.ObjectivesNo study has examined stability of personality traits exceeding five years in patients with schizophrenia. The aim of this study was to investigate the stability of personality traits over a 13-year period among patients with psychotic disorder and healthy individuals and to evaluate case-control differences.MethodsAt three occasions during a 13-year period patients with psychotic disorders (n=28) and non-psychotic individuals (n=57) completed Swedish universities Scales of Personality (SSP). For all the individuals within- and between-subject analyses were performed at three occasions for all 13 subscales and the three overall factors of SSP. Correlations, means and SDs were calculated.ResultsTests of within-subject correlations showed differences in two subscales: Lack of Assertiveness, which were influenced by age and Physical Trait Aggression, where patients ratings were stable, whereas controls rated themselves less aggressive at higher age. Between-subjects correlations showed differences regarding any of the parameters diagnosis, time, age, gender or age x gender in nine of the 13 subscales as well as in factor Neuroticism.ConclusionsLong term follow-up showed a generally high stability of personality traits measured with SSP, especially among patients. Between-subject analyses over the 13 years showed that patients differed compared to controls for the SSP factor Neuroticism as well as the subscale Detachment, which is in accordance with previous studies.

White Matter Matters: Unraveling Violence in Psychosis and Psychopathy

Abstract Individuals with psychotic disorders have an increased risk of committing acts of violence. Neurobiological support for the extent to which violence in psychosis is driven by psychotic symptoms and/or antisocial traits could have clinical and legal implications. Neuroimaging studies have reported white matter (WM) abnormalities in individuals with psychosis and in those with antisocial traits. However, it is unknown whether WM abnormalities in psychosis patients with a history of violence (violent-PSY) resemble those found in nonviolent psychosis patients (nonviolent PSY), violent nonpsychotic individuals (violent non-PSY), or both. Diffusion tensor imaging scans from 301 males including violent-PSY (n = 28), violent non-PSY (n = 20), nonviolent PSY (n = 58), and healthy controls (HC, n = 195) were analyzed with tract-based spatial statistics. Fractional anisotropy (FA), mean, axial and radial (RD) diffusivity were compared between groups. Psychopathic traits in the violent groups were measured with Psychopathy Checklist-revisited (PCL-R). Violent-PSY had globally lower FA and higher RD, compared with nonviolent PSY. Both psychosis groups and violent non-PSY group had widespread disruptions in WM compared with HC. There were no significant WM differences between violent-PSY and violent non-PSY. PCL-R scores did not differ between the violence groups and were associated with higher RD in corpus callosum. Here we demonstrate a widespread pattern of reduced WM integrity in violent-PSY compared with nonviolent PSY. The lack of significant WM and PCL-R differences between the violence groups, together with the positive association between PCL-R and WM deficits in violent-PSY and violent non-PSY may indicate shared neurobiological underpinnings of trait violence.

S161. DYNAMIC FUNCTIONAL NETWORK CONNECTIVITY COMPARING AUDITORY VERBAL HALLUCINATIONS IN PSYCHOTIC AND NON-PSYCHOTIC SUBJECTS

BackgroundAuditory verbal hallucinations (AVH) are often seen as a hallmark of schizophrenia, but can also occur in the general healthy population. While AVH in non-clinical populations might offer an opportunity to study them in isolation, it remains debatable whether the mechanisms underlying AVH are the same in clinical and non-clinical populations. For example, non-clinical populations are reported to attribute lower emotional valence to their AVH. Such differences in phenomenology are hypothesized to arise from differences on the neurobiological level. With the current study, we employ a data-driven approach to define brain networks involved in AVH in clinical and non-clinical subjects, and test whether dynamic differences in network connectivity exist between these groups.MethodsFunctional magnetic resonance imaging data of 21 non-psychotic individuals and 21 matched psychotic patients with frequent AVH were obtained. During scanning, subjects manually indicated the on- and offset of their AVH. Using independent component (IC) analysis, the data were split into 72 statistically independent spatial maps and their time courses. These time courses were regressed with the AVH time courses. With a one sample t-test on the beta weights, we selected those ICs that related to AVH in both groups for further dynamic functional network connectivity analysis. To identify functional connectivity states, k-means clustering was implemented on correlation matrices acquired using sliding windows. Group differences between these states were determined with two-sample t-tests.ResultsBoth groups experienced AVH during scanning, with a mean number of 24.71 AVH episodes in the clinical and 17.14 episodes in the non-clinical group. We identified seven ICs with time courses significantly related to the occurrence of AVH in both groups. The auditory, sensorimotor, and posterior salience network were positively related to AVH occurrence. The ventral default mode network (DMN), anterior salience network and a network consisting of (para-)hippocampal areas were negatively related to AVH.While in general, networks related to AVH were similar in both groups, a significant difference between the two groups was found in the mean dwell time in states characterized by varying connectivity between these networks. Psychotic patients spent more time in a state of low connectivity (r < 0.055) between all AVH-related networks. Non-psychotic patients dwelled longer in a different state, where some weak correlations between networks were present (.15 > r ≥ .10). Specifically, networks positively related to AVH showed small negative correlations with each other, and a small negative relationship with the DMN. At the same time, the anterior salience network displayed a small positive relationship with the sensorimotor, auditory and posterior salience networks.DiscussionOur findings suggest that similar brain networks underlie AVH in non-psychotic and psychotic individuals, but that the groups differ in terms of connectivity between those networks. Among the involved networks are those typically associated with AVH in psychotic patients, such as the DMN and auditory network. During the experience of AVH, psychotic individuals are more likely to show a state defined by segregation of the AVH-related networks. On the contrary, during AVH non-psychotic individuals are in a state defined by more connectivity between the networks. This suggests that a distinction between clinical and non-clinical AVH may have its neurobiological basis in the extend of disruption of involved network connectivity.

M20. CYTOKINE LEVELS THROUGHOUT PREGNANCY AND RISK FOR PSYCHOSIS IN ADULT OFFSPRING: EARLY PREGNANCY MATTERS

BackgroundSchizophrenia has been associated with pregnancy and birth complications, and fetal exposure to inflammation is thought to be a common underlying mechanism. However, it is unclear whether the risk associated with inflammation is specific to particular phases of pregnancy, as no prior studies have examined maternal serum samples across multiple assessments from the first trimester onward. This study examined differences in longitudinal patterns of maternal serum levels of TNFa, IL-1b, IL-5, IL-6, IL-8, IL-10, and IL-17a across pregnancy for offspring who were later ascertained as having a psychotic disorder diagnosis, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls.MethodsParticipants included 90 offspring, 79 siblings, and 273 matched controls from the Philadelphia cohort of the National Collaborative Perinatal Project. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Cytokine levels were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth.ResultsLevels of pro-inflammatory TNFa, IL-1b, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis relative to maternal serum of non-psychotic siblings and matched controls. These differences were maximal in first half of pregnancy (7–20 weeks), tapering to non-significant during the second half of pregnancy.DiscussionThese findings elucidate the importance of exposure to elevated maternal pro-inflammatory cytokine levels in early pregnancy to the etiology of psychosis.

Cytokine concentrations throughout pregnancy and risk for psychosis in adult offspring: a longitudinal case-control study

Schizophrenia has been associated with pregnancy and birth complications and fetal exposure to inflammation is thought to be a common underlying mechanism. However, whether the risk is specific to particular phases of pregnancy is unclear. The aim of this study was to characterise and compare longitudinal patterns of maternal serum concentrations of cytokines across pregnancy between offspring who were later ascertained to have a psychotic disorder, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. The National Collaborative Perinatal Project was a large-scale prospective longitudinal study that assessed the effects of perinatal factors on infant and child development. At sites across the USA, over 50 000 pregnant women were enrolled during prenatal clinical visits between 1959 and 1965. The present study draws from the Philadelphia cohort, which includes 9236 surviving offspring of 6753 pregnant women. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Concentrations of TNFα, IL-1β, IL-5, IL-6, IL-8, IL-10, and IL-17a were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. We characterized cytokine patterns with linear mixed models. Our final sample comprised 90 cases, 79 siblings (of 40 cases), and 273 matched controls. Concentrations of proinflammatory cytokines TNFα, IL-1β, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis compared with maternal serum of matched controls. These differences were greatest in the first half of pregnancy (7-20 weeks), with no difference observed during the second half of pregnancy. Our results suggest that exposure to high maternal proinflammatory cytokine concentrations in early pregnancy might play a part in psychosis. These findings place the timing of risk associated with maternal inflammation much earlier in prenatal development than previously documented in humans and provide insight into a potential developmental pathway to the disorder. National Institute of Mental Health (P50) Silvio O Conte Center at Johns Hopkins, Stanley Foundation, March of Dimes, Yale University, National Science Foundation, and National Institute of Child Health and Human Development/Division of Intramural Population Health Research.

Psychotic versus non-psychotic bipolar disorder: Socio-demographic and clinical profiles in an Italian nationwide study

Psychotic versus non-psychotic patients with bipolar disorder have been traditionally associated with different unfavorable clinical features. In this study on bipolar Italian patients, we aimed to compare clinical and demographic differences between psychotic and non-psychotic individuals, exploring clinical factors that may favor early diagnosis and personalized treatment. A total of 1671 patients (males: n = 712 and females: n = 959; bipolar type 1: n = 1038 and bipolar type 2: n = 633) from different psychiatric departments were compared according to the lifetime presence of psychotic symptoms in terms of socio-demographic and clinical variables. Chi-square tests for qualitative variables and Student's t-tests for quantitative variables were performed for group comparison, and a multivariable logistic regression was performed, considering the lifetime psychotic symptoms as dependent variables and socio-demographic/clinical characteristics as independent variables. Psychotic versus non-psychotic bipolar subjects resulted to: be more frequently unemployed (p < 0.01) and never married/partnered (p < 0.01); have an earlier age at onset (p < 0.01); more frequently receive a first diagnosis different from a mood disorder (p < 0.01); have a shorter duration of untreated illness (p < 0.01); have a more frequently hypomanic/manic prevalent polarity (p < 0.01) and a prevalent manic-depressive type of cycling (p < 0.01); present a lower lifetime number of depressive episodes (p < 0.01), but have more manic episodes (p < 0.01); and less insight (p < 0.01) and more hospitalizations in the last year (p < 0.01). Multivariable regression analysis showed that psychotic versus non-psychotic bipolar patients received more frequently a first diagnosis different from bipolar disorder (odds ratio = 0.64, 95% confidence interval = [0.46, 0.90], p = 0.02) or major depressive disorder (odds ratio = 0.66, 95% confidence interval = [0.48, 0.91], p = 0.02), had more frequently a prevalent manic polarity (odds ratio = 1.84, 95% confidence interval = [1.14, 2.98], p < 0.01) and had a higher number of lifetime manic episodes (more than six) (odds ratio = 8.79, 95% confidence interval = [5.93, 13.05], p < 0.01). Lifetime psychotic symptoms in bipolar disorder are associated with unfavorable socio-demographic and clinical features as well as with a more frequent initial misdiagnosis.

Individuals with 22q11.2 deletion syndrome show intact prediction but reduced adaptation in responses to repeated sounds: Evidence from Bayesian mapping.

One of the most common copy number variants, the 22q11.2 microdeletion, confers an increased risk for schizophrenia. Since schizophrenia has been associated with an aberrant neural response to repeated stimuli through both reduced adaptation and prediction, we here hypothesized that this may also be the case in nonpsychotic individuals with a 22q11.2 deletion.We recorded high-density EEG from 19 individuals with 22q11.2 deletion syndrome (12–25 years), as well as 27 healthy volunteers with comparable age and sex distribution, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Using posterior probability maps and dynamic causal modelling we tested three different models accounting for repetition dependent changes in cortical responses as well as in effective connectivity; namely an adaptation model, a prediction model, and a model including both adaptation and prediction.Repetition-dependent changes were parametrically modulated by a combination of adaptation and prediction and were apparent in both cortical responses and in the underlying effective connectivity. This effect was reduced in individuals with a 22q11.2 deletion and was negatively correlated with negative symptom severity. Follow-up analysis showed that the reduced effect of the combined adaptation and prediction model seen in individuals with 22q11.2 deletion was driven by reduced adaptation rather than prediction failure. Our findings suggest that adaptation is reduced in individuals with a 22q11.2 deletion, which can be interpreted in light of the framework of predictive coding as a failure to suppress prediction errors.

Clinical correlates of subsyndromal depression in African American individuals with psychosis: The relationship with positive symptoms and comorbid substance dependence

Patients with psychosis exhibit subsyndromal depressive symptoms during the course of illness and yet the clinical correlates of these symptoms remain under-investigated. We aimed to investigate the clinical correlates of subsyndromal depression in psychosis including the extent to which they mediate commonly observed comorbid substance dependence. We developed a model of depression in a non-clinical sample recruited via Amazon's Mechanical Turk (N = 266), and confirmed that model in a locally recruited African-American clinical sample comprising psychotic and non-psychotic individuals (N = 256). Using scores from this model we tested: the strength of relationships between depressive symptomatology and positive, negative and disorganized symptoms in a range of psychotic disorders; whether depressive symptoms were higher in individuals with affective psychoses versus schizophrenia; and if depressive symptomatology mediated the relationship between psychosis and substance dependence. Subsyndromal depressive symptomatology was significantly higher in individuals with psychosis than without psychosis, but did not significantly differ between affective and non-affective psychotic groups. Depressive symptomatology was significantly related to positive (but not negative or disorganized) psychotic symptoms, and mediated the relationship between psychosis and substance dependence. The present study underlines the importance of assessing subsyndromal depression in patients with psychosis, and generates a number of testable predictions for future work. In particular, the examination of the relationships between comorbid psychopathology, namely depression and substance abuse, may improve insight into the neurobiology of psychosis.

Stability of personality traits over a five-year period in Swedish patients with schizophrenia spectrum disorder and non-psychotic individuals: a study using the Swedish universities scales of personality

BackgroundPersonality is considered as an important aspect in persons with psychotic disorders. Several studies have investigated personality in schizophrenia. However, no study has investigated stability of personality traits exceeding three years in patients with schizophrenia. This study aims to investigate the stability of personality traits over a five-year period among patients with schizophrenia and non-psychotic individuals and to evaluate case-control differences.MethodsPatients with psychotic disorders (n = 36) and non-psychotic individuals (n = 76) completed Swedish universities Scales of Personality (SSP) at two occasions five years apart. SSP scores were analysed for effect of time and case-control differences by multiple analysis of covariance (MANCOVA) and within-subjects correlation.ResultsMANCOVA within-subjects analysis did not show any effect of time. Thus, SSP mean scale scores did not significantly vary during the five-year interval. Within subject correlations (Spearman) ranged 0.30–0.68 and 0.54–0.75 for the different SSP scales in patients and controls, respectively. Patients scored higher than controls in SSP scales Somatic Trait Anxiety, Psychic Trait Anxiety, Stress Susceptibility, Lack of Assertiveness, Detachment, Embitterment, and Mistrust.ConclusionThe stability of the SSP personality trait was reasonably high among patients with psychotic disorder, although lower than among non-psychotic individuals, which is in accordance with previous research.

22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response.

BackgroundThe 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion.MethodsEighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12–25 years) and sex ratio underwent 128-channel EEG. We recorded the cortical ASSR to a 40 Hz train of clicks, given either at a regular inter-stimulus interval of 25 ms or at irregular intervals jittered between 11 and 37 ms.ResultsHealthy noncarriers expressed a stable ASSR to regular but not in the irregular 40 Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion carriers (ρ = −0.487, P = .041).ConclusionsNonpsychotic 22q11.2 deletion carriers lack efficient phase locking of evoked gamma activity to regular 40 Hz auditory stimulation. This abnormality indicates a dysfunction of fast intracortical oscillatory processing in the gamma-band. Since ASSR was attenuated in nonpsychotic deletion carriers, ASSR deficiency may constitute a premorbid risk marker of schizophrenia.

White Matter Integrity in Genetic High-Risk Individuals and First-Episode Schizophrenia Patients: Similarities and Disassociations.

White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes.

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia.

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders

BackgroundThe long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown. MethodsClinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics. ResultsA total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR=4.825) of developing psychotic disorders, and a reduced risk (HR=0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P<0.001). ConclusionsIn the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes. Significant outcomesIn the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup. LimitationsWhile incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.

Deconstructing Pretest Risk Enrichment to Optimize Prediction of Psychosis in Individuals at Clinical High Risk

Pretest risk estimation is routinely used in clinical medicine to inform further diagnostic testing in individuals with suspected diseases. To our knowledge, the overall characteristics and specific determinants of pretest risk of psychosis onset in individuals undergoing clinical high risk (CHR) assessment are unknown. To investigate the characteristics and determinants of pretest risk of psychosis onset in individuals undergoing CHR assessment and to develop and externally validate a pretest risk stratification model. Clinical register-based cohort study. Individuals were drawn from electronic, real-world, real-time clinical records relating to routine mental health care of CHR services in South London and the Maudsley National Health Service Trust in London, United Kingdom. The study included nonpsychotic individuals referred on suspicion of psychosis risk and assessed by the Outreach and Support in South London CHR service from 2002 to 2015. Model development and validation was performed with machine-learning methods based on Least Absolute Shrinkage and Selection Operator for Cox proportional hazards model. Pretest risk of psychosis onset in individuals undergoing CHR assessment. Predictors included age, sex, age × sex interaction, race/ethnicity, socioeconomic status, marital status, referral source, and referral year. A total of 710 nonpsychotic individuals undergoing CHR assessment were included. The mean age was 23 years. Three hundred ninety-nine individuals were men (56%), their race/ethnicity was heterogenous, and they were referred from a variety of sources. The cumulative 6-year pretest risk of psychosis was 14.55% (95% CI, 11.71% to 17.99%), confirming substantial pretest risk enrichment during the recruitment of individuals undergoing CHR assessment. Race/ethnicity and source of referral were associated with pretest risk enrichment. The predictive model based on these factors was externally validated, showing moderately good discrimination and sufficient calibration. It was used to stratify individuals undergoing CHR assessment into 4 classes of pretest risk (6-year): low, 3.39% (95% CI, 0.96% to 11.56%); moderately low, 11.58% (95% CI, 8.10% to 16.40%); moderately high, 23.69% (95% CI, 16.58% to 33.20%); and high, 53.65% (95% CI, 36.78% to 72.46%). Significant risk enrichment occurs before individuals are assessed for a suspected CHR state. Race/ethnicity and source of referral are associated with pretest risk enrichment in individuals undergoing CHR assessment. A stratification model can identify individuals at differential pretest risk of psychosis. Identification of these subgroups may inform outreach campaigns and subsequent testing and eventually optimize psychosis prediction.

Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is associated with increased rates of psychotic disorders and cognitive deficits, but large scale studies are needed to elucidate their interaction. The objective of this two-center study was to identify the neurocognitive phenotype of individuals with 22q11DS and psychotic disorders. We hypothesized that psychotic 22q11DS individuals compared to nonpsychotic deleted individuals would have more severe neurocognitive deficits, especially in executive function and social cognition. These deficits would be present when compared to IQ- matched individuals with Williams Syndrome (WS).Three groups were ascertained from the Tel Aviv and Philadelphia centers: 22q11DS individuals with a psychotic disorder (n=31), nonpsychotic 22q11DS (n=86) and typically-developing controls (TD, n=828). In Tel Aviv a group of individuals with WS (n=18) matched in IQ to the 22q11DS psychotic group was also included. The Penn Computerized Neurocognitive Battery (CNB) was used to assess a wide-range of cognitive functions and all patients underwent structured psychiatric evaluations. 22q11DS individuals performed poorly on all CNB domains compared to TD. Participants with 22q11DS and psychosis, compared to nonpsychotic 22q11DS, had more severe deficits in global neurocognitive performance (GNP), executive function, social cognition and episodic memory domains. The primary deficits were also significant when comparing the Tel Aviv 22q11DS psychotic group to IQ-matched individuals with WS. In conclusion, 22q11DS individuals with a psychotic disorder have specific neurocognitive deficits that are reliably identified cross nationality using the CNB. These cognitive dysfunctions should be further studied as potential endophenotypes of psychosis in 22q11DS and as targets for intervention.

A linguistic comparison between auditory verbal hallucinations in patients with a psychotic disorder and in nonpsychotic individuals: Not just what the voices say, but how they say it

BackgroundAuditory verbal hallucinations (AVH) in psychotic patients are associated with activation of right hemisphere language areas, although this hemisphere is non-dominant in most people. Language generated in the right hemisphere can be observed in aphasia patients with left hemisphere damage. It is called “automatic speech”, characterized by low syntactic complexity and negative emotional valence. AVH in nonpsychotic individuals, by contrast, predominantly have a neutral or positive emotional content and may be less dependent on right hemisphere activity. We hypothesize that right hemisphere language characteristics can be observed in the language of AVH, differentiating psychotic from nonpsychotic individuals. Method17 patients with a psychotic disorder and 19 nonpsychotic individuals were instructed to repeat their AVH verbatim directly upon hearing them. Responses were recorded, transcribed and analyzed for total words, mean length of utterance, proportion of grammatical utterances, proportion of negations, literal and thematic perseverations, abuses, type-token ratio, embeddings, verb complexity, noun-verb ratio, and open-closed class ratio. ResultsLinguistic features of AVH overall differed between groups F(13,24)=3.920, p=0.002; Pillai’s Trace 0.680. AVH of psychotic patients compared with AVH of nonpsychotic individuals had a shorter mean length of utterance, lower verb complexity, and more verbal abuses and perseverations (all p<0.05). Other features were similar between groups. ConclusionAVH of psychotic patients showed lower syntactic complexity and higher levels of repetition and abuses than AVH of nonpsychotic individuals. These differences are in line with a stronger involvement of the right hemisphere in the origination of AVH in patients than in nonpsychotic voice hearers.