The relationship between childhood trauma, psychotic symptoms, and cognitive schemas in patients with schizophrenia, their siblings, and healthy controls: results from the EU-GEI study.

BACKGROUND: The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms. METHODS: Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale. RESULTS: Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ. CONCLUSIONS: Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.

Discriminant analysis using MRI asymmetry indices and cognitive scores of women with temporal lobe epilepsy or schizophrenia.

PURPOSE: This study aims to assess the diagnostic power of brain asymmetry indices and neuropsychological tests for differentiating mesial temporal lobe epilepsy (MTLE) and schizophrenia (SCZ). METHODS: We studied a total of 39 women including 13 MTLE, 13 SCZ, and 13 healthy individuals (HC). A neuropsychological test battery (NPT) was administered and scored by an experienced neuropsychologist, and NeuroQuant (CorTechs Labs Inc., San Diego, California) software was used to calculate brain asymmetry indices (ASI) for 71 different anatomical regions of all participants based on their 3D T1 MR imaging scans. RESULTS: Asymmetry indices measured from 10 regions showed statistically significant differences between the three groups. In this study, a multi-class linear discriminant analysis (LDA) model was built based on a total of fifteen variables composed of the most five significantly informative NPT scores and ten significant asymmetry indices, and the model achieved an accuracy of 87.2%. In pairwise classification, the accuracy for distinguishing MTLE from either SCZ or HC was 94.8%, while the accuracy for distinguishing SCZ from either MTLE or HC was 92.3%. CONCLUSION: The ability to differentiate MTLE from SCZ using neuroradiological and neuropsychological biomarkers, even within a limited patient cohort, could make a substantial contribution to research in larger patient groups using different machine learning techniques.

Menstrual Cycle-Related Changes in Women with Schizophrenia: A Resting-State fMRI Study.

INTRODUCTION: Different influences of ovarian hormones in schizophrenia (SCZ) have been reported, but no study to date has assessed their effects on the brain dynamics at rest. The present study aimed to examine the hormonal and clinical changes related to the menstrual cycle and alterations in the resting-state functional connectivity (RS-FC) depending on cycle phase and/or hormonal fluctuations in SCZ. METHOD: This study was conducted based on both between- and within-subject experimental designs, including 13 clinically stable female patients with SCZ (32 ± 7.7 years) and 13 healthy women (30 ± 7.3 years). RS-functional magnetic resonance imaging (fMRI) scanning, as well as hormonal and clinical assessments, was applied to each participant twice during two cycle phases: early follicular and mid-luteal. RESULTS: A difference in mid-luteal progesterone levels was found between groups, with a large effect size (Cohen's d) of 0.8 (p < 0.05). Also, the estradiol levels negatively correlated with the negative symptom severity of the patients during their mid-luteal phase. In the patients, estrogen positively correlated with the auditory network connectivity in the left amygdala during the early follicular phase. In the controls, progesterone had positive correlations with the connectivity of the posterior default mode and the left frontoparietal networks in the bilateral precuneus during the early follicular phase and had a negative correlation with the executive control network connectivity in the mid-luteal phase. CONCLUSION: The present study showed hormonal differences between groups and suggested that the levels of cycle-dependent hormones might be associated with the changes in clinical symptom severity and the RS-FC in the groups. Our RS-fMRI findings warrant further investigation.

Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1ß levels in patients with schizophrenia spectrum disorder and their siblings.

OBJECTIVE: There is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigate for the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia. METHOD: Sera of 148 patients with schizophrenia spectrum disorders (SCZ), 139 unaffected siblings (SIB) and 210 controls were investigated. Serum interleukin (IL)-1ß levels were measured by ELISA, and TRP, KYN and kynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, we collected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R in SIB and control groups. RESULTS: Compared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significant differences only between SCZ and controls (p < 0.01). KYNA levels of both SCZ (p ≤ 0.001) and SIB (p < 0.05) were higher than controls. No statistical significance was found for KYN levels across groups. SCZ and SIB groups had higher serum IL-1ß levels than controls (p ≤ 0.001). CONCLUSIONS: Patients with SCZ and their siblings exhibited similar clinical features and TRP metabolite levels suggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increased risk to schizophrenia. Elevation of IL-1ß is one of the factors promoting overconsumption of the TRP-KYN pathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.

Relationship of negative symptom severity with cognitive symptoms and functioning in subjects at ultra-high risk for psychosis.

AIM: Negative symptoms and cognition are related with functioning in schizophrenia. However, it is not clear whether they have a similar effect in individuals at ultra-high risk (UHR) for psychosis. In this study, we aimed to explore relationship of negative symptoms with cognition and functioning cross-sectionally in people with UHR for psychosis. METHODS: In total, 107 people participated in this study. We assessed negative symptoms with Scale for Negative Symptoms (SANS). We applied a cognitive battery including seven tests. We evaluated functioning by using Global Assessment of Functioning Scale and work/study status as an indicator of role functioning. RESULTS: SANS scores were correlated to global functioning cross-sectionally. SANS total score was correlated to cognitive test scores related to cognitive flexibility and attention. Only Trail Making Test B (TMT B) was negatively correlated to global functioning. SANS-affective blunting and SANS-avolition scores were independently related to global functioning. There was a significant indirect effect of the TMT B and composite attention scores on global functioning through negative symptoms indicating a complete mediation. CONCLUSION: Our findings suggest that negative symptoms, particularly avolition have an impact on functioning and the association of cognition with functioning was mediated by negative symptoms in UHR.

Lower prepulse inhibition in clinical high-risk groups but not in familial risk groups for psychosis compared with healthy controls.

AIM: Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. METHODS: We studied PPI in individuals within three groups: ultra-high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At-Risk Mental States (CAARMS). We collected clinical data using the BPRS-E, SANS and SAPS when individuals with UHR were antipsychotic-naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. RESULTS: PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. CONCLUSIONS: Our findings suggest that clinical and familial high-risk groups for psychosis have different patterns of PPI.

Neuroimaging Findings in Sepsis-Induced Brain Dysfunction: Association with Clinical and Laboratory Findings.

BACKGROUND: Incidence and patterns of brain lesions of sepsis-induced brain dysfunction (SIBD) have been well defined. Our objective was to investigate the associations between neuroimaging features of SIBD patients and well-known neuroinflammation and neurodegeneration factors. METHODS: In this prospective observational study, 93 SIBD patients (45 men, 48 women; 50.6 ± 12.7 years old) were enrolled. Patients underwent a neurological examination and brain magnetic resonance imaging (MRI). Severity-of-disease scoring systems (APACHE II, SOFA, and SAPS II) and neurological outcome scoring system (GOSE) were used. Also, serum levels of a panel of mediators [IL-1ß, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, TNF-α, complement factor Bb, C4d, C5a, iC3b, amyloid-ß peptides, total tau, phosphorylated tau (p-tau), S100b, neuron-specific enolase] were measured by ELISA. Voxel-based morphometry (VBM) was employed to available patients for assessment of neuronal loss pattern in SIBD. RESULTS: MRI of SIBD patients were normal (n = 27, 29%) or showed brain lesions (n = 51, 54.9%) or brain atrophy (n = 15, 16.1%). VBM analysis showed neuronal loss in the insula, cingulate cortex, frontal lobe, precuneus, and thalamus. Patients with abnormal MRI findings had worse APACHE II, SOFA, GOSE scores, increased prevalence of delirium and mortality. Presence of MRI lesions was associated with reduced C5a and iC3b levels and brain atrophy was associated with increased p-tau levels. Regression analysis identified an association between C5a levels and presence of lesion on MRI and p-tau levels and the presence of atrophy on MRI. CONCLUSIONS: Neuronal loss predominantly occurs in limbic and visceral pain perception regions of SIBD patients. Complement breakdown products and p-tau stand out as adverse neuroimaging outcome markers for SIBD.

Effects of Gender Reassignment on Quality of Life and Mental Health in People with Gender Dysphoria.

OBJECTIVE: Our purpose was to compare the life style, family and social relationships (social adaptation) and the quality of life in people with gender dysphoria with and without history of sex reassignment surgery. METHOD: Twenty  individuals (SR group) who were earlier followed   in Istanbul University Psychiatry Department Psychoneurosis and Psychotherapy Unit with gender dysphoria diagnosis in  order  to  have confirmative reports for the sex reassignment (SR) surgery were interviewed at least one year after the surgery. For comparison, 50 individuals with gender dysphoria (NSR group) who had recently applied to the same unit were interviewed. Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I), Family Assessment Device (FAD), Multidimensional Scale for Perceived Social Support (MSPSS), World Health Organization Quality of Life Scale (WHOQOL-BREF) were administered. RESULTS: In the SR group, concerns about gender related discrimination and victimization were lower, but concerns related to the disclosure of transgender identity were higher compared to the NSR group. The SR group scored lower on FAD Affective Involvement, Problem Solving, Affective Responsiveness subscales, but scored higher on MSPSS family subscale and psychological domain of WHOQOL-BREF. CONCLUSION: The sex reassignment surgeries (SRS) required for legal change in gender status of individuals with gender dysphoria are helpful in relieving the conflicts. SRS causes improvements in the quality of life, family support, interpersonal relationships and reduces the concerns about the gender related discrimination and victimization.

Relationship of obsessive-compulsive symptoms to clinical variables and cognitive functions in individuals at ultra high risk for psychosis.

Few studies have investigated the relationship between obsessive-compulsive symptoms (OCS) and clinical variables, and cognition in individuals at ultra high-risk (UHR) for psychosis. The aim of this study was to evaluate the frequency of OCS and their relationship with clinical variables and cognitive functions in individuals at UHR. Eighty-four individuals at UHR for psychosis were administered the Brief Psychiatric Rating Scale, the Yale-Brown Obsession Compulsion Symptom Check List and, the Calgary Depression Scale for Schizophrenia. A cognitive test battery was also applied. We compared the clinical, functional, and cognitive parameters of individuals at UHR with and without OCS and healthy controls. Thirty-five percent of the UHR sample had at least two obsessions/compulsions. The duration of subthreshold psychotic symptoms was longer in individuals with OCS. Those who can work/study before first presentation were more frequent in OCS-positive group. CDSS scores were higher in those with OCS. Compared to controls, OCS-negative group's performance was worse in 8 cognitive test items, while OCS-positive group performed worse in only one cognitive test item. Our findings suggest that OCS are common in the UHR group. OCS might be related to higher level of depression, but better work/study performance, and less cognitive deficits in UHR group.

Volumetric differences suggest involvement of cerebellum and brainstem in chronic migraine.

BACKGROUND: Chronic migraine (CM) is a disabling neurologic condition that often evolves from episodic migraine. There has been mounting evidence on the volumetric changes detected by magnetic resonance imaging (MRI) technique in migraineurs. These studies mainly focused on episodic migraine patients and less is known about the differences in CM patients. METHOD: A total of 24 CM patients and 24 healthy control individuals (all females) were included in this study. All participants underwent neurological examination and MRI. High-resolution anatomical MRI images were processed with an automated segmentation method (FreeSurfer). White-matter abnormalities of the brain were also evaluated with the Age-Related White-Matter-Changes Scale. RESULTS: The volumes of the cerebellum and brainstem were found to be smaller in CM patients compared to healthy controls. White-matter abnormalities were also found in CM patients, specifically in the bilateral parieto-occipital areas. There was no correlation between the clinical variables and volume decrease in these regions. CONCLUSION: CM patients showed significant volume differences in infratentorial areas and white-matter abnormalities in the posterior part of the brain. It is currently unclear whether the structural brain changes seen in migraine patients are the cause or the result of headaches. Longitudinal volumetric neuroimaging studies with larger groups, especially on the chronification of migraine, are needed to shed light on this topic.

Clinical variables associated with suicide attempts in schizophrenia before and after the first episode.

The aim of this study was to investigate variables associated with suicide attempts in schizophrenia before and after the first episode. We evaluated history of past sucide attempts, clinical symptoms, level of functioning and cognitive performances of 172 patients with first-episode schizophrenia at first admission. Information was collected regarding clinical symptom severity, treatment compliance, and suicide attempts during the follow-up. We found that 16.5% of the patients attempted suicide before admission, and 6.2% of them attempted suicide during the follow-up. The patients who had attempted suicide before admission were mostly women, and more likely to be hospitalized in first year of follow up. BPRS-depression subscale score at admission and alcohol/substance use appeared as independent variables that found associated with suicide attempts prior to admission in logistic regression analysis. The patients who attempted suicide during the follow-up had significantly higher BPRS-depression subcale scores at sixth months of follow-up. Treatment compliance during the first 6 months and duration of remission was lower in this group. Our findings suggest that longer duration of first hospital treatment, the presence of depressive symptoms, and nonadherence to treatment in early phases of follow up after FES are predictors of suicide attempts. On the other hand, keeping remission during the follow-up protects against suicide attempts.