Molecular and micro-architectural mapping of gray matter alterations in psychosis.

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n = 160), individuals who had psychotic experiences (n = 157), patients who experienced a first episode of psychosis (FEP, n = 352), and individuals with chronic SCZ or SAD (n = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α4ß2) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.

Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

Spanish experts consensus on emergency psychiatric care in hospital emergency departments.

BACKGROUND: The demand for urgent psychiatric care is increasing, but in Spain there are no clear recommendations for emergency departments (ED) on how to optimize care for patients with psychiatric emergencies. We aimed to provide expert consensus recommendations on the requirements for general hospitals´ emergency departments to treat patients with urgent psychiatric symptoms. METHODS: We used a modified Delphi technique. A scientific committee compiled 36 statements based on literature search and clinical experience. The statements covered the organizational model, facilities, staffing, safety, patient interventions, and staff training. A panel of 38 psychiatry specialists with expertise in psychiatric emergencies evaluated the questionnaire in two rounds. RESULTS: After two rounds of voting, 30 out of 36 proposed items (83%) were agreed upon. The panel agreed that psychiatric emergencies should be managed in a general hospital, with dedicated facilities for patient assessment, direct supervision of patients at risk, and an observation unit run by the psychiatric service. In addition to the psychiatrist, the ED should have specialist nurses and security staff available 24/7. Social workers should also be readily available. ED and consulting rooms should be designed to ensure patient and staff safety. A triage system should be established for patients with psychiatric symptoms, with medical evaluation preceding psychiatric evaluation. Guidance on supplies, equipment, and staff training is also provided. CONCLUSION: All ED in general hospitals should have adequate resources to handle any psychiatric emergency. This paper provides recommendations on the minimum requirements to achieve this goal.

Exploring genetic testing requests, genetic alterations and clinical associations in a cohort of children with autism spectrum disorder.

Several studies show great heterogeneity in the type of genetic test requested and in the clinicopathological characteristics of patients with ASD. The following study aims, firstly, to explore the factors that might influence professionals' decisions about the appropriateness of requesting genetic testing for their patients with ASD and, secondly, to determine the prevalence of genetic alterations in a representative sample of children with a diagnosis of ASD. Methods: We studied the clinical factors associated with the request for genetic testing in a sample of 440 children with ASD and the clinical factors of present genetic alterations. Even though the main guidelines recommend genetic testing all children with an ASD diagnosis, only 56% of children with an ASD diagnosis were genetically tested. The prevalence of genetic alterations was 17.5%. These alterations were more often associated with intellectual disability and dysmorphic features. There are no objective data to explicitly justify the request for genetic testing, nor are there objective data to justify requesting one genetic study versus multiple studies. Remarkably, only 28% of males were genetically tested with the recommended tests (fragile X and CMA). Children with dysmorphic features and organic comorbidities were more likely to be genetic tested than those without. Previous diagnosis of ASD (family history of ASD) and attendance at specialist services were also associated with Genetically tested Autism Spectrum Disorder GTASD. Our findings emphasize the importance of establishing algorithms to facilitate targeted genetic consultation for individuals with ASD who are likely to benefit, considering clinical phenotypes, efficiency, ethics, and benefits.

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study.

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

miRNAs as biomarkers of autism spectrum disorder: a systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36 months of age. Social interaction deficiencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difficult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and affect the expression of genes related to different neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in different body fluids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in different studies using the mean values. In addition, we summarized p values for differential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the meta-analysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are differentially expressed in various tissues and body fluids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fluid for miRNA measurements, because it is easy to collect from children compared to other biological fluids.

Childhood and adolescent trauma and dissociation: The mediating role of rumination, intrusive thoughts and negative affect.

Dissociation is a complex phenomenon which is present in a wide variety of psychiatric disorders and also in the general population. The objective of this study was to examine the relationship between childhood and adolescent traumas and development of dissociative phenomena in a nonclinical population, emphasizing the potentially mediating role of rumination, intrusive thoughts and negative affect in a population with no psychiatric pathology in adulthood. The sample was comprised of 337 participants from the general population (58.8% women) with a mean age of 33.10 years (SD: 14.08). They completed the Juvenile Victimization Questionnaire (JVQ), the Ruminative Response Scale (RRS), the White Bear Suppression Scale (WBSI), the Dissociative Experience Scale, 2d ver. Rev. (DES-II) and the Depression, Anxiety and Stress Scale (DASS-21). The results supported the starting hypotheses showing a positive correlation between childhood and adolescent trauma and dissociation, and between childhood and adolescent trauma and rumination, intrusive thoughts and negative affect, and mediation of these variables between childhood and adolescent trauma and dissociative states. The relationship between trauma in early ages and dissociation in adulthood is complex. Although the design used in this study was cross-sectional, the results are compatible with the starting hypothesis that rumination, intrusive thoughts and negative affect mediate this relationship.

Dissociation as a Mediator of Traumatic Childhood Experiences and Ideas of Reference.

Ideas of reference (IR) - self-attributions about what happens in the social environment are a frequent phenomenon present in a wide variety of people with mental health disorders as well as in the nonclinical population. The purpose of this study was to find out the relationship between traumatic childhood experiences, IR and dissociative states in the nonclinical population, emphasizing the potential mediating role of dissociation between traumatic experiences and IR. The sample was comprised of 337 participants from the general population (58.8% women) with a mean age of 33.20 years (SD = 14.08). They filled in the Juvenile Victimization Questionnaire (JVQ), the Dissociative Experiences Scale-II (DES-II) and the Referential thinking Scale (REF). The results supported the original hypotheses and showed that the participants with higher frequency of IR reported more childhood traumatic (χ2 (2) = 64.33, p < .001, f = .39, 1- ß = .99) and dissociative experiences (χ2 (2) = 50,414, p < .001, f = .38, 1- ß = .99), and that dissociative states (ß = .12, p < .05; 95%CI [.07, .19]; c´ = .26, p < .001), specifically absorption (ß = .09, p < .05; 95% CI [.03, .15]; c´ = .26, p < .001), mediated between traumatic childhood experiences and referential thinking. It was concluded that the relationship between traumatic experiences and IR is complex and may be mediated by variables such as dissociation.

Aripiprazole vs Risperidone Head-to-Head Effectiveness in First-Episode Non-Affective-Psychosis: A 3-Month Randomized, Flexible-Dose, Open-Label Clinical Trial.

BACKGROUND: Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second-generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short term of aripiprazole and risperidone after FEP outbreak. METHODS: From February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode drug-naïve patients were randomly assigned to aripiprazole (n = 136) or risperidone (n = 130) and followed-up for 12 weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. RESULTS: The overall dropout rate at 12 weeks was small (6.39%). Effectiveness measures were similar between treatment arms as treatment discontinuation rates (χ 2 = 0,409; P = .522), and mean time to all-cause discontinuation (log rank χ 2 = -1.009; P = .316) showed no statistically significant differences. Despite no statistically significant differences between groups regarding clinical efficacy, aripiprazole required higher chlorpromazine equivalent dosage (χ 2 = 2.160; P = .032) and extended mean time (W = 8183.5; P = .008) to reach clinical response. Sex-related adverse events and rigidity were more frequent in the risperidone group, whereas sialorrhea was on the aripiprazole group. CONCLUSIONS: No differences regarding effectiveness were found between aripiprazole and risperidone for the short-phase treatment of FEP. Despite the importance of efficacy during this phase, differences in side effect profiles and patient's preferences are essential factors that may lead clinical decisions for these patients. CLINICALTRIALS.GOV: NCT02532491. Effectiveness of Second-Generation Antipsychotics in First Episode Psychosis Patients: 1-year Follow-up (PAFIP3_1Y).

Clinical characterization of brief psychotic disorders triggered by the COVID-19 pandemic: a multicenter observational study.

This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episodes with a duration of untreated psychosis of less than 1 month and whose onset was related to the COVID-19 crisis were recruited, but only those patients meeting Diagnostic Statistical Manual 5th edition (DSM-5) criteria for "BPD with marked stressors" (DSM-5 code: 298.8) during follow-up were finally included. Patients' sociodemographic and clinical characteristics were collected at baseline and summarized with descriptive statistics. During the study period, 57 individuals with short-lived psychotic episodes related to the emotional stress of the COVID-19 pandemic were identified, of whom 33 met DSM-5 criteria for "BPD with marked stressors". The mean age was 42.33 ± 14.04 years, the gender distribution was almost the same, and the majority were rated as having good premorbid adjustment. About a quarter of the patients exhibited suicidal symptoms and almost half presented first-rank schizophrenia symptoms. None of them were COVID-19 positive, but in more than half of the cases, the topic of their psychotic features was COVID-19-related. The coronavirus pandemic is triggering a significant number of BPD cases. Their risk of suicidal behavior, their high relapse rate, and their low temporal stability make it necessary to closely monitor these patients over time.

Toward Understanding of Suicidality in a Spanish Clinical Population: Validation of the European Spanish Version of the Interpersonal Needs Questionnaire.

INTRODUCTION: Suicidal ideation (SI) represents one of the most prominent predictors of suicidal behavior (SB). The Interpersonal Needs Questionnaire (INQ) was developed from the Interpersonal Theory of Suicide (ITS) to assess the 2 core drivers of SI proposed by the theory. Despite the relevance of suicide-related ideations and ITS, there is a lack of psychometric measures validated in clinical Spanish population that adequately evaluate SI components of ITS. Thus, the main aim of the study was to validate INQ-10 in a Spanish clinical sample including the genuine cultural and linguistic characteristics of European Spanish. METHODS: 315 participants were included in the analyses; 149 of them consulted mental health services for the presence of suicide-related behaviors. A series of exploratory and confirmatory factor analyses were carried out to identify the factor solution. Bivariate and multivariate analyses were used to analyze psychometric properties. Finally, sensitivity and specificity properties were explored through receiver-operating characteristic analyses which also provided the cut-off values of the questionnaire. RESULTS: An 8-item version demonstrated a good fit to the 2-factor solution. Likewise, this 8-item version showed good psychometric properties. Sensitivity and specificity indices of the version validated as well as the calculated cut-off points were excellent. CONCLUSIONS: The current results demonstrate the utility of an 8-item INQ European Spanish version as a valid measure of the current SI in Spanish clinical population. In addition, the validated form reflects the theoretical framework on which it was built.

Metabolic syndrome in antipsychotic-naïve patients with first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general population is needed. METHODS: Studies on individuals with FEP defined as drug-naïve (0 days exposure to antipsychotics) were included to conduct a systematic review. A meta-analysis of proportions for the prevalence of MetS in antipsychotic-naïve patients was performed. Prevalence estimates and 95% CI were calculated using a random-effect model. Subgroup analyses and meta-regressions to identify sources and the amount of heterogeneity were also conducted. RESULTS: The search yielded 4143 articles. After the removal of duplicates, 2473 abstracts and titles were screened. At the full-text stage, 112 were screened, 18 articles were included in a systematic review and 13 articles in the main statistical analysis. The prevalence of MetS in naïve (0 days) FEP is 13.2% (95% CI 8.7-19.0). Ethnicity accounted for 3% of the heterogeneity between studies, and diagnostic criteria used for MetS accounted for 7%. When compared with controls matched by sex and age, the odds ratio is 2.52 (95% CI 1.29-5.07; p = 0.007). CONCLUSIONS: Our findings of increased rates of MetS in naïve FEP patients suggest that we are underestimating cardiovascular risk in this population, especially in those of non-Caucasian origin. Our findings support that altered metabolic parameters in FEPs are not exclusively due to antipsychotic treatments.

Predictors of diagnostic stability in brief psychotic disorders: Findings from a 3-year longitudinal study.

INTRODUCTION: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. METHODS: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria was explored in a large epidemiological cohort (n = 569) of non-affective first-episode psychosis (FEP) patients enrolled in a three-year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. RESULTS: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM-IV criteria for BPD, of whom 40 completed the three-year follow-up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. CONCLUSION: Our findings confirm that BPD is a clinical condition with moderate-to-low temporal stability and demonstrate that approximately two-thirds of FEP individuals experiencing BPD will develop a long-lasting psychotic disorder during follow-up, mainly schizophrenia.

Impaired motor cortical plasticity associated with cannabis use disorder in young adults.

Maladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20- 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans.

Predictors of diagnostic stability in acute and transient psychotic disorders: validation of previous findings and implications for ICD-11.

Acute and transient psychotic disorders (ATPD) have moderate prospective diagnostic stability. Female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features have been found to be predictive factors of diagnostic stability in ATPDs. Nevertheless, most of these findings need to be replicated. The purpose of this study was to evaluate the diagnostic stability of patients with ATPD, and to determine whether previously accepted predictors of diagnostic stability for ATPD could be externally validated in our cohort. To that end, a prospective 2-year observational study was conducted on patients with first-episode ATPD. Multivariate analysis was performed to determine factors associated with ATPD diagnostic stability at the end of the follow-up period. The following prior knowledge variables were analyzed: female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features. Sixty-eight patients with first-episode ATPD completed the follow-up, of whom 55.9% (n = 38) retained their diagnosis of ATPD at the end of the study. Multivariate analysis revealed that diagnostic stability was independently significantly associated with the presence of shifting polymorphic symptomatology (OR = 7.42, 95% CI 1.65-33.30; p = 0.009) and the absence of schizophrenic features (OR = 6.37, 95% CI 1.47-27.54; p = 0.013) at the onset of the psychotic disorder. Our findings provide empirical support for the ICD-11 proposal restricting the new ATPD category to the acute polymorphic disorder without schizophrenia symptoms.

The relationship with the voices as a dialogical experience: The role of self-focused attention and dissociation.

OBJECTIVE: The purpose of this article was to study the relationship of self-focused attention and dissociation with the dialogical relationship persons diagnosed with psychosis have with their voices. METHOD: The DAIMON Scale was applied to 62 persons diagnosed with psychosis to measure the dialogical relationship with their voices, and the Cambridge depersonalization scale, the Tellegen absorption scale, and the self-focused attention scale. RESULTS: The results showed that the dialogical relationship with the voices was associated with high levels of self-focused attention (private and public), depersonalization, and absorption. It was also found that absorption mediated significantly between public self-focused attention and the dialogical relationship with the voices. CONCLUSIONS: The role of dissociation and self-focused attention in forming the dialogical relationship a person with psychosis has with the voices is discussed and approaches to treatment are suggested.

Spanish validation of the self-evaluation of negative symptoms scale SNS in an adolescent population.

BACKGROUND: Negative symptoms (NS) may be observed in the general population in an attenuated form and in high-risk mental states. However, they have been less studied in the general population than positive symptoms, in spite of their importance at the insidious onset of schizophrenia and their appearance before positive symptoms. This study aimed to analyze the empirical structure of the Spanish version of the Self-Evaluation of Negative Symptoms (SNS) Scale and find its psychometric properties and invariance of measurement across sex and age in a sample of adolescents. METHODS: The sample consisted of 4521 adolescents (53.6% female) from 11 to 18 years of age. RESULTS: Confirmatory Factor Analysis of the SNS confirmed an internal structure of five first-order factors by the characteristic dimensions of NS: avolition, social withdrawal, diminished emotional range, anhedonia, alogia, and one second-order factor which includes the total NS score. Multi-group confirmatory factor analysis showed that the scale was invariant across sex and age. Total scale reliability was adequate. A strong relationship was found between the SNS with depressive symptomatology, moderate with ideas of reference and low with aberrant salience. CONCLUSION: The results back use of the Spanish version of the SNS scale for detection of NS in the general population of adolescents.

Childhood memories of threatening experiences and submissiveness and its relationship to hallucination proneness and ideas of reference: The mediating role of dissociation.

Recent studies have emphasized the importance of childhood memories of threatening experiences and submissiveness in a diversity of psychological disorders. The purpose of this work was to study their specific relationship with hallucination proneness and ideas of reference in healthy subjects. The ELES scale for measuring memory of adverse childhood experiences, the DES-II scale for measuring dissociation, the LSHS-R scale for measuring hallucination proneness, and the REF for ideas of reference were applied to a sample of 472 subjects. A positive association was found between childhood memories of adverse experiences and hallucination proneness and ideas of reference, on one hand, and dissociation on the other. A mediation analysis showed that dissociation was a mediator between the memory of adverse childhood experiences and hallucination proneness on one hand, and ideas of reference on the other. When the role of mediator of the types of dissociative experiences was studied, it was found that absorption and depersonalization mediated between adverse experiences and hallucination proneness. However, this mediating effect was not found between adverse experiences and ideas of reference. The relationship between these last two variables was direct. The results suggest that childhood memories of adverse experiences are a relevant factor in understanding hallucination proneness and ideas of reference. Similarly, dissociation is a specific mediator between adverse childhood experiences and hallucination proneness.

Trait- and state-dependent cortical inhibitory deficits in bipolar disorder.

OBJECTIVES: Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. METHODS: Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. RESULTS: During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. CONCLUSIONS: The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits.

One-year follow-up study of first suicide attempts in first episode psychosis: Personality traits and temporal pattern.

OBJECTIVES: The highest suicide rates occur after psychiatric hospitalization or soon after discharge. In addition to other factors, personality traits have been suggested as predictors of suicide attempts (SA) after first episode psychosis (FEP). In this study we examined their temporal pattern and the influence of personality traits on first suicide attempts (fSA) during one year after FEP. METHOD: One-year follow-up of 65 FEP patients. Bivariate and multivariable analyses were performed to explore the relationship between personality traits and fSA. This analysis was also adjusted for a set of sociodemographic, clinical and psychopathological variables. RESULTS: fSAs in the six months following FEP were predicted by higher scores in passive-dependent personality traits (OR = 2.42, 95% CI = 1.15-5.09) and severity of symptoms at onset (OR = 2.00, 95% CI = 1.07-3.76). Severity of symptoms at onset (OR = 2.71, CI = 1.15-6.39) was the most significant predictor of fSA from six to twelve months after FEP. Seventy percent of fSA occurred during the first six months after FEP, decreasing considerably afterwards. CONCLUSIONS: Our study suggests that personality traits play a role in fSA after FEP. Specifically, passive-dependent personality traits emerged as a predictor of fSA in the six months following FEP. Severity of symptoms at onset predicted early and late first suicide attempts. We also found that risk of fSA is highest during the six months following FEP. These results can contribute to the implementation of prevention program.