Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.

To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.

A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.

Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.

One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Schizotypal personality is a condition suffered by 4% of the population. It is defined by presenting interpersonal, behavioral and perceptual features similar to the clinical features of psychotic disorders, such as schizophrenia, in less intensity and dysfunctionality, but at risk of reaching psychosis.

Presentation of a clinical case about a patient with premorbid schizotypal personality traits presenting with an acute psychotic episode.

Literature review on association between schizotypal personality and psychosis.

A 57-year-old woman with a history of adaptive disorder due to work problems 13 years ago, currently without psychopharmacological treatment, goes to the emergency room brought by the emergency services due to behavioral alteration. She reports that “her husband and son wanted to sexually abuse her”, so she had to run away from home and has been running through the streets of the town without clothes and barefoot.

Her husband relates attitude alterations and extravagant behaviors of years of evolution, such as going on diets of eating only bread for 40 days or talking about exoteric and religious subjects, as believing that the devil got inside her husband through a dental implant. He reports that these behaviors have been accentuated during the last month. She has also created a tarot website, and has even had discussions with several users. She is increasingly suspicious of him, has stopped talking to him and stays in his room all day long, with unmotivated laughter and soliloquies.

It was decided to admit him to Psychiatry and risperidone 4 mg was started. At the beginning, she was suspicious and reticent in the interview. As the days went by, communication improved, she showed a relaxed gesture and distanced herself from the delirious ideation, criticizing the episode.

In recent years, there has been increasing interest in understanding the association between schizotypy and serious mental disorder. Several theories understand schizotypy as a natural continuum of personality that reveals genetic vulnerability and that can lead to psychotic disorder when added to precipitating factors. Other theories define schizotypy as a “latent schizophrenia” where symptoms are contained and expressed in less intensity.

Around 20% evolves to paranoid schizophrenia or other serious mental disorders. It is complex to distinguish between those individuals in whom schizotypy is a prodrome and those in whom it is a stable personality trait. To date, studies applying early psychotherapeutic or pharmacological interventions have had insufficient and contradictory results, and the follow-up and treatment of these individuals could be a stress factor and a stigma. Some studies are looking for reliable markers of evolution to schizophrenia in order to establish adequate protocols for detention, follow-up and treatment.

None Declared

Men and women with psychosis have different courses and presentations of symptoms. Men with psychosis have an earlier onset of illness, more negative symptoms, and worse premorbid functioning. Women, on the other hand, have better social functioning and less substance abuse. Despite these evident differences, there are few studies that delve into these distinctions, especially from a subjective perspective.

The aim of this study is to understand the differences in the perception of psychosis between men and women.

Five women and five men diagnosed with schizophrenia participated in the study. They were matched so that the age difference between them was no more than 5 years, with ages ranging from 40 to 56 years. Participants had not experienced acute decompensation of their underlying illness and had not required admission to an Acute Care Unit in the 6 months prior to inclusion in the study. Data collection was conducted through the Spanish translation of the Indiana Psychiatric Illness Interview, consisting of five parts: a narrative about their life, a narrative about the illness, questions related to how the illness has changed their life and what has not changed, the overall influence of the illness on their life, and lastly, expectations for the future.

Men expressed more concerns about work (4 men versus 2 women), while women expressed more concerns about not having become mothers (3 out of 5 women, compared to one man). All participants shared experiences of isolation in intimate relationships, including romantic relationships. Regarding stigma, three women believed that people treated them like children and dismissed their opinions. However, two of them viewed this behavior from their loved ones positively. Two women discussed the impact that psychosis and medications had on their bodies and how others had reacted to these changes

The concerns and stigma associated with mental illness differ between genders. These differences should be taken into account when developing specific biopsychosocial treatment plans.

None Declared

In recent years, research has focused on the older adults with bipolar disorder (OABD), aged 50 years and over, a constantly growing population due to the increased of life expectancy. Actually, some authors suggest that these individuals constitute a distinct subtype with a specific and different needs such as seen in epidemiologic, clinical and cognitive features. Further research has revealed significant differences between females and males with BD in clinical and cognitive variables in middle-aged and young patients, but this topic among OABD population remains unclear.

The aim of this study is to identify the distinctive profile in clinical, functional and neurocognitive variables between females and males in OABD.

A sample of OABD and Healthy Controls (HC) were included. Euthymic patients or in partial remission were included. Neurocognition was measured with a battery of tests that included premorbid intelligence quotient, working memory, verbal and visual memory, processing speed, language and executive functions. Independent t-test and Chi-squared test analysis were performed as appropriated.

According to the analysis, statistically significant differences were seen between females and males. A more impaired cognitive profile is observed in women. They performed worse in the subscales of Arithmetic (F= 6.728, p = <0.001), forward digits (F= 0.936, p= 0.019) and Total Digits (F= 1.208, p= 0.019) of the WAIS-III, in the Stroop Color Word Test, color reading (F= 0.130, p= < 0.001), in the Continuous Performance Test, block change measure (F= 2.059, p= 0.037), in the Rey-Osterrieth Complex Figure-copy (F= 0.005, p= 0.029) and in the Boston Naming Test (F= 0.011, p= 0.024). Nor significant differences were found in clinical neither in psychosocial functioning variables.

In view of the following results, and since no differences were observed between women and men in terms of clinical and functional outcomes, it could be said that the differences observed in cognition cannot be explained by disease-related factors. Furthermore, these results highlight the need to develop a gender-specific cognitive interventions in OABD population. In this way, we could have an impact on the course of the illness to reach a better quality of life.

S. Martín-Parra: None Declared, C. Torrent Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00344) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIIISubdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Ruiz: None Declared, M. Bort: None Declared, G. Fico Grant / Research support from: Fellowship from “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), V. Oliva: None Declared, M. Prisco: None Declared, J. Sanchez-Moreno Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), E. Jimenez Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Martinez-Aran: None Declared, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151), B. Sole: None Declared, L. Montejo: None Declared

Contrary to classical belief, people affected by this disease are at greater risk of developing organic pathologies.This risk has a very complex origin: a greater exposure to risk factors and specific socioeconomic conditions, a high prevalence of risk behaviors, the use of antipsychotics, and a potential common genetic background. (Reynolds et al.Int. J.Neuropsychopharmacol.2021; 24 854–855, Suvisaari J et al. Curr Diab Rep. 2016 16). Multiple studies demonstrate that Schizophrenia confers a high endogenous risk of Diabetes. Before patients diagnosed with Schizophrenia start taking antipsychotics (Andreassen OA et al. Am J Psychiatry. 2017;174 616-617), they have an approximately 3 times higher risk of developing Diabetes compared to the general population. The risk increases 3.6 times after the initiation of antipsychotic treatment compared to drug naive patients(Annamalai A et al World J Diabetes. 2017 390-396)

To study the association between Schizophrenia or other Psychotic Disorders and Diabetes Mellitus in a sample of patients diagnosed with Schizophrenia or other Psychotic Disorders.

This is a Descriptive and Cross-sectional Observational Study. Clinical Histories were reviewed and a personal or telephone interview was established to expand data related to the objectives of the study. The patients were recruited among the patients seen in the specific Severe Mental Disorder consultation who had a diagnosis of schizophrenia or other Psychotic Disorders, according to DSM 5-TR criteria.

From a sample of 93 patients, 24 had Diabetes. The Prevalence of Diabetes in patients with Schizophrenia or other Psychotic Disorders was 25.8%. Of the patients without a diagnosis of Diabetes, 15 of them had values of Glycosylated Hemoglobin (HbA1c) for Prediabetes. Using the Chi-Square Test, statistically significant differences were found between the variable Main Psychiatric Medication and Diabetes. Patients treated with Clozapine, Aripiprazole and Olanzapine had a Prevalence of Diabetes of 40.9%, 33.3% and 28.5%, respectively.

Prevalence of Diabetes in our sample was 3.4 times higher than the 7.51% of the general population in Spain. This presumes a significant importance and impact on the health of these patients. The diabetic patients in our sample were diagnosed with Diabetes years after the diagnosis of the mental illness, which seems to indicate that the causes have to do with lifestyle, dietary habits, weight, and exposure to chronic antipsychotics. Premature death in schizophrenia has several explanations, being of special importance the development of cardiovascular disorders and Diabetes This can be due to many reasons, but it is worth highlighting the metabolic side effects of some antipsychotics and lifestyle. In this sense, it is essential to carefully monitor this group of patients.

None Declared

Delusional parasitosis, also known as delusional infestation or Ekbom’s syndrome, is a rare psychotic disorder characterized by the false belief that a parasitic skin infestation exists, despite the absence of any medical evidence to support this claim. These patients often see many physicians, so a multidisciplinary approach among clinicians is important. Many patients refuse any treatment due to their firm belief that they suffer from an infestation, not a psychiatric condition, so it is crucial to gain the trust of these patients.

The comprehensive review of this clinical case aims to investigate Ekbom syndrome, from a historical, clinical and therapeutic perspective.

Literature review based on delusional parasitosis.

A 65-year-old woman comes to the psychiatry consultation referred by her primary care physician concerned about being infested by insects that she perceives through scales on her skin for the last three months. She recognizes important impact on her functionality. She is also convinced that her family is being infected too. As psychiatric history she recognizes alcohol abuse in the past (no current consumption) and an episode of persecutory characteristics with a neighbor, more than ten years ago. On psychopathological examination, she shows delusional ideation of parasitosis, with high behavioral repercussions, cenesthetic and cotariform hallucinations, as well as feelings of helplessness and anger. Treatment with Pimozide was started and the patient was referred to dermatology for evaluation, a plan she accepted. Her primary care physician and dermatology specialist were informed about the case and the treatment plan. In the recent reviews, the patient is calmer, however, despite the corroboration of dermatology and in the absence of organic lesions in cranial CT, she is still unsatisfied with the results, remaining firm in her conviction of infestation. It was decided to start treatment with atypical neuroleptics (Aripiprazole), with progressive recovery of her previous functionality.

Despite the increase in the number of studies in recent years, there are still few studies on this type of delirium. The female:male ratio varies in the bibiliography (between 2:1 and 3:1). The onset is usually insidious, generally appearing as a patient who comes to his primary care physician convinced of having parasites in different skin locations. It is usual to observe scratching lesions or even wounds in search of the parasite. In the past, the most used and studied treatment was Pimozide. Currently the treatment of choice is atypical neuroleptics due to their lower side effects. The latest reviews on the prognosis of this disorder show data with percentages of complete recovery between 51% and 70%, and partial responses between 16.5% and 20%. Finally, for a good diagnosis and therapeutic management, it is important to achieve a multidisciplinary approach.

None Declared

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.

In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).

Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

Behavioral (externalizing) and emotional (internalizing) problems were showed to be associated with the prenatal environment. Changes in placental DNA methylation was identified as a relevant potential mechanism of such association.

We aimed to explore the associations between placental DNA methylation and child behavior in order to explore pathways that could link prenatal exposures to child behavior.

Data including 441 children of 3 years of age from the EDEN mother-child cohort. Child behavior assessed using the Strengths and Difficulties Questionnaire (SDQ). Both hypotheses-driven and exploratory analyses (including epigenome-wide association studies (EWAS) and differentially methylated regions (DMR) analyses) were conducted. The analyses were adjusted for confounding and technical factors and estimated placental cell composition. All the p-values were corrected using a false discovery rate (FDR) procedure for multiple tests.

In the hypothesis-driven analysis, cg26703534 (AHRR), was significantly associated with emotional problems (pFDR = 0.03). In the exploratory analyses, cg09126090 (pFDR = 0.04) and cg10305789 (PPP1R16B; pFDR < 0.01) were significantly associated with peer-relationship problems and 33 DMRs were significantly associated with at least one of the SDQ subscales. Placental DNA methylation showed more associations with internalizing than externalizing symptoms, especially among girls. DMRs tented to include highly methylated CpGs.

This study investigated for the first time the associations between placental DNA methylation and internalizing and externalizing symptoms in preschoolers. Further analyses, such as consortium meta-analyses would be necessary to confirm and extend our results.

None Declared