Neuropsychological performance and disease burden in individuals at risk of developing Huntington disease.

INTRODUCTION: Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. OBJECTIVE: To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). METHOD: A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. RESULTS: Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. CONCLUSIONS: Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD.

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice.

Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.

Racial differences in pathways to care preceding first episode mania or psychosis: a historical cohort prodromal study.

Background: There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients. Methods: Using a comprehensive medical records linkage system (Rochester Epidemiology Project, REP), we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White). Results: A total of 205 (FEM = 74; FEP = 131) incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; p < 0.001) with an older age at time of first visit for a mental health complaint (15.7 ± 6.3 vs. 11.1 ± 6.0 years; p = 0.005). There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use. Conclusion: These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies.

Psychosocial factors associated with the risk of developing psychosis in a Mexican general population sample.

Epidemiological evidence has linked an array of sociodemographic and psychosocial factors with an increased risk of developing psychosis. However, research in samples from low- and middle-income countries is still scarce. This study used a Mexican sample to explore (i) sociodemographic and psychosocial differences between individuals with and without a positive screen for Clinical High-Risk for psychosis (CHR), and (ii) sociodemographic and psychosocial factors associated with screening positive for CHR. The sample consisted of 822 individuals from the general population who completed an online survey. Of the participants, 17.3% (n = 142) met the CHR screening criteria. Comparisons between those who screened positive (CHR-positive group) and those who did not (Non-CHR group) showed that participants in the CHR-positive group were younger, had a lower educational level, and reported more mental health problems than the Non-CHR group. Furthermore, relative to the Non-CHR group, the CHR-positive group had a greater prevalence of medium/high risk associated with cannabis use, a higher prevalence of adverse experiences (bullying, intimate partner violence, and experiencing a violent or unexpected death of a relative or friend), as well as higher levels of childhood maltreatment, poorer family functioning, and more distress associated with the COVID-19 pandemic. Groups did not differ in sex, marital/relationship status, occupation, and socio-economic status. Finally, when examined in multivariate analyses, the variables associated with screening positive for CHR were: having an unhealthy family functioning (OR = 2.75, 95%CI 1.69-4.46), a higher risk associated with cannabis use (OR = 2.75, 95%CI 1.63-4.64), a lower level of education (OR = 1.55, 95%CI 1.003-2.54), having experienced a major natural disaster (OR = 1.94, 95%CI 1.18-3.16), having experienced a violent or unexpected death of a relative or friend (OR = 1.85, 95%CI 1.22-2.81), higher levels of childhood emotional abuse (OR = 1.88, 95%CI 1.09-3.25), physical neglect (OR = 1.68, 95%CI 1.08-2.61), and physical abuse (OR = 1.66, 95%CI 1.05-2.61), and higher COVID-related distress (OR = 1.10, 95%CI 1.01-1.20). An older age was a protective factor for screening positive for CHR (OR = 0.96, 95%CI 0.92-0.99). Overall, the findings highlight the importance of examining potential psychosocial contributors to psychosis vulnerability across different sociocultural contexts to delineate risk and protective processes relevant to specific populations and better target preventive intervention efforts.

Adolescent nicotine potentiates the inhibitory effect of raclopride, a D2R antagonist, on phencyclidine-sensitized psychotic-like behavior in mice.

The association between schizophrenia and nicotine addiction becomes evident during adolescence. Here, to investigate interactive events that might underlie the early establishment of this comorbidity, we used phencyclidine-evoked locomotor sensitization, a proxy model of psychotic behavior, and nicotine minipump infusions in adolescent mice. Considering the involvement of dopamine D2 receptors in both schizophrenia and addiction, we further tested their role by exposing mice to raclopride. Adolescent mice that were either exposed to nicotine (24 mg/Kg/day) or not, received single daily raclopride (0.5 mg/kg, s.c.) or saline followed by phencyclidine injections (10 mg/Kg, s.c.) during open field testing for 6 consecutive days (Acquisition phase, ACQ). Phencyclidine and nicotine challenges (Sensitization Test, ST) were carried out after a 5-day withdrawal. Ambulation escalated in response to repeated phencyclidine exposure during ACQ and was increased after phencyclidine challenge, evidencing development and expression of locomotor sensitization. Raclopride prevented phencyclidine-evoked development of sensitization. However, raclopride pre-exposure during ACQ only shortened its expression in phencyclidine-challenged mice. Nicotine failed to interfere with phencyclidine stimulatory effects during ACQ but potentiated raclopride inhibition during the first ACQ days. During ST, nicotine history shortened the expression of phencyclidine-evoked sensitization. Nicotine challenge had no impact on locomotion, which is consistent with a lack of nicotine/phencyclidine cross-sensitization. In conclusion, our results show that nicotine does not worsen, and may even ameliorate phencyclidine-sensitized psychotic-like behavior in adolescent mice. The potentiation of raclopride-mediated inhibition further suggests that nicotine transiently improves the therapeutic efficacy of medication on psychotic symptoms through mechanisms that converge on D2 receptors.

Motor Dysfunction as a Prodrome of Parkinson's Disease.

BACKGROUND: Recognition of motor signs in the prodromal stage could help identify those at risk of developing Parkinson's disease (PD). OBJECTIVE: This study identified motor symptoms and signs in individuals suspected of having PD but who did not have a progressive reduction in the speed and amplitude of finger tapping or other physical signs indicative of bradykinesia. METHODS: 146 patients, who had symptoms or signs suggestive of PD, were serially evaluated by a movement disorder specialist, using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and video recordings. If the patients 'converted' to PD during follow-up, they were categorized as cases and compared with those who did not meet PD criteria during follow-up (non-cases). RESULTS: The 82 cases were more likely to have action dystonia or postural/action/rest tremor of a limb (OR 2.8; 95% CI 1.1-7.1; p = 0.02), a reduced blink rate at rest (OR 2.3; 95% CI 1.2-4.6; p = 0.01), anxiety (OR 8.9; 95% CI 2.6-31.1; p < 0.001), depression (OR 7.0; 95% CI 2.9-17.2; p < 0.001), or a frozen shoulder (OR 3.1; 95% CI 1.6-6.2) than the 64 'non-cases'.A reduction of the fast blink rate was common in patients who met the criteria for PD (p < 0.001). CONCLUSIONS: This study emphasizes that motor dysfunction is a component of the clinical prodrome seen in some patients with PD.

The importance of semiological information based on epileptic seizure history.

Semiology is the backbone of any correct categorization of seizures, as epileptic or not, focal or bilateral, and is fundamental to elucidating how they are anatomically generated in the brain. An anatomical hypothesis derived from seizure history is the precondition for optimally designed ancillary studies. Without understanding seizure semiology, no rational therapy is possible. This article describes the semiological approach using patient history based on full use of patients' self-reports as well as descriptions by witnesses. Auras represent the subjective aspects of seizures and provide important semiological clues as observable signs, sometimes including rather precise direct anatomical information. Methods of extracting, facilitating and analysing self-reports including linguistic conversation analysis are presented in detail. It is highlighted that prodromes, seizure triggers and reflex epileptic mechanisms can provide crucial information for diagnostics and therapy. Special issues considering seizure semiology in children are discussed in a separate section. Other sections are dedicated to the two most important issues of differential diagnosis: how to distinguish (1) focal from "generalized" epilepsies, particularly when focal seizure phenomena appear in a bilateral epilepsy; and (2) epileptic from a series of non-epileptic events.

Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?

Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use.

Clinical characteristics and influence of childhood trauma on the prodrome of bipolar disorder

Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.

Anomalías de la experiencia subjetiva en psicosis: Concepto y validación empírica del modelo de los Síntomas Básicos / Anomalies of subjective experience in psychosis: Concept and empirical validation of the Basic Symptoms model

Introducción Tradicionalmente, en la investigación, el diagnóstico y el tratamiento de los trastornos del espectro psicótico ha imperado un modelo de comprensión objetivista, centrado principalmente en los síntomas positivos y negativos. Aunque es innegable el valor de esta aproximación, implica considerables limitaciones ampliamente conocidas. De forma complementaria, existe una larga y prometedora tradición fenomenológica en la cual la experiencia subjetiva del síntoma del paciente adquiere una importancia fundamental. La aproximación de las anomalías de la experiencia subjetiva o, específicamente, de los Síntomas Básicos ha adquirido mucha fuerza dentro del contexto de detección precoz de psicosis y esquizofrenia. Objetivo Esta revisión expone la aproximación fenomenológica de las anomalías de la experiencia subjetiva y se define detalladamente el modelo de los Síntomas Básicos, así como su proceso de validación empírica en el campo de detección precoz de psicosis. Método Las bases de datos consultadas han sido PubMed Central® y PsycINFO®, así como libros de autores de referencia. Resultados En las dos últimas décadas ha habido un creciente interés científico sobre esta orientación con resultados muy prometedores. Discusión y conclusión El modelo más destacado a nivel empírico es el de los Síntomas Básicos, aunque recientemente también han ganado gran relevancia las alteraciones del flujo de la consciencia o del self. Se ha comprobado que las anomalías de la experiencia subjetiva consiguen delimitar un perfil de riesgo de psicosis más temprano que los síntomas psicóticos atenuados. Por tanto, son un complemento altamente válido en las estrategias de detección e intervención temprana de psicosis.

Introduction Research, diagnosis and treatment of psychotic spectrum disorders have been traditionally dominated by an objectivist approach to their understanding, being primarily focused on positive and negative symptoms. The value of this approach goes without question, but it also involves considerable and widely known limitations. From a complementary perspective, there is a longstanding and promising phenomenological tradition in which the subjective experience of the patient's symptom becomes crucial. The focus on the anomalies of subjective experience, or the Basic Symptom concept specifically, has gained much momentum in the context of early detection of psychosis and schizophrenia. Objective This review presents the phenomenological approach to the anomalies of subjective experience and the Basic Symptoms model and its empirical validation process in the field of early detection of psychosis. Method The scientific literature was collected from PubMed Central® and PsyclNFO® databases and books from authors of reference. Results In the last two decades there has been a growing scientific interest in this approach with very promising results. Discussion and conclusion The most prominent model from an empirical standpoint is the Basic Symptoms approach, although recently the disturbances of the flow of consciousness or self disorders have achieved great relevance as well. It has been found that the anomalies of subjective experience could delimitate a risk profile that precedes that defined by attenuated psychotic symptoms. Therefore, this approach is a highly valuable complement in the early detection and intervention of psychosis strategies.