Ion channel dysregulation and cellular adaptations to alpha-synuclein in stressful pacemakers of the parkinsonian brainstem.

Parkinson's disease (PD) is diagnosed by its cardinal motor symptoms that are associated with the loss of dopamine neurons in the substantia nigra pars compacta (SNc). However, PD patients suffer from various non-motor symptoms years before diagnosis. These prodromal symptoms are thought to be associated with the appearance of Lewy body pathologies (LBP) in brainstem regions such as the dorsal motor nucleus of the vagus (DMV), the locus coeruleus (LC) and others. The neurons in these regions that are vulnerable to LBP are all slow autonomous pacemaker neurons that exhibit elevated oxidative stress due to their perpetual influx of Ca2+ ions. Aggregation of toxic α-Synuclein (aSyn) - the main constituent of LBP - during the long prodromal period challenges these vulnerable neurons, presumably altering their biophysics and physiology. In contrast to pathophysiology of late stage parkinsonism which is well-documented, little is known about the pathophysiology of the brainstem during prodromal PD. In this review, we discuss ion channel dysregulation associated with aSyn aggregation in brainstem pacemaker neurons and their cellular responses to them. While toxic aSyn elevates oxidative stress in SNc and LC pacemaker neurons and exacerbates their phenotype, DMV neurons mount an adaptive response that mitigates the oxidative stress. Ion channel dysregulation and cellular adaptations may be the drivers of the prodromal symptoms of PD. For example, selective targeting of toxic aSyn to DMV pacemakers, elevates the surface density of K+ channels, which slows their firing rate, resulting in reduced parasympathetic tone to the gastrointestinal tract, which resembles the prodromal PD symptoms of dysphagia and constipation. The divergent responses of SNc & LC vs. DMV pacemaker neurons may explain why the latter outlive the former despite presenting LBPs earlier. Elucidation the brainstem pathophysiology of prodromal PD could pave the way for physiological biomarkers, earlier diagnosis and novel neuroprotective therapies for PD.

The experience sampling methodology in psychosis risk states: A systematic review.

The experience sampling method (ESM) is a structured diary technique, which is used to assess thoughts, mood and appraise subjective experiences in daily life. It has been recognized as a useful tool for understanding the characteristics, dynamics, and underlying mechanisms of prodromal symptoms of psychosis. The present systematic review aimed to provide a qualitative synthesis of findings provided by the ESM studies conducted in people with psychosis risk states. A systematic review of the MEDLINE, ERIC, Academic Search Ultimate, and Health Source: Nursing/Academic Edition databases, utilizing search terms related to the ESM and the risk of psychosis was conducted. Out of 1069 publication records identified, 77 studies met the inclusion criteria for the review. Data were synthesized around the following topics: 1) assessment of symptoms dynamics and social functioning; 2) assessment of the mechanisms contributing to the emergence of psychotic experiences and 3) assessment of stress sensitivity. The studies have shown that negative emotions are associated with subsequent development of paranoia. The tendency to draw hasty conclusions, aberrant salience, self-esteem, and emotion regulation were the most frequently reported mechanisms associated with the emergence of psychotic experiences. Studies using the ESM also provided evidence for the role of stress sensitivity, in the development of psychotic symptoms. The ESM has widely been applied to studies investigating psychosis risk states, using a variety of protocols. Findings from this systematic review might inform future studies and indicate potential targets for interventions.

Prodromal questionnaire (PQ-16) dimensionality among Colombian adolescent school students.

AIMS: The study aimed to determine the dimensionality of the Spanish version of the PQ-16 among Colombian adolescent school students. METHODS: A validation study was designed with the participation of 334 Colombian adolescent students aged between 13 and 17 (M = 15.2, SD = 1.1); 171 (52.1%) were girls, and 163 (47.9%) were boys, 229 (68.6%) were ninth-grade students and 105 (31.4%) were tenth-grade students. Confirmatory factor analysis was performed, internal consistency was calculated with the Kuder-Richardson and McDonald's omega tests, and correlation with suicide ideation was computed with the Kendall correlation (r). RESULTS: The confirmatory factor analysis showed that the PQ-16 adequately fit a unidimensional structure: RMSEA = 0.05 (90%CI 0.04-0.06), CFI = 0.91, TLI = 0.90, SRMR = 0.05, chi-squared = 193.18 (df = 102, p < 0.001) and normalized chi-squared = 1.89. This factor presented high internal consistency: Kuder-Richardson test and McDonald's omega of 0.83. The correlation between the PQ-16 and suicide ideation was r = 0.45 (p < 0.001). CONCLUSION: The PQ-16 is a one-dimensional tool with high internal consistency and correlation with suicide ideation among schooled adolescents. Further research should explore the PQ-16 performance against a structured clinical interview.

Study of the different sleep disturbances during the prodromal phase of depression and mania in bipolar disorders.

BACKGROUND: One of the challenges in bipolar disorder (BD) lies in early detection of the illness and its recurrences, to improve prognosis. Sleep disturbances (SD) have been proposed as reliable predictive markers of conversion. While preliminary studies have explored the relationship between SD and the onset of mood episodes, the results remain heterogeneous and a few have specifically examined patients' perception of prodromal symptoms and their progression until the episode occurs. Identifying prodromes represents a crucial clinical challenge, as it enables early intervention, thereby reducing the severity of BD. Therefore, the objective of this study is to better characterize and evaluate the progressive nature of SD as prodromal symptoms of mood episodes, and patients' perception of it. METHODS: Patients diagnosed with BD, either hospitalized or seeking treatment for a (hypo)manic or depressive episode benefited from standardized questionnaires, structured interviews, and self-report questionnaires to evaluate SD prior to the current episode, as well as sociodemographic and clinical information. RESULTS: Out of the 41 patients included, 59% spontaneously reported SD prior to the episode, appearing 90 days before depression and 35 days before mania (pre-indexed/spontaneous reports: 51.22% insomnia complaints, 4.88% hypersomnolence complaints, 7.32% parasomnias, 2.44% sleep movements). After inquiry about specific SD, the percentage of patients reporting prodromal SD increased significantly to 83%, appearing 210 days before depression and 112.5 days before mania (post-indexed reports: 75.61% presented with insomnia complaints appearing 150 days before depression and 20 days before mania, 46.34% had hypersomnolence complaints appearing 60 days before depression, 43.9% had parasomnias appearing 210 days before depression and 22.5 days before mania, 36.59% had sleep movements appearing 120 days before depression and 150 days before mania). Of note, bruxism appeared in 35% of patients before mania, and restless legs syndrome in 20% of patients before depression. CONCLUSION: This study highlights the very high prevalence of SD prior to a mood episode in patients with BD with differences between depressive and manic episodes. The more systematic screening of sleep alterations of the prodromal phase improved the recognition and characterization of different symptoms onset by patients. This underscores the need for precise questioning regarding sleep patterns in patients, to better identify the moment of transition toward a mood episode, referred to as "Chronos syndrome". The study emphasizes the importance of educating patients about the disorder and its sleep prodromal symptoms to facilitate early intervention and prevent recurrences.

Identifying prior signals of bipolar disorder using primary care electronic health records: a nested case-control study.

BACKGROUND: Bipolar disorders are serious mental illnesses, yet evidence suggests that the diagnosis and treatment of bipolar disorder can be delayed by around 6 years. AIM: To identify signals of undiagnosed bipolar disorder using routinely collected electronic health records. DESIGN AND SETTING: A nested case-control study conducted using the UK Clinical Practice Research Datalink (CPRD) GOLD dataset, an anonymised electronic primary care patient database linked with hospital records. 'Cases' were adult patients with incident bipolar disorder diagnoses between 1 January 2010 and 31 July 2017. METHOD: The patients with bipolar disorder (the bipolar disorder group) were matched by age, sex, and registered general practice to 20 'controls' without recorded bipolar disorder (the control group). Annual episode incidence rates were estimated and odds ratios from conditional logistic regression models were reported for recorded health events before the index (diagnosis) date. RESULTS: There were 2366 patients with incident bipolar disorder diagnoses and 47 138 matched control patients (median age 40 years and 60.4% female: n = 1430/2366 with bipolar disorder and n = 28 471/47 138 without). Compared with the control group, the bipolar disorder group had a higher incidence of diagnosed depressive, psychotic, anxiety, and personality disorders and escalating self-harm up to 10 years before a bipolar disorder diagnosis. Sleep disturbance, substance misuse, and mood swings were more frequent among the bipolar disorder group than the control group. The bipolar disorder group had more frequent face-to-face consultations, and were more likely to miss multiple scheduled appointments and to be prescribed ≥3 different psychotropic medication classes in a given year. CONCLUSION: Psychiatric diagnoses, psychotropic prescriptions, and health service use patterns might be signals of unreported bipolar disorder. Recognising these signals could prompt further investigation for undiagnosed significant psychopathology, leading to timely referral, assessment, and initiation of appropriate treatments.

Adapting the early recognition inventory ERIraos to Estonian: A validation study.

AIM: Validated assessment tools are needed to identify clinically high risk for psychosis. This study aimed to validate the early recognition inventory ERIraos, which consists of the ERIraos Checklist for risk screening and the ERIraos Symptom List for a more thorough risk assessment in the Estonian language to detect psychotic prodromal symptoms. METHODS: A prospective cohort study provided an opportunity to evaluate the characteristics of the ERIraos instrument in predicting the increased risk of a psychotic disorder in the future. The 177 study participants, aged 13-42 years old, were divided into groups without an increased risk and three risk groups with different risk severity levels based on the ERIraos Symptom List assessment. RESULTS: The results indicated excellent inter-rater reliability for the ERIraos Symptom List total score. The ability of the ERIraos checklist to screen persons with an elevated psychosis risk was very good (ROC-AUC = 0.86). The capability of the ERIraos Symptom List scores to predict the probability of transitioning to psychosis within 2 years was very good (ROC-AUC = 0.83). Brief limited intermittent psychotic symptoms and observable behavioural and affective symptoms were statistically significant predictors of transition to psychosis. There were strong and statistically significant correlations between the ERIraos Symptom List scores and other clinical measures assessing functioning and psychopathology. CONCLUSIONS: The results of this study demonstrate the reliability and validity of the Estonian version of the ERIraos instrument and support the usability of ERIraos as a two-step tool for the early recognition of psychosis risk.

Intensity of Psychoactive Substance Use Affects the Occurrence of Prodromal Symptoms of Psychosis.

BACKGROUND: Psychosis is defined as a series of symptoms that impair the mind and lead to a kind of loss of reference to reality. Development of psychosis is usually preceded by the appearance of prodromal symptoms. Numerous attempts have been made to find out how psychoactive substances can influence the onset and development of psychotic disorders, but to date there are no studies that show a link between the onset of prodromal symptoms and the use of psychoactive substances. METHODS: A survey consisting of epidemiological and demographic questions, the Drug Use Disorders Identification Test (DUDIT), and the Prodromal Questionnaire Brief Version (PQ-B) was conducted on social media among users of illegal psychoactive substances, covering 703 study participants. RESULTS: A total of 39.8% of the respondents had been treated by a psychiatrist, and the most popular drugs used by respondents in their lifetime were tetrahydrocannabinol-containing products, MDMA, amphetamines, and LSD. A significant correlation was found between the DUDIT and the PQ-B values. CONCLUSIONS: Intensity of psychoactive substance use correlated positively with the risk of appearance and intensity of prodromal symptoms of psychosis. Early exposure to psychoactive substances increased the risk of heavy substance use in adulthood and led to more frequent prodromal states.

Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease.

Neurodegenerative diseases are an increasingly common group of diseases that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer's disease (AD) and Parkinson's disease (PD) are the major disorders that lead to mild to severe cognitive and physical impairment and dementia. Interestingly, those diseases may show onset of prodromal symptoms early after middle age. Commonly, the evaluation of these neurodegenerative diseases is based on the detection of biomarkers, where functional and structural magnetic resonance imaging (MRI) have shown a central role in revealing early or prodromal phases, although it can be expensive, time-consuming, and not always available. The aforementioned diseases have a common impact on the visual system due to the pathophysiological mechanisms shared between the eye and the brain. In Parkinson's disease, α-synuclein deposition in the retinal cells, as well as in dopaminergic neurons of the substantia nigra, alters the visual cortex and retinal function, resulting in modifications to the visual field. Similarly, the visual cortex is modified by the neurofibrillary tangles and neuritic amyloid ß plaques typically seen in the Alzheimer's disease brain, and this may reflect the accumulation of these biomarkers in the retina during the early stages of the disease, as seen in postmortem retinas of AD patients. In this light, the ophthalmic evaluation of retinal neurodegeneration could become a cost-effective method for the early diagnosis of those diseases, overcoming the limitations of functional and structural imaging of the deep brain. This analysis is commonly used in ophthalmic practice, and interest in it has risen in recent years. This review will discuss the relationship between Alzheimer's disease and Parkinson's disease with retinal degeneration, highlighting how retinal analysis may represent a noninvasive and straightforward method for the early diagnosis of these neurodegenerative diseases.

The Italian version of the 16-item Prodromal Questionnaire (PQ-16) and its psychometric features in help-seeking ultra-high-risk subjects and in the general population.

BACKGROUND: Increasing attention to the early stages of psychosis and the identification of symptomatic prodromal states have led to the development of a growing number of screening tools. The 16-item version of the Prodromal Questionnaire (PQ-16) is a worldwide used self-administered tool for this purpose. However, to date, fundamental psychometric properties of PQ-16 were not thoroughly investigated. This study aimed to examine the structural validity, measurement invariance, reliability and other psychometrical properties of the Italian version of the PQ-16 (iPQ-16) in help-seeking individuals and in the general population. METHODS: The iPQ-16 was administered to 449 young outpatients attending six community mental health services and to 318 control participants enrolled in educational environment. Confirmatory factor analyses (CFAs), measurement invariance (MI) between the help-seeking group and the general population sample, convergent validity, test-retest reliability, internal consistency, and prevalence analyses were performed. Lastly, the validity of the adopted PQ-16 cut-offs through Receiver Operating Characteristic (ROC) curves plotted against CAARMS diagnoses was also tested. RESULTS: CFAs confirmed the single-factor structure for the iPQ-16 and scalar MI was reached. The iPQ-16 showed high internal consistency, test-retest reliability, convergent validity, and acceptable diagnostic accuracy. ROC analysis suggested a score of ≥4 as best cut-off. CONCLUSIONS: The iPQ-16 represents a valid and reliable questionnaire for the assessment of high mental risk in both Italian outpatients and general student population. It has good psychometric properties and is easy to implement as UHR screening for clinical as well as research purposes.

Impact of prodromal symptoms on the prognosis of patients with basilar artery occlusion treated with mechanical thrombectomy.

INTRODUCTION: Even with reperfusion therapies, the prognosis of patients with basilar artery occlusion (BAO) related stroke remains poor. We aimed to test the hypothesis that the presence of prodromal symptoms, an easily available anamnestic data, is a key determinant of poor functional outcome. PATIENTS AND METHODS: Data from patients with BAO treated in Lille, France, with mechanical thrombectomy (MT) between 2015 and 2021 were prospectively collected. The presence of prodromal symptoms was defined by previous transient neurological deficit or gradual progressive clinical worsening preceding a secondary sudden clinical worsening. We compared the characteristics of patients with and without prodromal symptoms. We built multivariate logistic regression models to study the association between the presence of prodromal symptoms and functional (mRS 0-3 and mortality), and procedural (successful recanalization and early reocclusion) outcomes. RESULTS: Among the 180 patients, 63 (35%) had prodromal symptoms, most frequently a vertigo. Large artery atherosclerosis was the predominant cause of stroke (41.3%). The presence of prodromal symptoms was an independent predictor of worse 90-day functional outcome (mRS 0-3: 25.4% vs 47.0%, odds ratio (OR) 0.39; 95% confidence interval (CI) 0.16-0.86) and 90-day mortality (OR 2.17; 95% CI 1.02-4.65). Despite similar successful recanalization rate, the proportion of early basilar artery reocclusion was higher in patients with prodromal symptoms (23.8% vs 5.6%, p = 0.002). DISCUSSION AND CONCLUSION: More than one third of BAO patients treated with MT had prodromal symptoms, especially patients with large-artery atherosclerosis. Clinicians should systematically screen for prodromal symptoms given the poor related functional outcome and increased risk of early basilar artery reocclusion.

Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.

Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.

Symptoms and age of prodromal Alzheimer's disease in Down syndrome: a systematic review and meta-analysis.

The diagnostic criteria for adult-onset Alzheimer's disease (AD) in patients with Down syndrome (DS) have not been standardised. This study investigated the specific symptoms of AD in the prodromal stage of DS, the mean age at diagnosis at each stage of dementia, and the relationship between intellectual disability (ID) and dementia. PubMed, Web of Science, and Embase were searched for studies on DS, AD, early-stage disease, initial symptoms, and prodromal dementia registered between January 2012 and January 2022. We also performed a meta-analysis of the differences between the mean age at prodromal symptoms and AD diagnosis and the proportion of mild cognitive impairment in patients with mild and moderately abnormal ID. We selected 14 articles reporting the behavioural and psychological symptoms of dementia (BPSD) and memory- and language-related impairments as early symptoms of AD in patients with DS. The specific symptoms of BPSD were classified into five categories: irritability (agitation), apathy, abnormal behaviour, adaptive functioning, and sleep disturbance. The mean age at the diagnosis of prodromal symptoms and AD dementia was 52.7 and 56.2 years, respectively (mean difference, + 3.11 years; 95% CI 1.82-4.40) in the meta-analysis. The diagnosis of mild dementia tended to correlate with ID severity (odds ratio [OR], 1.38; 95% CI 0.87-2.18). The features of behaviour-variant frontotemporal dementia may be clinically confirmed in diagnosing early symptoms of DS-associated AD (DSAD). Moreover, age-appropriate cognitive assessment is important. Further studies are required to evaluate DSAD using a combination of biomarkers and ID-related data.

[Juvenile depression as at-risk state for psychotic disorders]. / Yunosheskie depressii kak gruppa riska endogennykh psikhozov.

OBJECTIVE: To establish the risk of psychotic disorders in juvenile depression and to study the role of negative symptoms in its formation. MATERIAL AND METHODS: Seventy-four in-patients (19.6±2.3 years old), who were hospitalized for the first time in the clinic for a depressive episode, were examined. Psychometric scales HDRS, SOPS, SANS were used. The risk of manifestation of psychotic disorders was established in the presence of attenuated positive symptoms (APS) with values of at least one of the points P1, P2, P3 and P4 of the corresponding SOPS subscale more or equal to 3. The overall risk of schizophrenia spectrum disorders was established in the presence of attenuated negative symptoms (ANS) with values of at least one of the points H1-H6 of the negative SOPS subscale is more than or equal to 5. Statistical analysis was carried out using the Statistica 12 program. RESULTS: During the psychometric assessment of patients at admission, four groups were identified based on the presence of APS and ANS: group 1 (APS+ANS), group 2 (APS), group 3 (ANS) and a comparison group without APS/ANS. It was found that the presence of APS and ANS in the structure of depression increased its severity (U=109.0; p=0.009). Assessment of the ANS severity on the negative subscale of SOPS and on the SANS demonstrated quantitative differences with the highest representation of negative symptoms in the corresponding groups (APS+ANS and ANS) with significant differences in total scores in the comparison group (U=93.0; p=0.004 and U=85.0; p=0.002). When studying the structure of negative symptoms according to the SANS subscales, patients with APS differed in a lower degree of severity of negative symptoms only according to the «Avolition-Apathy¼ subscale (U=141.5; p=0.028). Patients from the comparison group, despite significant differences in other psychopathological symptoms, showed lower values only for the SANS subscales «Affective flattening¼ (U=112.0; p=0.02) and, to a greater extent, «Avolition-Apathy¼ (U=84.0; p=0.002). CONCLUSION: Based on the presence of prodromal symptoms in the structure of juvenile depression and their dynamics during therapy, one can assume not only a different degree of risk of endogenous psychoses, but also their nosological affiliation.

Gender disparities in the mediating role of symptom knowledge level in reducing acute coronary syndrome (ACS) decision delay: Findings from a community-based study in China.

BACKGROUND: Implementing training programs to educate patients on the prodromal symptoms of acute coronary syndrome (ACS) may assist patients in accurately recognizing these symptoms, and ultimately decrease their time delay in seeking emergency medical services (EMS). However, the effectiveness of this approach remains uncertain, particularly among the Chinese population. METHODS: A cross-sectional study was conducted within 22 communities in Beijing, China between 2015 and 2018, with a total of 1099 participants recruited. The study utilized a standardized questionnaire to evaluate the presence of intentional decision delay in turning to EMS under a hypothetical chest pain, the participants' knowledge of ACS prodromal symptoms, and whether they had ever received any training programs aimed at increasing their symptom knowledge. Mediation analysis was performed with regression models and bootstrapping methods, and gender difference was further analyzed through moderated mediation analysis. RESULTS: A total of 1099 participants (58.2% female, median [IQR] age 34 [20]) were included in the study. The results of the mediation analysis indicated that training programs were associated with a decrease risk in decision delay, with increased knowledge playing a mediating role (mediation effect/total effect = 36.59%, P < 0.0001). Gender modified this mediation effect, with it being observed only in the male group. Specifically, training programs were not found to significantly decrease decision delay among females (P > 0.05), even though they did improve women's knowledge of ACS prodromal symptoms (ß = 0.57, P = 0.012). CONCLUSION: The results suggested a relationship between prior training programs and reduced decision delay, with increased knowledge of prodromal symptoms of ACS serving as a mediator. However, the effect was only observed in male participants and not in female participants. This highlights the notion that mere transfer of knowledge regarding ACS prodromal symptoms may not be sufficient to mitigate decision delay in the female population. Further research is needed to corroborate these results and to gain deeper insights into the gender-specific barriers encountered in this study.

Diglossia Correlates With Prodromal Symptoms of Psychosis Among First-Generation Migrants.

Background and Hypothesis: We have previously hypothesized that diglossia may be a risk factor for psychosis, drawing from observations on migration, ethnicity, social adversity, and language disturbances among others. However, empirical data on this association and the tools necessary for its measurement are limited. Study Design: In a cross-sectional online sample of first-generation migrants residing in majority English-speaking countries, a response-based decision tree was introduced to classify the sociolinguistic profiles of 1497 participants as either with or without diglossia. Using multivariate logistic regression, the association of diglossia with psychosis risk screening outcomes in the Prodromal Questionnaire-16 was calculated, adjusting for demographic and linguistic confounders. Differences in the symptom categories endorsed between the 2 groups were also examined. Study Results: Diglossia was identified in 18.4% of participants and was associated with an adjusted odds ratio of 2.58 for a positive risk screening outcome. Other significant factors included subjective social status, hearing difficulty, age, sex, country of residence, education level, and cannabis consumption. The effects of ethnicity, age at migration, fluency, relationship, and employment status were no more significant in the multivariate model. Finally, the largest differences in the proportion of positively responding participants between the two groups were found in symptoms relating to thought insertion and thought broadcasting. Conclusions: In a sociolinguistic hierarchical framework, diglossia is correlated with prodromal symptoms of psychosis in first-generation migrants.

The Effect of Untreated Illness in Youth Depression: A Cross-Sectional Study.

BACKGROUND: The existing research has mainly focused on exploring how the duration of untreated psychosis effects the further course of the disease. By contrast, the duration of an untreated illness (DUI) in youth depression and its impact on the further course of the disease has remained scarcely investigated. AIM: The current study aims to determine how the duration of untreated illness affects the severity of the symptoms during the first depressive episode and the degree to which the symptoms are reduced after treatment. METHODS: Fifty-two young male patients (15-29 years old) were examined. First, they were hospitalized with a severe without psychotic symptoms (F32.2) and moderate (F32.1) depressive episode. The Hamilton Depression Rating Scale (HDRS), the Scale of Prodromal Symptoms (SOPS), and the Scale for Assessment of Negative Symptoms (SANS) were used to achieve the research goals. The examination was conducted twice at the time of patient admission to the hospital and before discharge. Our statistical analysis was carried out with the Statistica 12 software. The Mann-Whitney U test was used to compare the differences between two independent groups. The Spearman's rank correlation coefficient was used to uncover any correlation between how long the illness has remained untreated and the severity of its clinical symptoms. RESULTS: All patients were hospitalized at the first depressive episode. The average duration of an untreated illness was 35.8±17.0 months. The patients were divided into two groups: the first group (59.6%, n=31), with a duration of the untreated illness of more than 36 months, and the second group (40.4%, n=21), with a duration of the untreated illness of less than 36 months. A cross-group comparison between the participants showed that the reduction of HDRS scores was significantly higher in the second group (p=0.019) at the time of discharge, with no differences in the severity of depressive symptoms (p=0.544) at the time of admission. Comorbidity was detected in 83.9% of the patients in the first group and in 42.9% of the patients in the second group. A greater therapy effectiveness was found to exist in the second group, as the depressive symptoms score on the HDRS scale (p=0.016; U=196.0) and prodromal symptoms score on the SOPS disorganization subscale (p=0.046; U=218.0) were found to have been reduced significantly. CONCLUSION: The study showed that DUI has an impact on the reduction of depressive, negative symptoms and symptoms of disorganization in youth patients at the first depressive episode. A high level of comorbidity has been uncovered, confirming that a variety of non-psychotic and psychotic disorders in youth manifest themselves in depression at a prodromal stage, causing difficulties in establishing diagnoses and requiring subsequent verification. Future research might need to focus on exploring depressive symptoms as predictors of mental disorders in youth patients.

Psychotic and affective symptoms of early-onset bipolar disorder: an observational study of patients in first manic episode

Objective: Presence of psychotic symptoms seems to be a commonplace in early-onset bipolar disorder (BD). However, few studies have examined their occurrence in adolescent-onset BD. We sought to investigate the frequency of affective and psychotic symptoms observed during the first manic episode in adolescents. Methods: Forty-nine adolescents with bipolar I disorder (DSM-IV criteria) were admitted to a psychiatric hospital during their first acute manic episode. Assessment for current psychiatric diagnosis was performed by direct clinical interview and the DSM-IV version of the Diagnostic Interview for Children and Adolescents (DICA). Results: Teenage inpatients with BD consistently exhibited typical manic features, such as euphoria, grandiosity, and psychomotor agitation. In addition, disorganization and psychotic symptoms were present in 82 and 55% of the total sample, respectively. There was no significant difference in symptoms between early- and late-adolescent subgroups. Remarkably, most patients (76%) reported previous depressive episode(s); of these, 47% had prominent psychotic features in the prior depressive period. Conclusion: These findings suggest that disorganization and psychotic symptoms during the first manic episode are salient features in adolescent-onset BD, and that psychotic depression frequently may precede psychotic mania. Nevertheless, differential diagnosis with schizophrenia should be routinely ruled out in cases of early-onset first psychotic episode.

Úlcera de Lipschütz: reporte de un caso y revisión bibliográfica / Lipschütz Ulcer: a case report and a literature review

Resumen: ANTECEDENTES: Las úlceras de Lipschütz son lesiones vulvovaginales dolorosas, de aparición aguda y desaparición espontánea en 2 a 6 semanas, no dejan secuelas ni son recurrentes a largo plazo. Su etiopatogenia es incierta, alrededor de 70% se consideran idiopáticas. En los estudios más recientes se ha demostrado su asociación con agentes infecciosos, sobre todo con el virus de Epstein-Barr. El diagnóstico se establece por exclusión y su tratamiento se basa en el control sintomático, cicatrizantes, analgésicos y antisépticos. CASO CLÍNICO: Paciente de 15 años, con úlceras vulvares de aparición súbita acompañadas de cuadro catarral. Se indicó tratamiento local con cicatrizante, antiséptico y antiinflamatorio; al cabo de tres semanas se observó la desaparición de las lesiones y la negatividad de las pruebas que descartó el origen infeccioso. Se estableció el diagnóstico de úlcera de Lipschütz. CONCLUSIONES: La úlcera de Lipschütz es infrecuente y los niños son quienes más la padecen. Debido al carácter de desaparición espontánea y a la juventud de las pacientes, es decisivo establecer el correcto diagnóstico diferencial.

Abstract: BACKGROUND: Lipschütz Ulcers are painful, acute onset and self-limiting vulvovaginal lesions that can frequently be associated with prodromal symptoms, disappearing in 2-6 weeks without any sequelae. 70% of cases present idiopathic etiopathogenesis, and are related to Epstein-Barr virus, among others. The diagnosis is made by exclusion and its treatment is based on symptomatic control and the promotion of correct healing, using analgesics, cicatrizers and antiseptics. CASE REPORT: A 15-year-old girl reported the acute apparition of ulcerative vulvar lesions coinciding with systemic catarrhal symptoms. Local treatment with healing, antiseptic and anti-inflammatory lotions was prescribed, and after three weeks, she was reevaluated, observing the disappearance of the lesions and the negativity of the tests to rule out infectious origin, for which she was diagnosed with a Lipschütz ulcer. CONCLUSIONS: Lipschütz ulcer is rare and children are the ones who suffer most from it. Due to the spontaneous disappearance character and the youthfulness of the patients, it is decisive to establish the correct differential diagnosis.

Biological and Clinical Markers in Panic Disorder

OBJECTIVE: Classifying mental disorders on the basis of objective makers might clarify their aetiology, help in making the diagnosis, identify “at risk” individuals, determine the severity of mental illness, and predict the course of the disorder. This study aims to review biological and clinical markers of panic disorder (PD). METHODS: A computerized search was carried out in PubMed and Science Direct using the key words: “marker/biomarker/clinical marker/neurobiology/staging” combined using Boolean AND operator with “panic.” In addition, the reference lists from existing reviews and from the articles retrieved were inspected. Only English language papers published in peer-reviewed journals were included. RESULTS: Structural changes in the amygdala, hippocampus, cerebral blood level in the left occipital cortex, serotonin 5-TH and noradrenergic systems activation, aberrant respiratory regulation, hearth rate variability, blood cells and peripheral blood stem cells, hypothalamic–pituitary–adrenal axis dysregulation were identified as potential candidate biomarkers of PD. Staging was identified as clinical marker of PD. According to the staging model, PD is described as follows: prodromal phase (stage 1); acute phase (stage 2); panic attacks (stage 3); chronic phase (stage 4). CONCLUSION: The clinical utility, sensitivity, specificity, and the predictive value of biomarkers for PD is still questionable. The staging model of PD might be a valid susceptibility, diagnostic, prognostic, and predictive marker of PD. A possible longitudinal model of biological and clinical markers of PD is proposed.

Early Detection and Intervention of Autism Spectrum Disorder / 한양의대학술지

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically identified in early toddlerhood. Both retrospective and prospective follow up studies of high risk infants reveal early risk signs of ASD at 12-24 months of age. The most frequently replicated early signs of ASD are atypical visual tracking and coordination, lack of social reciprocity, abnormal social communication and unusual patterns of manipulating objects, atypical sensory exploration, expressed as uncoordinated eye contact, unresponsiveness to naming, lack of social smile, delayed development of nonverbal communication and joint attention, less sharing interest, and unusually repetitive use of objects. Early intervention, before 2 years of age, appears to change the underlying developmental trajectories of the brain in individuals with ASD. In this review, the early risk signs of ASD in infancy and toddlerhood, along with early intervention and their implications, are discussed.