FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling.

Fibroblast growth factor-2 (FGF2) is involved in the regulation of affective behaviour and shows antidepressant effects through the Akt and extracellular signal regulated kinase (ERK) 1/2 pathways. Nudix hydrolase 6 (NUDT6) protein is encoded from FGF2 gene's antisense strand and its role in the regulation of affective behaviour is unknown. Here, we overexpressed NUDT6 in the hippocampus and investigated its behavioural effects and the underlying molecular mechanisms affecting the behaviour. We showed that increasing hippocampal NUDT6 results in depression-like behaviour in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acted by inducing inflammatory signalling, specifically by increasing S100 calcium binding protein A9 (S100A9) levels, activating nuclear factor-kappa B-p65 (NF-κB-p65), and elevating microglia numbers along with a reduction in neurogenesis. Our results suggest that NUDT6 could play a role in major depression by inducing a proinflammatory state. This is the first report of an antisense protein acting through a different mechanism of action than regulation of its sense protein. The opposite effects of NUDT6 and FGF2 on depression-like behaviour may serve as a mechanism to fine-tune affective behaviour. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behaviour, as well as in neuropsychiatric disorders. KEY POINTS: Hippocampal overexpression of nudix hydrolase 6 (NUDT6), the antisense protein of fibroblast growth factor-2 (FGF2), increases depression-like behaviour in rats. Hippocampal NUDT6 overexpression triggers a neuroinflammatory cascade by increasing S100 calcium binding proteinA9 (S100A9) expression and nuclear NF-κB-p65 translocation in neurons, in addition to microglial recruitment and activation. Hippocampal NUDT6 overexpression suppresses neurogenesis. NUDT6 exerts its actions without altering the levels or downstream signalling pathways of FGF2.

Perspectives of Family Caregivers of People With Alzheimer's Disease on Caregiving Experience and Needs: A Qualitative Study.

The current study aimed to investigate the perspectives of family caregivers of people with Alzheimer's disease on caregiving experience and needs. A qualitative descriptive method was used with a sample of 23 family caregivers. Data were collected through in-depth, face-to-face interviews using a pilot-tested semi-structured interview guide. Data analysis was performed via content analysis. Three major themes emerged: (1) Stuck in Caregiving, (2) A Life in Metamorphosis, and (3) Needs. Findings revealed that caregivers struggled to manage the care process, adapt to life changes, and fulfill their needs. This study provides rich data to help create interventions to assist family caregivers. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Clean Words Come Out of Clean Minds

No abstract available.

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Management of Psychiatric Symptoms in Dementia.

Behavioral and Psychological Symptoms of Dementia (BPSD) are frequent, may start early in the disease and increase in frequency and severity over time. BPSD may be associated with medical, social, emotional, and environmental factors and potential triggers should be eliminated. Each BPSD has a unique anatomic and neurochemical profile that may help in making a diagnosis and choosing a therapy. Structured management plans help create an effective framework. Treatment options are understudied and the evidence is inconclusive for many of the pharmacological interventions. Effective nonpharmacological options should be utilized where available. Treatments should be monitored for their efficacy and safety.

Empathy as a crucial skill in disrupting disparities in global brain health.

Brain health refers to the state of a person's brain function across various domains, including cognitive, behavioral and motor functions. Healthy brains are associated with better individual health, increased creativity, and enhanced productivity. A person's brain health is intricately connected to personal, social and environmental factors. Racial, ethnic, and social disparities affect brain health and on the global scale these disparities within and between regions present a hurdle to brain health. To overcome global disparities, greater collaboration between practitioners and healthcare providers and the people they serve is essential. This requires cultural humility driven by empathy. Empathy is a core prosocial value, a cognitive-emotional skill that helps us understand ourselves and others. This position paper aims to provide an overview of the vital roles of empathy, cooperation, and interdisciplinary partnerships. By consciously integrating this understanding in practice, leaders can better position themselves to address the diverse challenges faced by communities, promote inclusivity in policies and practices, and further more equitable solutions to the problem of global brain health.

Association between polarity of first episode and solar insolation in bipolar I disorder.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

The superiority of ketofol and etomidate against propofol or thiopental anesthesia for ECT.

OBJECTIVES: Most anesthetic drugs used for electroconvulsive therapy (ECT) have dose-dependent anticonvulsive effects, counter-acting seizure induction, lowering seizure quality. However, a consummate drug for ECT anesthesia has not yet been established. Therefore, in this study, we aimed to investigate the effects of etomidate, thiopental, propofol and co-administration of ketamine-propofol (ketofol) on seizure quality and hemodynamic safety. METHODS: Registries of 121 patients (1077 sessions) were retrospectively evaluated. The effects of anesthetics on ECT-related parameters (stimulation charge, central seizure duration, number of failed stimulation trials, mean arterial pressure, and peak heart rate) were analyzed via linear mixed-effects models. RESULTS: Overall, the seizure duration decreased, and the stimulation charge increased in time with continuing sessions within a course of ECT. The decrease in seizure duration and the increase in required stimulation charge was significantly lower with etomidate and ketofol. Additionally, ketofol was significantly related to a lower number of failed stimulation trials compared to propofol. Ketofol and propofol use was associated with a significantly lower postictal mean arterial pressure. CONCLUSION: Ketofol and etomidate were equivalently superior in the rate of decrease in seizure duration and the required elevation in stimulus charge, which would interpret into valuable clinical guidance, especially for "seizure resistant" patients, and their use may potentially lower ECT related cognitive side effects.

PsiNorm: A fast, efficient and free open-source software for interpreting, reporting and archiving neuropsychological test results. / PsiNorm: Nöropsikolojik Test Verilerinin Degerlendirilmesi, Rapor Hazirlanmasi ve Arsivlenmesi için Hizli ve Etkin Bir Açik Yazilim.

OBJECTIVE: In many clinics, calculation and interpretation of neuropsychological test results, along with reporting, data organization and archiving of the data are done manually. In this era where most of the similar processes are automated, manual application may result in excessive time consumption, unnecessary use of qualified work-force, and is also open to error. A software that automates these processes for neuropsychological tests used for dementia assessment may overcome these issues. METHOD: We aimed to develop a free, open source software not requiring specialized training, which would optimise the calculation, preparation of personal reports and archiving processes of neuropsychological tests, hence would easily be incorporated in to the daily work of psychologists. We've used Python 3.6 as the programming language, and JSON was used as the data interchange format to allow for personal alterations in the content. The tests were selected among those which are in common use for neuropsychological evaluation of adults in Turkey, with available norm values. (Funding: TUBITAK 214S048). RESULTS: PsiNorm was developed, comprising widely used standardized tests for cognitive evaluation of adults in Turkey. The software is lightweight, compatible with most common operating systems, and easy-to-use. We've shown that Psinorm significantly reduced the time required for calculation of percentiles and norms as well as for producing a draft report. The reports are prepared in .txt format and the databases are prepared in MS Excel ve CSV formats. PsiNorm is available freely at psinorm.org. CONCLUSION: PsiNorm is a free, open-source software which is available for researchers and clinicians who perform neuropsychological tests. PsiNorm provides significant time and labor-force benefits, is easy-touse and can be customized by the user.

Spectral Analysis of Lithium Tremor.

INTRODUCTION: Lithium has proven efficacy in bipolar affective disorder (BAD) but induces tremor as a side effect in a quarter of patients. Lithium tremor (LT) shares some clinical characteristics of essential tremor (ET) and Parkinson's disease tremor (PT), which might cause difficulties in differential diagnosis. Furthermore, current knowledge of LT is lacking detailed electrophysiological characterization. Here, we present detailed spectral attributes of accelerometric tremor recordings as a diagnostic tool for LT. METHODS: 10 patients (7 males, 3 females) between ages of 29-68, who were on lithium for BAD for 2-12 years, were evaluated for hand tremor with the spectral analysis of accelerometric recordings with different postures. Tremor severity was rated clinically on WHIGET (Washington Heights-Inwood Genetic Study of Essential Tremor) scale. Results were analyzed in comparison to results of ET (n=19) and PT (n=19) patients from our database. RESULTS: LT was most prominent at extensor postures with an average peak frequency (PF) of 8.0±0.3 Hz and an extremely low amplitude, high harmonic components and high noise level. The average PF of LT was similar to that of ET (7.3±0.4 Hz), but higher than that of PT (5.3±0.2 Hz) (p<0.0001). With weight loading, the PF of LT showed an increase of 1.3 Hz. Average amplitude of PT was higher than that of both LT and ET (p<0.0001); harmonic components of LT was comparable to PT whereas noise levels were similar to that of ET. Mean WHIGET score of LT (6.5±0.5) was significantly lower than that of ET (13.1±1) (p<0.0001). CONCLUSION: Electrophysiological features detected by accelerometry may help in differential diagnosis of LT from ET and PT.

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder.

BACKGROUND: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. METHODS: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). RESULTS: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. CONCLUSION: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.

Clinical findings and mutational spectrum of neurofibromatosis type 1 patients in a single center of south part of Turkey.

AIM: The aim of this study is to determine the mutation spectrums and clinical characteristics of NF1 patients followed up in our center and to investigate whether there is a genotype-phenotype relationship. MATERIAL AND METHODS: Sixty-three children and 34 relatives diagnosed with NF1 were included in the study. Age, gender, family history, clinical features, tumors detected in the patient at the time of diagnosis or during follow-up, orbital and cerebral magnetic resonance imaging (MRI) findings were recorded. Also results of the NF1 gene analysis results were recorded. RESULTS: Fifty-three different mutations were found as a result of the NF1 gene analysis studied from patients and their family members. Among these 53 mutations, stop codon mutation was the most frequently detected mutations. Sixteen out of 50 (32%) mutations were found to be novel mutations. Twenty-eight tumors developed in our patients. Twenty of them were optic gliomas and others were medullary thyroid carcinoma, glioblastome multiforme, pons glioma, acute lymphoblastic leukemia, pilocytic astrositoma, hypothalamic glioma, cerebral hamartoma and cardiac fibroma. No genotype-phenotype relationship was detected in patients Conclusion: Comprehensive mutation analysis of NF1 will increase our knowledge due to its different phenotypic characteristics even in the same mutation.

Weight Loss Associated with Clozapine: A Case Report. / Klozapin Kullanimina Bagli Kilo Kaybi: Vaka Sunumu.

Clozapine is one of the second generation antipsychotics most commonly associated with serious metabolic side effects including weight gain. Unexpectedly, weight loss can also be seen as a rare side effect of clozapine. The mechanism underlying clozapine induced weight loss is not clearly understood. Several factors including certain brain areas, neurotransmitters, neuropeptides and genetic variants were identified to play a role in weight loss associated with clozapine. In some patients who were reported to have a significant weight loss (13.5-50% of body weight) with clozapine, weight loss might not be associated with any underlying physical disorder. Weight loss may be due to the patients' engagement in diet and exercise after clinical improvement, pharmacodynamic effects of clozapine, or other medical problems such as gastrointestinal tract hypomotility caused by clozapine. Some case reports suggested that clozapine-associated weight loss might be a sign of poor response to clozapine. Clinicians should keep in mind the fact that a specific group of patients may lose weight during clozapine treatment. In this case report, possible causes of weight loss due to clozapine use is discussed. We also discussed the possible relationship between clozapine dose and weight loss which has not drawn attention in previous case reports.

Effective High-dose Interferon-α Therapy in a 13-Year-Old Girl With Erdheim-Chester Disease.

Erdheim-Chester disease (ECD) is a proliferative disorder of non-Langerhans histiocytes with a higher incidence in the fifth to seventh decades and rarer occurrence in the pediatric population. Although ECD typically involves bone, it can also affect the central nervous system, cardiovascular system, retro-orbital space, retroperitoneal space, and kidneys, lungs, and skin. A 13-year-old Syrian girl who presented with multisystemic involvement was diagnosed with ECD. The B-Raf proto-oncogene V600E mutation was not detected in ECD lesions. Response to the high-dose interferon-α therapy was excellent in this pediatric patient. In this article, pediatric ECD case reports are also reviewed.

A Systematic Review of Neuropsychological Tests for the Assessment of Dementia in Non-Western, Low-Educated or Illiterate Populations.

OBJECTIVE: Neuropsychological tests are important instruments to determine a cognitive profile, giving insight into the etiology of dementia; however, these tests cannot readily be used in culturally diverse, low-educated populations, due to their dependence upon (Western) culture, education, and literacy. In this review we aim to give an overview of studies investigating domain-specific cognitive tests used to assess dementia in non-Western, low-educated populations. The second aim was to examine the quality of these studies and of the adaptations for culturally, linguistically, and educationally diverse populations. METHOD: A systematic review was performed using six databases, without restrictions on the year or language of publication. RESULTS: Forty-four studies were included, stemming mainly from Brazil, Hong Kong, Korea, and considering Hispanics/Latinos residing in the USA. Most studies focused on Alzheimer's disease (n = 17) or unspecified dementia (n = 16). Memory (n = 18) was studied most often, using 14 different tests. The traditional Western tests in the domains of attention (n = 8) and construction (n = 15), were unsuitable for low-educated patients. There was little variety in instruments measuring executive functioning (two tests, n = 13), and language (n = 12, of which 10 were naming tests). Many studies did not report a thorough adaptation procedure (n = 39) or blinding procedures (n = 29). CONCLUSIONS: Various formats of memory tests seem suitable for low-educated, non-Western populations. Promising tasks in other cognitive domains are the Stick Design Test, Five Digit Test, and verbal fluency test. Further research is needed regarding cross-cultural instruments measuring executive functioning and language in low-educated people.

[Relationship Between Alcohol Dependence and Neuropeptide Y (NPY) Gene Promoter Polymorphisms in A Turkish Sample]. / Türkiye Örnekleminde Nöropeptit Y Geni (NPY) Promotor Polimorfizmleri ve Alkol Bagimliligi Arasindaki Iliski.

OBJECTIVE: Neuropeptide Y (NPY) is a protein widely expressed in the central nervous system and involved in diverse physiological processes, such as emotional regulation, nutritional behavior, and stress. In some populations, studies on alcohol dependence (AD) and the NPY gene have found that NPY variations increase alcohol consumption and thus may potentially be associated with AD. In this study, we investigated the relationship between NPY gene promoter polymorphisms and phenotypes related to alcohol use. METHOD: A total of 417 male participants comprising 252 individuals with AD and 165 healthy individuals were included in this study and phenotypic data were collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and DNA sequencing METHODS were used for genotyping the rs16147 and rs17149106 polymorphisms in the promoter region of the NPY gene. The data of 384 participants were analysed to evaluate the possible relationship between genotypes and the diagnosis of AD, family history of AD, the severity of AD using the Michigan Alcoholism Screening Test (MAST), the age of onset of problematic alcohol use, the average amount of alcohol consumed per day for the last six months and the lifetime maximum alcohol consumption in one day. RESULTS: A significant difference was found between the AD and control groups concerning rs16147 polymorphism genotype distribution (p=0.025). No association with polymorphisms and alcohol-related phenotypes were demonstrated in the AD group. CONCLUSION: To our knowledge, this study shows for the first time in the literature that alcohol dependence is associated with NPY rs16147 polymorphism in the Turkish population.

[Effects of Nitric Oxide Synthase-1 Exon 1f-VNTR Gene Polymorphism on the Clinical Symptoms of Alcohol Dependence,Impulsivity and Comorbid Attention Deficit Hyperactivity Disorder]. / Alkol Bagimlilarinda Nitrik Oksit Sentaz-1 Ekzon 1f-VNTR Gen Polimorfizmi’nin Bagimlilik ile Iliskili Klinik Özellikler, Dürtüsellik ve Eslik Eden Dikkat Eksikligi Hiperaktivite Belirtileri Üzerine Etkisi.

OBJECTIVE: We planned to compare individuals with alcohol dependence (AD) and healthy controls on the frequency of NOS1 exon 1f-VNTR gene polymorphism and to investigate the effects of this polymorphism on the clinical symptoms of alcohol dependence, impulsiveness and comorbid attention deficit hyperactivity disorder (ADHD) symptoms. METHOD: A total of 282 participants consisting of 153 patients and 129 age and gender matched healthy individuals were inluded in the study. All participants were evaluated with Structured Clinical Interview for DSM-IV Axis 1 disorders (SCID-I) and Michigan Alcohol Screening Test (MAST), Barratt Impulsiveness Scale (BIS-11), UPPS Impulsive Behavior Scale, Adult Attention Deficit and Hyperactivity Diagnosis Scale (ADHDS), Family History Research Diagnostic Criteria (FHDRC). The QF-PCR fragment protocols were used for genetic analyses. Allele fragments of ≤176 bp and >176 bp sizes were separated and 3 different genotypes were determined as the SS, SL and LL. Associations of these genotypes with symptoms of AD severity, impulsiveness and comorbid ADHD were investigated. RESULTS: The AD and control groups did not differ significantly on the basis of NOS1 exon 1f-VNTR gene polymorphism. Also, significant correlations between this polymorphism and symptoms of AD severity, impulsiveness and ADHD were not determined. CONCLUSION: Results of our study do not indicatea significant association between the NOS1 exon 1f-VNTR genotypes and AD, subgroups of AD, impulsiveness or comorbid ADHD semptoms.