Neuropsychiatric Features Research Articles

Neuropsychiatric and cognitive features of major depressive disorder in aging, based on the data from the US National Alzheimer's Coordinating Center (NACC)

ObjectiveThe diagnosis of Major Depressive Disorder (MDD) is based on the DSM-V criteria and is established by a clinician. This allows quantifying depression based on clinical criteria. As such, MDD differs from other types of depressions that are measured by subjective scales. Here, we evaluated the MDD risk factor on other neuropsychiatric symptoms (NPS) as well as MDD association with cognitive performance in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and Healthy Controls (HC). MethodsData of 208 patients with AD, 291 patients with MCI and 647 HC were extracted from the National Alzheimer's Coordinating Center database. All participants included in this study were assessed by a physician for the MDD criteria, underwent an NPS evaluation using the NeuroPsychiatric Inventory, and a comprehensive cognitive assessment. Participants were classified as being with and without MDD. We performed logistic regression and MANCOVA models respectively with NPS and cognitive performance as variables of interest and MDD as fixed factors within each group. The MANCOVA was controlled for the effects of age, sex, and education. ResultsMDD increased the risk for psychotic, affective and behavioral NPS in MCI, as well as affective and behavioral NPS in HC and AD. Also, MCI with MDD had lower performance on selective attention and mental flexibility. ConclusionsMDD seems to increase the probability of a prevalence of NPS in all groups (HC, MCI and AD). Longitudinal data processing would help to understand the neuropsychiatric evolution of elderly subjects with MDD.

Human tau-overexpressing mice recapitulate brainstem involvement and neuropsychiatric features of early Alzheimer’s disease

Alzheimer’s disease (AD) poses an ever-increasing public health concern as the population ages, affecting more than 6 million Americans. AD patients present with mood and sleep changes in the prodromal stages that may be partly driven by loss of monoaminergic neurons in the brainstem, but a causal relationship has not been firmly established. This is due in part to a dearth of animal models that recapitulate early AD neuropathology and symptoms. The goal of the present study was to evaluate depressive and anxiety-like behaviors in a mouse model of AD that overexpresses human wild-type tau (htau) prior to the onset of cognitive impairments and assess these behavior changes in relationship to tau pathology, neuroinflammation, and monoaminergic dysregulation in the dorsal raphe nucleus (DRN) and locus coeruleus (LC). We observed depressive-like behaviors at 4 months in both sexes and hyperlocomotion in male htau mice. Deficits in social interaction persisted at 6 months and were accompanied by an increase in anxiety-like behavior in males. The behavioral changes at 4 months coincided with a lower density of serotonergic (5-HT) neurons, downregulation of 5-HT markers, reduced excitability of 5-HT neurons, and hyperphosphorylated tau in the DRN. Inflammatory markers were also upregulated in the DRN along with protein kinases and transglutaminase 2, which may promote tau phosphorylation and aggregation. Loss of 5-HT innervation to the entorhinal cortex and dentate gyrus of the hippocampus was also observed and may have contributed to depressive-like behaviors. There was also reduced expression of noradrenergic markers in the LC along with elevated phospho-tau expression, but this did not translate to a functional change in neuronal excitability. In total, these results suggest that tau pathology in brainstem monoaminergic nuclei and the resulting loss of serotonergic and/or noradrenergic drive may underpin depressive- and anxiety-like behaviors in the early stages of AD.

Where Do Neurodevelopmental Disorders Go? Casting the Eye Away from Childhood towards Adulthood

Neurodevelopmental disorders (NDDs) encompass a group of complex conditions with onset during the early developmental period. Such disorders are frequently associated with a number of neuropsychiatric features, the most prevalent ones being autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, communication and specific learning disorders, and motor disorders. These conditions are characterized by wide genetic and clinical variability, and although they were previously conceptualized as childhood-limited disorders, NDDs are progressively being recognized as persistent conditions with a potentially relevant impact on the quality of life and overall functioning during adult life. In addition, emerging evidence seems to point towards the hypothesis of a neurodevelopmental continuum, according to which NNDs could portray different time-dependent outcomes, depending on the severity of the altered brain development. Despite representing lifelong phenotypes, they are often not promptly identified and/or managed in adulthood. In this regard, specific guidelines on clinical and therapeutic approaches for these conditions have not yet been delineated. In this view, future research investigations should be encouraged to broaden available knowledge, characterize the clinical course of NDDs across an individual's lifespan, and better understand the patterns of aging-related concerns in adults with an NDD diagnosis. Additionally, considering the difficulties many young adults encounter while transitioning from childhood to adult mental health services, new, specific programs should be developed and existing programs should be implemented to improve the transition process and for the management of NDDs in adulthood.

Septin-3 autoimmunity in patients with paraneoplastic cerebellar ataxia

BackgroundSeptins are cytoskeletal proteins with filament forming capabilities, which have multiple roles during cell division, cellular polarization, morphogenesis, and membrane trafficking. Autoantibodies against septin-5 are associated with non-paraneoplastic cerebellar ataxia, and autoantibodies against septin-7 with encephalopathy with prominent neuropsychiatric features. Here, we report on newly identified autoantibodies against septin-3 in patients with paraneoplastic cerebellar ataxia. We also propose a strategy for anti-septin autoantibody determination.MethodsSera from three patients producing similar immunofluorescence staining patterns on cerebellar and hippocampal sections were subjected to immunoprecipitation followed by mass spectrometry. The identified candidate antigens, all of which were septins, were expressed recombinantly in HEK293 cells either individually, as complexes, or combinations missing individual septins, for use in recombinant cell-based indirect immunofluorescence assays (RC-IIFA). Specificity for septin-3 was further confirmed by tissue IIFA neutralization experiments. Finally, tumor tissue sections were analyzed immunohistochemically for septin-3 expression.ResultsImmunoprecipitation with rat cerebellum lysate revealed septin-3, -5, -6, -7, and -11 as candidate target antigens. Sera of all three patients reacted with recombinant cells co-expressing septin-3/5/6/7/11, while none of 149 healthy control sera was similarly reactive. In RC-IIFAs the patient sera recognized only cells expressing septin-3, individually and in complexes. Incubation of patient sera with five different septin combinations, each missing one of the five septins, confirmed the autoantibodies’ specificity for septin-3. The tissue IIFA reactivity of patient serum was abolished by pre-incubation with HEK293 cell lysates overexpressing the septin-3/5/6/7/11 complex or septin-3 alone, but not with HEK293 cell lysates overexpressing septin-5 as control. All three patients had cancers (2 × melanoma, 1 × small cell lung cancer), presented with progressive cerebellar syndromes, and responded poorly to immunotherapy. Expression of septin-3 was demonstrated in resected tumor tissue available from one patient.ConclusionsSeptin-3 is a novel autoantibody target in patients with paraneoplastic cerebellar syndromes. Based on our findings, RC-IIFA with HEK293 cells expressing the septin-3/5/6/7/11 complex may serve as a screening tool to investigate anti-septin autoantibodies in serological samples with a characteristic staining pattern on neuronal tissue sections. Autoantibodies against individual septins can then be confirmed by RC-IIFA expressing single septins.

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.

Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A. EA3-8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists. A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized. EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorders (PDHA1, PDHX, ACO2), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause. EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.

The influence of culture and cognitive reserve on the clinical presentation of behavioural-variant frontotemporal dementia

Characterisation of the clinical profile of behavioural-variant frontotemporal dementia (bvFTD) has predominantly been based on Western samples. Some small studies have suggested that the clinical profile may differ in culturally and linguistically diverse populations. Additionally, there is evidence that patients from non-English speaking backgrounds may have more cognitive reserve, allowing them to tolerate more disease pathology before clinical symptoms emerge. This study aims to characterise the clinical profiles of patients with bvFTD from culturally diverse backgrounds. BvFTD patients were classified as Australian-born (Australian) or Culturally and Linguistically Diverse-English-speaking (CALD-English) and Culturally and Linguistically Diverse-Language Other Than English (CALD-LOTE). Clinical features, cognitive test performance and cognitive reserve were compared between groups. Voxel-based morphometry was used to examine the neural correlates of cognitive reserve. 107 patients with bvFTD (53 Australian, 36 CALD-English, 18 CALD-LOTE) and 51 controls were included. Analysis of neuropsychiatric features revealed more elation in Australian patients compared to CALD-English patients, with trends for CALD-LOTE patients to report more irritability. CALD-LOTE patients also had higher cognitive reserve and showed relatively greater verbal than non-verbal cognitive impairment. Neuroimaging analyses revealed that higher cognitive reserve was associated with lower integrity in the frontal–temporal regions associated with typical disease pathology in bvFTD. Our findings support the hypothesis that cognitive reserve may delay early cognitive decline in culturally and linguistically diverse patients, although these patients may still show poor verbal performance due to cultural testing biases. Clinically, these results highlight the need to consider cultural and linguistic background to inform the assessment of dementia.

A Large Turkish Cohort of Williams Syndrome: The Evaluation of Facial, Cardiovascular, and Neuropsychiatric Features.

Williams syndrome is caused by a microdeletion at 7q11.23 and is characterized by a distinctive face, cardiovascular disease, and intellectual disability with a specific cognitive and behavioral profile. This study aims to evaluate the clinical features and obtain important information that can guide early diagnoses and correct follow-up. The study included 78 patients whose diagnoses were confirmed by fluorescent in situ hybridization. Facial features, anthropometric measurements, and neurocognitive, endocrine, and urinary system evaluations were obtained from the medical records, and photographs of the patients were evaluated retrospectively. The most common complaints at admission were cardiovascular disease and atypical face. The mean age at admission was 39 ± 4.8 months. The mean age of patients presenting with atypical face was 41 ± 5.6 months, while it was 11 ± 3.1 months in patients presenting with cardiovascular disease. Short nose/bulbous nasal type with anteverted nares and periorbital fullness, which are diagnostic facial features, were present in all patients in the infantile/ early childhood period. 80% of the patients had cardiovascular disease; supravalvular aortic stenosis (53.8%) and peripheral pulmonary artery stenosis (41%) were the most common cardiac anomalies.Intel lectu al/de velop menta l disability was present in 75.6% of the patients. Behavioral disorders including autism spectrum disorder and attention deficit hyperactivity disorder were detected in 50% of our patients. Hypersensitivity to loud and/or sudden sounds was present in all patients. We highlighted that recognition of facial findings is important for early diagnosis, especially in patients without cardiovascular disease. The frequency of cardiovascular, endocrinological, renal anomalies, and intellectual disab ility /deve lopme ntal delay was described that provide valuable information in the follow-up of patients.

Experimental Models of Gulf War Illness, a Chronic Neuropsychiatric Disorder in Veterans.

Gulf War illness (GWI) is a chronic multifaceted condition with debilitating pain and fatigue, as well as sleep, behavioral, and cognitive impairments in war veterans. Currently, there is no effective treatment or cure for GWI; therefore, there is a critical need to develop experimental models to help better understand its mechanisms and interventions related to GWI-associated neuropsychiatric disorders. Chemical neurotoxicity appears to be one cause of GWI, and its symptoms manifest as disruptions in neuronal function. However, the mechanisms underlying such incapacitating neurologic and psychiatric symptoms are poorly understood. The etiology of GWI is complex, and many factors including chemical exposure, psychological trauma, and environmental stressors have been associated with its development. Attempts have been made to create GWI-like symptomatic models, including through chronic induction in mice and rats. Here, we present a brief protocol of GWI in rats and mice, which exhibit robust neuropsychiatric signs and neuropathologic changes reminiscent of GWI. This article provides a guide to working protocols, application of therapeutic drugs, outcomes, troubleshooting, and data analysis. Our broad profiling of GWI-like symptoms in rodents reveals features of progressive morphologic and long-lasting neuropsychiatric features. Together, the GWI model in rodents shows striking consistency in recapitulating major hallmark features of GWI in veterans. These models help identify mechanisms and interventions for GWI. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Experimental induction of Gulf War illness in rats Support Protocol 1: Monitoring of Gulf War illness signs and neuroimaging analysis in rats Basic Protocol 2: Experimental induction of Gulf War illness in mice Support Protocol 2: Monitoring of Gulf War illness signs and neuropathology analysis in mice.

Neuropsychiatric presentations of hypocortisolaemia - a literature review

IntroductionPatient populations in psychiatry can have low cortisol for many reasons such as adrenalitis, secondary adrenal insufficiency and poor compliance with glucocorticoid replacement therapies. A literature review in 2005 highlighted the prevalence of neuropsychiatric features in those with low cortisol. Unfortunately, this has received little to no attention in the wider literature and hypocortisolaemia is often overlooked as a cause of neuropsychiatric presentations in clinical practice.ObjectivesReview the literature to understand what psychiatric features hypocortisolaemic patients present with and any themes between cases.MethodsA literature review on neuropsychiatric presentations of hypocortisolaemia was performed using PUBMED and Google Scholar. English language studies from 2005 to October 2022 were included and searched for using the following term: (Hypocortisolaemia* OR “Low-cortisol” OR Addisons OR Adrenal-crisis OR “Adrenal insufficiency”) AND (Psychiatric OR Hallucination OR Neuropsychiatric OR “Neuropsychiatric symptoms” OR Pyschosis*). Citations in relevant papers were also reviewed.Results7 case reports were identified, 5 male (71%) and 2 female (29%) with an average age of 42 (28-63). The cause was identified as Addisons’ disease in 4 patients (57%) and secondary adrenal insufficiency in 3 patients (43%). Hallucination or delusion was the most prevalent symptom with 86% of patients initially presenting with it, followed by depression (43%) and speech abnormality (14%). In all cases, basic blood sets (Full blood count, urea & electrolytes and liver function tests) were done in an initial assessment. 6 patients presented with hyponatraemia, and 4 of these patients had hyponatraemia as their only abnormality within their U&E profile. In one patient this delayed their diagnosis by several years. One patient developed psychosis again when being treated with glucocorticoid therapy. In 4 patients, adrenal pathology was not suspected and cortisol was not tested until initial differentials were investigated and ruled out.ConclusionsFurther case reports highlight psychosis being a key feature of hypocortisolaemia that presents initially with neuropsychiatric symptoms. Cortisol levels should be considered in initial investigations of psychosis if hyponatraemia is discovered even in the absence of hyperkalaemia to help aid an earlier diagnosis. A rebound psychosis may be seen once starting glucocorticoid therapy. Additionally, there should be consideration of neuropsychiatric monitoring in stable psychiatric patients undergoing cortisol treatment.Disclosure of InterestNone Declared

Neurological, Psychiatric, and Multisystemic Involvement of Fragile X Syndrome Along With Its Pathophysiology, Methods of Screening, and Current Treatment Modalities.

Fragile X syndrome (FXS) is a hereditary disease that predominantly leads to intellectual disability (ID) in boys. It is the second prominent cause of ID, which manifests as a result of the atypical development of the cytosine-guanine-guanine (CGG) region. This irregular extension of the CGG region gives rise to methylation and silencing of the fragile X mental retardation 1 (FMR1) gene, causing a loss of the fragile X mental retardation 1 protein (FMRP). This reduction or loss of FMRP is the main cause of ID. It has a multisystemic involvement showing neuropsychiatric features such as ID, speech and language delay, autism spectrum disorder, sensory hyperarousal, social anxiety, abnormal eye contact, shyness, and aggressive behaviour. It is also known to cause musculoskeletal symptoms, ocular symptoms, cardiac abnormalities, and gastrointestinal symptoms. The management is challenging, and there is no known cure for the disease; hence an early diagnosis of the condition is needed through prenatal screening offered to couples with familial history of ID before conception. The management rests on non-pharmacological modalities, including applied behaviour analysis, physical therapy, occupational therapy, speech-language therapy, and pharmacologic management through symptomatic treatment of comorbid behaviours and psychiatric problems and some forms of targeted therapy.

Anti-NMDA Receptor Encephalitis presenting with severe episodic hypertension: a case report

Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis is one of the most commonly emerging autoimmune encephalitis in children and young adults in recent years. Clinical manifestations range from prodromal symptoms to seizures, movement disorder, psychiatric manifestations, cognitive/speech impairment, and autonomic dysfunction. Our case presented with initial symptoms of severe episodic hypertension, sweating, agitation, and tachycardia. She received early care for pheochromocytoma and panic disorder in Qatar, but there was no relief. Three weeks later, she presented in our emergency room with seizures, cognitive/speech impairment, and orofacial dyskinesia. Electroencephalography EEG revealed right hemispheric delta activity and cerebrospinal fluid CSF anti-NMDA Receptor IgG was positive. Magnetic resonance imaging MRI brain and CSF studies were normal. She was treated symptomatically for hypertension and psychiatric manifestations. She received high dosage pulse intravenous methylprednisolone, followed by intravenous immunoglobulin, which significantly alleviated her cognitive, neuropsychiatric, and autonomic features. Severe Hypertension is an uncommon presentation of Anti- NMDAR encephalitis. Early recognition and prompt management improves prognosis and long term sequelae.

Neuropsychiatric feature-based subgrouping reveals neural sensory processing spectrum in female FMR1 premutation carriers: A pilot study.

Fragile X Syndrome (FXS) is rare genetic condition characterized by a repeat expansion (CGG) in the Fragile X messenger ribonucleoprotein 1 (FMR1) gene where individuals with greater than 200 repeats are defined as full mutation. FXS clinical presentation often includes intellectual disability, and autism-like symptoms, including anxiety and sensory hypersensitivities. Individuals with 55 to <200 CGG repeats are said to have the FMR1 premutation, which is not associated with primary characteristics of the full mutation, but with an increased risk for anxiety, depression, and other affective conditions, as well as and impaired cognitive processing differences that vary in severity. Defining subgroups of premutation carriers based on distinct biological features may identify subgroups with varying levels of psychiatric, cognitive, and behavioral alterations. The current pilot study utilized 3 cluster subgroupings defined by previous k means cluster analysis on neuropsychiatric, cognitive, and resting EEG variables in order to examine basic sensory auditory chirp task-based EEG parameters from 33 females with the FMR1 premutation (ages 17-78). Based on the predefined, neuropsychiatric three-cluster solution, premutation carriers with increased neuropsychiatric features and higher CGG repeat counts (cluster 1) showed decreased stimulus onset response, similar to previous ERP findings across a number of psychiatric disorders but opposite to findings in individuals with full mutation FXS. Premutation carriers with increased executive dysfunction and resting gamma power (cluster 2) exhibited decreased gamma phase locking to a chirp stimulus, similar to individuals with full mutation FXS. Cluster 3 members, who were relatively unaffected by psychiatric or cognitive symptoms, showed the most normative task-based EEG metrics. Our findings suggest a spectrum of sensory processing characteristics present in subgroups of premutation carriers that have been previously understudied due to lack of overall group differences. Our findings also further validate the pre-defined clinical subgroups by supporting links between disturbances in well-defined neural pathways and behavioral alterations that may be informative for identifying the mechanisms supporting specific risk factors and divergent therapeutic needs in individuals with the FMR1 premutation.

Aneurysmal subarachnoid hemorrhage with PFBC and beta thalassemia: a case report

BackgroundPrimary familial brain calcification (PFBC), habitually called Fahr’s disease, is characterized by bilateral calcification of the basal ganglia, accompanied by extensive calcification of the cerebellar dentate nucleus, brainstem cerebrum, and cerebellum at the grey-white matter junction. However, there are few reports about PFBC with aneurysmal subarachnoid hemorrhage (aSAH) and thalassemia.Case presentationWe describe a patient admitted to the hospital with an acute deterioration in the level of consciousness with no history of neuropsychiatric features or movement disorders. After computed tomography (CT) and CT angiography (CTA), the patient was diagnosed with PFBC, accompanied by aneurysmal subarachnoid haemorrhage (aSAH), intracranial haemorrhage (ICH), and hemoglobin electrophoresis suggested beta-thalassemia. This patient underwent craniotomy aneurysm clipping and intracranial hematoma removal.ConclusionsFor patients with PFBC, we should pay attention to their blood pressure and intracranial vascular conditions. The CTA is necessary to clarify the cerebrovascular conditions of the patient, especially when combined with hypertension and persistent headache or other related prodromal symptoms of cerebrovascular disease.

Sleep and Sleep Complaints in Juvenile Fibromyalgia Syndrome.

To investigate sleep quality in juvenile fibromyalgia syndrome (JFS) and its effect on the global burden of the disease. Consecutive patients with JFS who performed full-night polysomnography (PSG) were included in this cross-sectional study. JFS-related symptoms, neuropsychiatric features, and sleep quality were assessed using self-report measures. PSG sleep parameters, including N3 distribution index, were obtained from patients and age-matched healthy controls. We included 25 patients (20 females, median age 15.7 yrs). Nonrestorative sleep was reported by 22 of 25 (88%) patients. Patients with JFS showed significantly longer sleep period time (P = 0.004) and increased wake after sleep onset (P = 0.03) compared to healthy peers. The N3 distribution index was significantly lower in patients than in the control group (P = 0.02). Subjective poor sleep quality was related to Widespread Pain Index (WPI; r s -0.65), Symptom Severity Scale (r s -0.64), depressive symptoms (r s -0.58), fatigue (r s -0.44), and symptom severity upon awakening (r s -0.65). The N3 distribution index was correlated to depressive symptoms (r s 0.41) and irritability (rs 0.40). On multiple regression analysis, WPI was predicted by subjective sleep quality (β -0.32, P = 0.04), whereas depressive symptoms were predicted by subjective sleep measures (β -0.32, P = 0.04) and PSG parameters (N3 min: β -0.07, P = 0.03). Sleep complaints are a key hallmark of JFS and have significant effect on relevant clinical domains of the disease, such as pain and depression.

Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales

BackgroundCurrent clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage.Methods832 participants from the Genetic FTD Initiative (GENFI) were recruited:...

Neuropsychological and Neuropsychiatric Features of Chronic Migraine Patients during the Interictal Phase.

This study aimed to examine the presence of neuropsychological deficits and their relationships with clinical, pharmacological, and neuropsychiatric characteristics in chronic migraine (CM) patients assessed during a headache-free period. We enrolled 39 CM patients (mean age: 45.4 years; male/female ratio: 3/36) and 20 age-, sex-, and education-matched healthy controls (HCs, mean age: 45.5 years; male/female ratio: 2/18) in a case-control study. All CM patients underwent a full and extensive clinical, neuropsychiatric, and neuropsychological evaluation to evaluate cognitive domains, including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory (WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. Although more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI), with the most frequent impairments occurring in short- and long-term verbal episodic memory and inhibitory control (in approximately 90% of these patients), almost half of the patients (46%) showed no NI. Moreover, the severity of NI was positively associated with the number of pharmacological treatments received. Remarkably, disease-related symptom severity and headache-related disability explained global neuropsychological performance in CM patients. The presence of cognitive and neuropsychiatric dysfunction during the interictal phase occurred in more than half of CM patients, increasing migraine-related disability and possibly exerting a negative impact on health-related quality of life and treatment adherence.

Diencephalic versus Hippocampal Amnesia in Alzheimer's Disease: The Possible Confabulation-Misidentification Phenotype.

Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants. We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype. We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test. Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (p < 0.001), temporal disorientation (p < 0.02), misidentification (p = 0.013), other delusions (p = 0.002), and logorrhea (p = 0.004) than the CA-ADs. In addition, more social disinhibition (p = 0.018), reduction of insight (p = 0.029), and hallucination (p = 0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy. We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.

Huntington's Disease in Chile: Epidemiological and Genetic Aspects.

Huntington's disease (HD) is a neurodegenerative, autosomal dominant disabling condition due to an expansion of the CAG trinucleotide in the HTT gene. Motor, psychiatric, and cognitive disorders characterize it. Chilean reports on HD in the era of molecular diagnosis were wanted. This is a retrospective analysis of a prospective cohort of patients with HD seen at the Center for Movement Disorders (CETRAM) in Chile between 2013 and 2019. Sociodemographic, genotype, and neuropsychiatric features were investigated. One hundred three probands with HD were identified. The majority (63.1%) were born in the metropolitan region, followed by the VIII and V regions with 8.73% and 7.76%, respectively. When pedigrees were analyzed, ninety unrelated families encompassing 1,007 individuals were identified; among relatives, other 35 manifested HD, and 106 died of HD. Besides, five hundred seventy-nine individuals were at genetic risk. The minimum estimated prevalence of HD in Chile in 2019 was 0.72 × 100,000 inhabitants. The mean CAG repeats (CAGR) of 47.2 ± 10.74 for the expanded allele and 17.93 ± 2.05 for the normal allele. The mean age of onset was 41.39 ± 13.47 years. Juvenile cases represented 7.8% of this cohort, and 4.9% had a late onset. There was a negative correlation between the age of onset and the CAGR of the expanded allele (r =-0.84 p &lt; 0.0001). Besides, 79.6% had a family history of HD. This is the first report characterizing genetics, motor, and neuropsychiatric features in patients with HD in Chile. The mean length of CAGR expansion of the abnormal allele was similar to previous reports in North America (i.e., Mexico and Canada) and higher than that reported in the neighboring country of Argentina. According to previous estimations, the minimal prevalence of HD in Chile may be lower than expected.

The COVID-19 pandemic: new challenges for the mental health protection system.

The comparative investigation of the scientific research materials and systematization of the latest data on the epidemiological state, pathogenetic mechanisms, clinical manifestations, risk factors, and psychopathological consequences of the impact of the COVID-19 pandemic on the mental health of the population is needed for the further targeted development of treatment and rehabilitation measures. The COVID-19 pandemic has been increasingly viewed through the lens of serious global mental health issues. This article analyzes the results of original research and publications data on the etiopathogenesis, neuropsychiatric features, and risk factors of mental disorders associated with the pandemic. The study was carried out within the scope of the scientific research work of the Department of General, Children's Forensic Psychiatry, and Narcology of the Shupyk National Healthcare University of Ukraine. Its title was "Development of a multimodal system of restorative therapy and medical and psychological rehabilitation of patients with COVID-19, based on the study of leading pathogenetic mechanisms" (state registration number 0121U114707). Despite the recent rapid increase in the number of sources in the literature devoted to the consequences of the COVID-19 pandemic, several questions remain unresolved. This especially applies to disorders in the mental sphere, concerning clinical phenomenology, features of emotional and cognitive disturbances, personal response, levels of social functioning and the quality of life of patients who have suffered from COVID-19. The data obtained can serve as the basis for the further development of a multimodal model of hierarchical structural-functional pathogenetic links of mental disorders, as well as a target-oriented system of restorative therapy and medical-psychological rehabilitation of patients who have suffered from COVID-19.

Transcriptome Profile in the Mouse Brain of Hepatic Encephalopathy and Alzheimer's Disease.

Hepatic encephalopathy (HE) is a chronic metabolic disease accompanied by neuropathological and neuropsychiatric features, including memory deficits, psychomotor dysfunction, depression, and anxiety. Alzheimer's disease (AD), the most common neurodegenerative disease, is characterized by tau hyperphosphorylation, excessive amyloid beta (Aβ) accumulation, the formation of fibrillary tangles, hippocampus atrophy, and neuroinflammation. Recent studies have suggested a positive correlation between HE and AD. Some studies reported that an impaired cholesterol pathway, abnormal bile acid secretion, excessive ammonia level, impaired Aβ clearance, astrocytic dysfunction, and abnormal γ-aminobutyric acid GABAergic neuronal signaling in HE may also be involved in AD pathology. However, the mechanisms and related genes involved in AD-like pathology in the HE brain are unclear. Thus, we compared the cortical transcriptome profile between an HE mouse model, bile duct ligation (BDL), and an AD mouse model, the 5×FAD. Our study showed that the expression of many genes implicated in HE is associated with neuronal dysfunction in AD mice. We found changes in various protein-coding RNAs, implicated in synapses, neurogenesis, neuron projection, neuron differentiation, and neurite outgrowth, and non-coding RNAs possibly associated with neuropathology. Our data provide an important resource for further studies to elucidate AD-like pathophysiology in HE patients.