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1.
Psychol Med ; 53(13): 6037-6045, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36321391

RESUMO

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Eletroencefalografia , Risco , Fenômenos Magnéticos , Potenciais Evocados Auditivos/fisiologia
2.
Eur Arch Psychiatry Clin Neurosci ; 272(3): 359-370, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34652488

RESUMO

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Transtorno Bipolar/psicologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Transtornos Psicóticos/complicações , Fatores de Risco , Ideação Suicida , Tentativa de Suicídio/psicologia
3.
Age Ageing ; 51(2)2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35134842

RESUMO

BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.


Assuntos
Depressão , Carne , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Dieta/efeitos adversos , Comportamento Alimentar , Seguimentos , Humanos , Carne/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco
4.
Heart Fail Rev ; 25(5): 713-723, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31377979

RESUMO

Despite relative frequency of delirium in elderly hospitalized heart failure patients, skills and expertise in managing such complication are usually poor for physicians and nurses facing this clinical condition. International guidelines on heart failure do not provide detailed indication for such clinical condition, and evidence on this topic is limited. A multi-disciplinary approach (cardiologists, internists, geriatricians, psychologists, and psychiatrists) is often required; this review will therefore focus on diagnosis and clinical management of delirium in heart failure patients from a multidisciplinary point of view.


Assuntos
Delírio/etiologia , Insuficiência Cardíaca/complicações , Delírio/epidemiologia , Saúde Global , Insuficiência Cardíaca/psicologia , Humanos , Incidência
5.
Psychol Res ; 84(6): 1723-1728, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30949788

RESUMO

Studies on the effects of music on spatial reasoning report conflicting results. Some studies show slight effects, and others show no effects but few seem to replicate the strong findings of the first study published in Rauscher et al. Nature, 365(6447), 611-612, (1993). Nonetheless, the debate about the performance enhancing "Mozart effect" remains to be of great interest. In this study, we manipulated different physical parameters of sound traces (amplitude and frequency) to investigate whether particular dimensions may explain the enhancement effects found in spatial tasks following music listening. To this end, we asked 179 undergraduates and 183 older adults to listen to 5-min sound traces (Mozart KV 448, amplitude modulation tone, frequency modulation tone, white noise) and then complete a spatial reasoning task. In particular, results showed that repetitive frequency changes, as occurring in Mozart's melodies or in a frequency modulation tone, enhance performance.


Assuntos
Música , Resolução de Problemas , Estimulação Acústica , Idoso , Percepção Auditiva , Feminino , Humanos , Masculino , Tempo de Reação , Adulto Jovem
6.
Int J Geriatr Psychiatry ; 34(9): 1308-1315, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30136743

RESUMO

BACKGROUND: The prevalence of neuropsychiatric symptoms (NPS) diminishes the quality of life and increases the care burden in patients with dementia. Despite the clinical importance of dementia-associated NPS, no protocols for treating NPS are already well established. Attention has turned to the effectiveness of nonpharmacological treatments for NPS since their potential safe alternative to pharmacotherapy. OBJECTIVE: This study is aimed to compare the effects in older individuals with dementia living in a residential care, of two intervention programs, the gesture-verbal treatment (GVT), a treatment implemented by us on a previous method for word retrieval in individuals with aphasia, and the better-known doll therapy (DT). The GVT would act on both receptive and expressive language skills, the DT on attachment and emotional connections. METHODS: We evaluated NPS by the neuropsychiatric inventory in a total of 30 patients divided into 3 groups, the GVT, the DT, and control groups, using a pre-post design. The treatment groups completed 12-week nonpharmacological interventions in addition to standard rehabilitative therapies, while the control group participated only in standard rehabilitative therapies. RESULTS: The DT group showed significant improvements in agitation, irritability, apathy, depression, and delusions relative to controls. The GVT group showed significant improvements in apathy and depression with respect to controls. The DT intervention ameliorated symptoms of agitation compared to the GVT intervention whereas the GVT intervention improved apathy compared to the DT intervention. CONCLUSION: Improved understanding of the potential therapeutic benefits of different treatments for neuropsychiatric symptoms is crucial for establishing nonpharmacological interventions in dementia.


Assuntos
Terapia Comportamental/métodos , Demência/psicologia , Gestos , Transtornos Mentais/terapia , Jogos e Brinquedos , Agitação Psicomotora/terapia , Comportamento Verbal , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Apatia , Feminino , Humanos , Masculino , Transtornos Mentais/prevenção & controle , Prevalência , Qualidade de Vida
7.
J Nerv Ment Dis ; 204(3): 188-93, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26741464

RESUMO

Emotional face recognition is impaired in bipolar disorder, but it is not clear whether this is specific for the illness. Here, we investigated how aging and bipolar disorder influence dynamic emotional face recognition. Twenty older adults, 16 bipolar patients, and 20 control subjects performed a dynamic affective facial recognition task and a subsequent rating task. Participants pressed a key as soon as they were able to discriminate whether the neutral face was assuming a happy or angry facial expression and then rated the intensity of each facial expression. Results showed that older adults recognized happy expressions faster, whereas bipolar patients recognized angry expressions faster. Furthermore, both groups rated emotional faces more intensely than did the control subjects. This study is one of the first to compare how aging and clinical conditions influence emotional facial recognition and underlines the need to consider the role of specific and common factors in emotional face recognition.


Assuntos
Envelhecimento/fisiologia , Transtorno Bipolar/fisiopatologia , Expressão Facial , Reconhecimento Facial/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ira , Feminino , Felicidade , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Epigenomics ; : 1-13, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39400085

RESUMO

A complex interaction among sensory, social and epigenetic determinants in psychiatric conditions was described across all age strata. The high prevalence of mental disorders in individuals with sensory deficits might be attributed to the interaction among social isolation, cognitive functioning and sensory processing. The epigenetic implications of such interactions were examined: environmental and social factors can affect gene expression and impact the pathogenesis of psychiatric disorders also through sensory processing. This article discussed the role of social determinants, in other words, social isolation, loneliness and chronic stress, in promoting psychiatric disorders and, in a vicious circle, sensory deficits (vision, hearing, olfaction and somatosensation). We emphasized the importance of integrating social, sensory and epigenetic factors to target different treatments for psychiatric conditions.


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9.
J Alzheimers Dis ; 100(s1): S57-S61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39031368

RESUMO

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.


Assuntos
Apatia , Disfunção Cognitiva , Comportamento Social , Idoso , Humanos , Apatia/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Envelhecimento Cognitivo/fisiologia
10.
Life (Basel) ; 14(10)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39459516

RESUMO

BACKGROUND: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). METHODS: We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. RESULTS: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (ß = -1.05, p < 0.0001) and minor NCD (ß = -0.06, p < 0.01). In the fully adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (ß = 0.09, p < 0.001). The effect of loneliness on IADL (ß = -0.26, p < 0.0001) and ADL (ß = -0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: ß = 0.26, p < 0.0001; ADL: ß = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (ß = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. CONCLUSIONS: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

11.
Expert Opin Drug Discov ; 19(6): 639-647, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38685682

RESUMO

INTRODUCTION: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-ß (Aß), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aß clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aß monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results. AREAS COVERED: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU). EXPERT OPINION: Solanezumab was one of the first anti-Aß monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aß level by acting on soluble monomeric form of Aß peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aß cascade hypothesis of AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Humanos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Animais , Peptídeos beta-Amiloides/metabolismo , Camundongos , Falha de Tratamento , Progressão da Doença
12.
Psychiatry Res ; 342: 116189, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39321639

RESUMO

Anomalous Mismatch Negativity (MMN) in psychosis could be a consequence of disturbed neural oscillatory activity at sensory/perceptual stages of stimulus processing. This study investigated effective connectivity within and between the auditory regions during auditory odd-ball deviance tasks. The analyses were performed on two magnetoencephalography (MEG) datasets: one on duration MMN in a cohort with various diagnoses within the psychosis spectrum and neurotypical controls, and one on duration and pitch MMN in first-episode psychosis patients and matched neurotypical controls. We applied spectral Granger causality to MEG source-reconstructed signals to compute effective connectivity within and between the left and right auditory regions. Both experiments showed that duration-deviance detection was associated with early increases of effective connectivity in the beta band followed by increases in the alpha and theta bands, with the connectivity strength linked to the laterality of the MMN amplitude. Compared to controls, people with psychosis had overall smaller effective connectivity, particularly from left to right auditory regions, in the pathway where bilateral information converges toward lateralized processing, often rightward. Blunted MMN in psychosis might reflect a deficit in inter-hemispheric communication between auditory regions, highlighting a "dysconnection" already at preattentive stages of stimulus processing as a model system of widespread pathophysiology.

13.
Brain Sci ; 14(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38672016

RESUMO

Neuroticism is a personality trait associated with the risk of affective disorders and perinatal depression. We investigated the relationship between different levels of neuroticism, psychological characteristics, and depressive symptoms in a sample of pregnant women (N = 2631) who accessed the gynecology departments in the Puglia Region (Italy) from July 2020 to November 2022. Women were assessed for depressive symptoms and associated risk factors in their third trimester of pregnancy (T0) and after childbirth (T1), and followed-up at 6 months and 1 year after delivery if presenting signs of depression (T2-T3). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen depressive symptoms, and neuroticism was assessed through the subscales of the NEO Five Factor Inventory. Standardized measures of resilience, coping strategies, partner attachment, and quality of life were also employed. Higher levels of neuroticism were significantly associated with: (a) higher scores on the EPDS; (b) higher anxiety in the experience of close relationships; (c) lower psychological wellbeing; (d) lower levels of resilience; (e) lower levels of active coping; and (f) higher levels of self-blame. Our findings may suggest that neuroticism is a specific associated factor of perinatal depression and should be routinely assessed in the clinical screening of pregnant women in order to promote an early referral to psychological or psychiatric support services.

14.
J Clin Med ; 12(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37445551

RESUMO

(1) Background: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease. Fatigue is a prevalent and debilitating symptom that significantly impacts the quality of life of these patients. A relationship between personality traits and fatigue in MS has been hypothesized but not clearly defined. (2) Methods: A literature search was carried out from databases up to April 2023 for studies correlating personality traits and fatigue in patients suffering from MS. (3) Results: A total of ten articles was included; most of the studies depict a neuroticism-fatigue correlation; however, they were not consistent in terms of the fatigue, personality, and covariate assessments. (4) Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the link between personality traits and fatigue in MS. Several models of personality and different fatigue assessments have been found. Despite this, a common pathway shows that the neuroticism trait or similar personality patterns has a role in fatigue diagnosis. This may be a useful target to improve the quality of life and enhance the modification of the disease treatment results. Further homogeneous and longitudinal studies are needed.

15.
Expert Opin Investig Drugs ; 32(7): 625-634, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37405389

RESUMO

INTRODUCTION: Tauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e. Alzheimer's disease (AD), tau deposition can be observed, but tau coexists with another protein (amyloid-ß). In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy. AREAS COVERED: The present review summarized recent advances about the development and challenges in treatments for primary and secondary tauopathies, with a focus on passive tau-based immunotherapy. EXPERT OPINION: Several tau-targeted passive immunotherapeutics are in development for treating tauopathies. At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). However, none of these nine agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials.


Assuntos
Doença de Alzheimer , Paralisia Supranuclear Progressiva , Tauopatias , Humanos , Tauopatias/tratamento farmacológico , Tauopatias/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Anticorpos Monoclonais/uso terapêutico , Imunoterapia
16.
J Am Med Dir Assoc ; 24(5): 679-687, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36596468

RESUMO

OBJECTIVES: Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. DESIGN: Longitudinal population-based study with 8-year follow-up. SETTING AND PARTICIPANTS: We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study. METHODS: LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. RESULTS: The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months). CONCLUSIONS AND IMPLICATION: In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.


Assuntos
Disfunção Cognitiva , Depressão , Humanos , Idoso , Depressão/epidemiologia , Depressão/psicologia , Idade de Início , Seguimentos , Cognição
17.
Expert Opin Drug Discov ; 18(5): 515-526, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37042028

RESUMO

INTRODUCTION: Tauopathies represent clinicopathological entities with increased and abnormal glial and/or neuronal inclusions of tau, a microtubule-binding protein. Antisense oligonucleotides (ASOs) are a promising therapeutic approach for treating tauopathies as they can target tau mRNA to reduce total human tau expression or tau exon 10 expression and 4 R tau. Additionally, targeting the tau specifically with peptides may be a unique pharmacological approach, between small molecules and proteins. AREAS COVERED: The present review investigates the chemical basis of designing ASOs and peptides currently known to treat tauopathies. Among ASOs targeting tau expression, BIIB080 was the first to enter clinical trial development for treating mild Alzheimer's disease (AD). Furthermore, the therapeutic potential of peptide 021 (P021, Ac-DGGLAG-NH2) in tauopathies is discussed based on preclinical studies. EXPERT OPINION: ASOs are a promising therapeutic approach for tauopathies, particularly because ASOs may suppress the expression of harmful genes and are directly delivered to the brain, showing little systemic side effects. However, whether a generalized brain tau decrease will produce positive clinical effects remains unclear. A Phase II trial of BIIB080 is ongoing in mild AD. Neurotrophic and neurogenic peptide mimetic compounds have also shown potential as treatment options for AD and other tauopathies.


Assuntos
Doença de Alzheimer , Tauopatias , Humanos , Proteínas tau/metabolismo , Oligonucleotídeos/farmacologia , Tauopatias/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Peptídeos/farmacologia
18.
Schizophrenia (Heidelb) ; 9(1): 11, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36801866

RESUMO

Cognition and social cognition anomalies in patients with bipolar disorder (BD) and schizophrenia (SCZ) have been largely documented, but the degree of overlap between the two disorders remains unclear in this regard. We used machine learning to generate and combine two classifiers based on cognitive and socio-cognitive variables, thus delivering unimodal and multimodal signatures aimed at discriminating BD and SCZ from two independent groups of Healthy Controls (HC1 and HC2 respectively). Multimodal signatures discriminated well between patients and controls in both the HC1-BD and HC2-SCZ cohorts. Although specific disease-related deficits were characterized, the HC1 vs. BD signature successfully discriminated HC2 from SCZ, and vice-versa. Such combined signatures allowed to identify also individuals at First Episode of Psychosis (FEP), but not subjects at Clinical High Risk (CHR), which were classified neither as patients nor as HC. These findings suggest that both trans-diagnostic and disease-specific cognitive and socio-cognitive deficits characterize SCZ and BD. Anomalous patterns in these domains are also relevant to early stages of disease and offer novel insights for personalized rehabilitative programs.

19.
J Alzheimers Dis ; 94(3): 879-898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37355907

RESUMO

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Fragilidade , Humanos , Fragilidade/epidemiologia , Fragilidade/psicologia , Disfunção Cognitiva/epidemiologia , Fenótipo
20.
Brain Sci ; 13(7)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37508934

RESUMO

Peripartum depression (PPD) is a major complication of pregnancy, and numerous risk factors have been associated with its onset, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women's attachment style and depressive symptomatology in pregnancy and one week after giving birth in a large sample of women (N = 1664). Our hypothesis was that the relationship between anxious and avoidant attachment and depressive symptomatology would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), and Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment also has an indirect significant effect on postpartum depressive symptomatology through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depressive symptoms. Our findings revealed that not only is it important to consider attachment in understanding peripartum depressive symptomatology, but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

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