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1.
Psychol Med ; : 1-12, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563288

RESUMEN

BACKGROUND: The nature of the pathway from conduct disorder (CD) in adolescence to antisocial behavior in adulthood has been debated and the role of certain mediators remains unclear. One perspective is that CD forms part of a general psychopathology dimension, playing a central role in the developmental trajectory. Impairment in reflective functioning (RF), i.e., the capacity to understand one's own and others' mental states, may relate to CD, psychopathology, and aggression. Here, we characterized the structure of psychopathology in adult male-offenders and its role, along with RF, in mediating the relationship between CD in their adolescence and current aggression. METHODS: A secondary analysis of pre-treatment data from 313 probation-supervised offenders was conducted, and measures of CD symptoms, general and specific psychopathology factors, RF, and aggression were evaluated through clinical interviews and questionnaires. RESULTS: Confirmatory factor analyses indicated that a bifactor model best fitted the sample's psychopathology structure, including a general psychopathology factor (p factor) and five specific factors: internalizing, disinhibition, detachment, antagonism, and psychoticism. The structure of RF was fitted to the data using a one-factor model. According to our mediation model, CD significantly predicted the p factor, which was positively linked to RF impairments, resulting in increased aggression. CONCLUSIONS: These findings highlight the critical role of a transdiagnostic approach provided by RF and general psychopathology in explaining the link between CD and aggression. Furthermore, they underscore the potential utility of treatments focusing on RF, such as mentalization-based treatment, in mitigating aggression in offenders with diverse psychopathologies.

2.
Trials ; 25(1): 217, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532432

RESUMEN

BACKGROUND: Depression ranks as the foremost mental health concern among childbearing women. Within low- and middle-income countries (LMICs), between 20 and 25% of women encounter depression during pregnancy or soon after delivery. This condition impacts not only the mothers but also their offspring. Offspring of women suffering from postnatal depression (PND) exhibit suboptimal cognitive development and increased emotional and behavioural issues throughout their growth. This scenario becomes more pronounced in LMICs, where numerous adversities further jeopardise children's developmental progress. Despite antenatal services providing a pivotal platform to address women's mental health needs, PND treatment remains inaccessible in many LMICs. The World Health Organization advocates interpersonal psychotherapy (IPT) for treating depression. While research from high-income countries has established the efficacy of IPT and group-IPT (g-IPT) for PND, its effectiveness within the LMIC context and its potential benefits for child development remain uncharted. This study seeks to gauge the potency of g-IPT for women with PND in two LMICs. METHODS: This multi-site randomised controlled trial is a continuation of two preceding phases-conceptual mapping and a feasibility study executed in Lebanon and Kenya. Insights gleaned from these phases underpin this comprehensive RCT, which contrasts the efficacy and cost-effectiveness of high-quality standard care (HQ-SC) augmented with g-IPT against HQ-SC in isolation. The trial, characterised as an individually randomised superiority assessment, targets women with postnatal depression in Beirut, Lebanon, and Nairobi, Kenya. It aims to determine if culturally tailored g-IPT, administered within community settings in both countries, outperforms HQ-SC in influencing child developmental outcomes, maternal depression, and the quality of the mother-child bond. DISCUSSION: The SUMMIT trial, designed with pragmatism, possesses the magnitude to evaluate g-IPT within two LMIC frameworks. It seeks to enlighten policymakers, service commissioners, professionals, and users about g-IPT's potential to alleviate maternal PND and bolster child developmental outcomes in LMICs. Additionally, the trial will generate valuable data on the clinical and economic merits of high-quality standard care. TRIAL REGISTRATION: ISRCTN, ISRCTN15154316. Registered on 27 September 2023, https://doi.org/10.1186/ISRCTN15154316.


Asunto(s)
Depresión Posparto , Psicoterapia de Grupo , Femenino , Humanos , Depresión Posparto/terapia , Kenia , Líbano , Salud de la Mujer
3.
J Pers Disord ; 38(1): 10-18, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38324249

RESUMEN

This commentary reviews the Journal of Personality Disorders special issue "Interpersonal Trust and Borderline Personality Disorder: Insights From Clinical Practice and Research," published in Volume 37, Number 5, October 2023.


Asunto(s)
Trastorno de Personalidad Limítrofe , Confianza , Humanos , Trastornos de la Personalidad
4.
Dev Psychopathol ; : 1-10, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38389294

RESUMEN

In this paper, dedicated to Dante Cicchetti's contributions and enduring influence, we explore the prospective directions of developmental psychopathology. Our focus centers on key domains where Cicchetti's significant achievements have continually shaped our evolving thinking about psychological development. These domains include (a) the concepts of equifinality and multifinality, along with the challenges in predicting developmental trajectories, (b) the imperative to integrate wider sociocultural viewpoints into developmental psychopathology frameworks, (c) the interplay of genetic and environmental influences in developmental courses, (d) the significance of mental state language, and (e) the progress, or its absence, in the development of prevention and intervention tactics for children, adolescents, and their caregivers. While many of our forecasts regarding the future of developmental psychopathology may not materialize, we maintain optimistic that the essential ideas presented will influence the research agenda in this field and contribute to its growth over the next fifty years.

5.
Psychoanal Q ; 92(4): 599-640, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38095858

RESUMEN

We explore the interpersonal origins of human culture, arguing that culture emerges as a necessary consequence of our helplessness in infancy, which in turn requires a greater degree of collaboration and social organization than is necessary for other mammals. We propose a model of cultural transmission that depends on a dyadic interpersonal process whose vicissitudes can have a lifelong impact. We explore the role played by imagining subjectively experienced psychological states and processes in others, which we have defined as mentalizing, in the process of cultural transmission, and propose that mentalizing is key to the establishment of epistemic trust-that is to say, an experience of trust that enables the individual to absorb and use the knowledge they are being offered. We suggest that psychoanalysis can be viewed as a paradigmatic example of a process of transferring knowledge from one human being (the teacher, the caregiver, the analyst) to another (the learner, the young person, the patient) and argue that the mechanisms of psychic change in analysis cannot be fully understood without appreciating this aspect of the biological/evolutionary origins of our essential humanity. Finally, we discuss the clinical implications of the model we are proposing for the psychoanalytic process.


Asunto(s)
Cultura , Mentalización , Psicoanálisis , Teoría de la Mente , Confianza , Humanos , Emociones , Confianza/psicología
6.
Int J Psychoanal ; 104(6): 1063-1076, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38127476

RESUMEN

This paper argues that, despite its title, "The Ego and the Id" can be seen as the book of the superego, and although it is a metapsychological work, Freud's introduction of the new conceptual tools provided by the structural model was a response to the clinical problems he faced. The implications of Freud's introduction of the superego for the analytic relationship are discussed, with an attempt to deepen our understanding of what he had in mind by reading "Group Psychology and the Analysis of the Ego" alongside "The Ego and the Id". Finally, the paper draws on Bion to consider the implications of this remodelling of the analytic scene for listening and interpretation.


Asunto(s)
Ego , Teoría Freudiana , Masculino , Humanos , Superego
7.
Int J Psychoanal ; 104(5): 829-833, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37902477

Asunto(s)
Psicoanálisis , Humanos
8.
Health Promot Int ; 38(4)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37440253

RESUMEN

This paper seeks to explore how hospitals can be reconfigured to adopt more 'health-promoting' approaches and values. Specifically, the paper focuses on the role of hospital chaplaincy and argues that spiritual care should be considered alongside other health domains. Using semi-structured interviews, the aim of the paper is to explore the experiences of patients who accepted (n = 10) and declined (n = 10) hospital chaplaincy services. Data were analysed drawing on principles of interpretative phenomenological analysis (IPA). The findings suggested that participants who accessed chaplaincy services reported using the chaplains for pastoral, religious and spiritual care which contributed positively to their sense of well-being. This included religious rituals and supportive conversations. The majority of these participants had existing links with a faith institution. Participants who declined chaplaincy services reported having personal religious or spiritual beliefs. Other reasons cited, included: that the offer was made close to discharge; they had different support mechanisms; they were unaware of what the chaplaincy service offered. Participants identified a number of skills and attributes they associated with chaplains. They perceived them as being religious but available to all, somebody to talk to who was perceived as impartial with a shared knowledge and understanding. The paper concludes by highlighting the important role of chaplaincy as part of a holistic health-promoting hospital. This has implications not only for the design, delivery and promotion of chaplaincy services but also for health promotion more broadly to consider spiritual needs.


Asunto(s)
Cuidado Pastoral , Humanos , Encuestas y Cuestionarios , Hospitales , Espiritualidad , Inglaterra
9.
Int J Psychoanal ; 104(1): 147-152, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36799639

RESUMEN

This paper introduces the contributions of Alan Sugarman (US), Rachel Blass (Israel), Paul Denis (France), Luisa Perez (Uruguay), Bernard Reith (Switzerland) and David Tuckett (UK) to a debate on the question of how we can enable productive discussion about our scientific differences and why historically it has been so difficult for the discipline of psychoanalysis to initiate and sustain such discussions. By way of introduction the historical example of the Controversial Discussions in the British Psychoanalytic Society is briefly reviewed and several possible factors contributing to the difficulties are provisionally identified, including over-reliance on authority and tradition, eagerness to supervise on the basis of our own theoretical models rather than trying to understand those of others, the lack of clarity and consensus in our definitions of terms, a lack of mutual curiosity resulting in theoretical silos, an experienced threat to identity when adjustments to our positions are called for, and the lack of a methodology for undesrstanding and / or resolving differences.


Asunto(s)
Psicoanálisis , Terapia Psicoanalítica , Humanos , Francia , Israel
10.
Hippocampus ; 33(7): 811-829, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36808771

RESUMEN

A fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham-lesioned mice (n = 6) following 90° rotations of either distal landmarks or proximal cues in a cue- controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham-lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway.


Asunto(s)
Corteza Entorrinal , Células de Lugar , Ratones , Animales , Corteza Entorrinal/patología , Hipocampo/patología , Vías Nerviosas , Señales (Psicología)
11.
Res Sports Med ; 31(4): 416-439, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34711091

RESUMEN

Kinesio taping is widely used in musculoskeletal conditions. We performed a systematic review and meta-analysis on the efficacy of kinesio taping in musculoskeletal disorders compared to other interventions. Twelve electronic databases were used for systemic search and data relevant to pain and disability were extracted. The protocol was registered in PROSPERO (CRD42018087606). Meta-analysis was performed to compare the efficacy of kinesio taping to other modalities of musculoskeletal disorders. As a result, 36 studies were included in the quantitative analysis. Kinesio taping was found to provide an improvement of both pain and disability when applied to any region of the body. In the first five days of application, kinesio taping significantly reduced the pain in all body regions (SMD = -0.63, 95%CI: -0.87, -0.39). This was also noted after four-to-six weeks of application (SMD = -0.76, 95%CI: -1.07, -0.45). When kinesio taping was used for disability in low back pain patients, it significantly reduced the disability within five days of application (SMD = -0.70, 95%CI: -1.29, -0.11). Finally, kinesio taping has shown an improvement of the disability in all body regions after four-to-six weeks of application (SMD = -0.59, 95%CI: -0.96, -0.22). Our findings support kinesio taping as an adjuvant to other treatments for musculoskeletal disorders. Abbreviations KT = Kinesio taping; MSK = musculoskeletal; SD = standard deviation; CR = conventional rehabilitation; NDI = Neck Disability Index; NPS = Numerical Pain Scale; CTM = Cervical Thrust Manipulation; PIR = Post-isometric muscle relaxation; NPRS Numerical Pain Rating Scale; OA = osteoarthritis; ROM = Range of motion; VAS = visual analogue scale; VAS-W = visual analogue scale-worst pain; VAS-U = visual analogue scale-usual pain; VAS-R = visual analogue scale-resting pain; VAS-A = visual analogue scale-activity pain; VAS-N = visual analogue scale-night pain; NPDS = Neck Pain Disability Scale; QA = Quality assessment.


Asunto(s)
Cinta Atlética , Personas con Discapacidad , Dolor de la Región Lumbar , Enfermedades Musculoesqueléticas , Humanos , Enfermedades Musculoesqueléticas/terapia , Dolor de la Región Lumbar/terapia , Rango del Movimiento Articular
12.
Dev Psychopathol ; 34(4): 1205-1220, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-33766162

RESUMEN

This paper proposes a model for developmental psychopathology that is informed by recent research suggestive of a single model of mental health disorder (the p factor) and seeks to integrate the role of the wider social and cultural environment into our model, which has previously been more narrowly focused on the role of the immediate caregiving context. Informed by recently emerging thinking on the social and culturally driven nature of human cognitive development, the ways in which humans are primed to learn and communicate culture, and a mentalizing perspective on the highly intersubjective nature of our capacity for affect regulation and social functioning, we set out a cultural-developmental approach to psychopathology.


Asunto(s)
Trastornos Mentales , Aprendizaje Social , Cognición , Humanos , Aprendizaje , Trastornos Mentales/psicología , Psicopatología
13.
PLoS One ; 16(4): e0250264, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33861805

RESUMEN

Epistemic trust (ET) refers to trust in communicated knowledge. This paper describes the development and validation of a new self-report questionnaire, the Epistemic Trust, Mistrust and Credulity Questionnaire (ETMCQ). We report on two studies (Study 1, n = 500; Study 2, n = 705) examining the psychometric properties of the ETMCQ and the relationship between EMTCQ scores (i.e., an individual's epistemic stance) and exposure to adverse childhood experiences, mental health symptoms, attachment, mentalizing and general self-efficacy. The factor structure of the ETMCQ was examined using Exploratory and Confirmatory Factor Analyses, and its reliability and test-retest reliability were tested. Both studies yielded three correlated yet distinct factors-Trust, Mistrust and Credulity-and confirmed the reliability and validity of the ETMCQ. Preregistered hypotheses were confirmed and replicated across both studies. Main findings suggest intriguing links between the ETMCQ and developmental psychopathology constructs and are consistent with thinking on the role of epistemic stance in undermining adaptation and increasing the developmental risk of mental health problems. Mistrust and Credulity scores were associated with childhood adversity and higher scores on the global psychopathology severity index and both factors partially mediated the link between early adversity and mental health symptoms. Mistrust and Credulity were positively associated with difficulties in understanding mental states and insecure attachment styles. Post-hoc analysis identified that different attachment styles were associated with differences in epistemic stance. In addition, Trust was not associated with reduced levels of mental health symptoms and did not moderate the impact of childhood adversity-findings are congruent with the suggestion that the reduction of mistrust and credulity may be crucial common factors in promoting resilience and the effectiveness of psychotherapeutic interventions. This investigation and the ETMCQ provide an empirical measure of what until now has been largely a theoretical concept and open new avenues for future research.


Asunto(s)
Experiencias Adversas de la Infancia/psicología , Conocimiento , Salud Mental , Mentalización , Autoinforme , Confianza/psicología , Adulto , Humanos , Encuestas y Cuestionarios
14.
PLoS One ; 15(11): e0236525, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33196654

RESUMEN

BACKGROUND: Over 600 RCTs have demonstrated the effectiveness of psychosocial interventions for children and young people's mental health, but little is known about the long-term outcomes. This systematic review sought to establish whether the effects of selective and indicated interventions were sustained at 12 months. METHOD: We conducted a systematic review and meta-analysis focusing on studies reporting medium term outcomes (12 months after end of intervention). FINDINGS: We identified 138 trials with 12-month follow-up data, yielding 165 comparisons, 99 of which also reported outcomes at end of intervention, yielding 117 comparisons. We found evidence of effect relative to control at end of intervention (K = 115, g = 0.39; 95% CI: 0.30-0.47 I2 = 84.19%, N = 13,982) which was maintained at 12 months (K = 165, g = 0.31, CI: 0.25-0.37, I2 = 77.35%, N = 25,652) across a range of diagnostic groups. We explored the impact of potential moderators on outcome, including modality, format and intensity of intervention, selective or indicated intervention, site of delivery, professional/para-professional and fidelity of delivery. We assessed both risk of study bias and publication bias. CONCLUSIONS: Psychosocial interventions provided in a range of settings by professionals and paraprofessionals can deliver lasting benefits. High levels of heterogeneity, moderate to high risk of bias for most studies and evidence of publication bias require caution in interpreting the results. Lack of studies in diagnostic groups such as ADHD and self-harm limit the conclusions that can be drawn. Programmes that increase such interventions' availability are justified by the benefits to children and young people and the decreased likelihood of disorder in adulthood.


Asunto(s)
Trastornos Mentales/terapia , Salud Mental , Intervención Psicosocial/métodos , Psicoterapia/métodos , Adolescente , Adulto , Niño , Humanos , Pronóstico , Adulto Joven
15.
Lancet Psychiatry ; 7(5): 420-430, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32353277

RESUMEN

BACKGROUND: Multisystemic therapy is a manualised treatment programme for young people aged 11-17 years who exhibit antisocial behaviour. To our knowledge, the Systemic Therapy for At Risk Teens (START) trial is the first large-scale randomised controlled trial of multisystemic therapy in the UK. Previous findings reported to 18 months after baseline (START-I study) did not indicate superiority of multisystemic therapy compared with management as usual. Here, we report outcomes of the trial to 60 months (START-II study). METHODS: In this pragmatic, randomised, controlled, superiority trial, young people (aged 11-17 years) with moderate-to-severe antisocial behaviour were recruited from social services, youth offending teams, schools, child and adolescent mental health services, and voluntary services across England, UK. Participants were eligible if they had at least three severity criteria indicating past difficulties across several settings and one of five general inclusion criteria for antisocial behaviour. Eligible families were randomly assigned (1:1), using stochastic minimisation and stratifying for treatment centre, sex, age at enrolment, and age at onset of antisocial behaviour, to management as usual or 3-5 months of multisystemic therapy followed by management as usual. Research assistants and investigators were masked to treatment allocation; the participants could not be masked. For this extension study, the primary outcome was the proportion of participants with offences with convictions in each group at 60 months after randomisation. This study is registered with ISRCTN, ISRCTN77132214, and is closed to accrual. FINDINGS: Between Feb 4, 2010, and Sept 1, 2012, 1076 young people and families were assessed for eligibility and 684 were randomly assigned to management as usual (n=342) or multisystemic therapy (n=342). By 60 months' of follow-up, 188 (55%) of 342 people in the multisystemic therapy group had at least one offence with a criminal conviction, compared with 180 (53%) of 341 in the management-as-usual group (odds ratio 1·13, 95% CI 0·82-1·56; p=0·44). INTERPRETATION: The results of the 5-year follow-up show no evidence of longer-term superiority for multisystemic therapy compared with management as usual. FUNDING: National Institute for Health Research Health Services and Delivery Research programme.


Asunto(s)
Conducta del Adolescente , Comunicación , Trastorno de la Conducta/rehabilitación , Crimen/estadística & datos numéricos , Terapia Familiar/métodos , Delincuencia Juvenil/rehabilitación , Responsabilidad Parental , Apoyo Social , Adaptación Psicológica , Adolescente , Terapia de Manejo de la Ira , Trastorno de Personalidad Antisocial , Niño , Inglaterra , Femenino , Visita Domiciliaria , Humanos , Masculino , Relaciones Padres-Hijo , Red Social , Resultado del Tratamiento
16.
Annu Rev Clin Psychol ; 16: 297-325, 2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32023093

RESUMEN

Mentalizing is the capacity to understand others and oneself in terms of internal mental states. It is assumed to be underpinned by four dimensions: automatic-controlled, internally-externally focused, self-other, and cognitive-affective. Research suggests that mental disorders are associated with different imbalances in these dimensions. Addressing the quality of mentalizing as part of psychosocial treatments may benefit individuals with various mental disorders. We suggest that mentalizing is a helpful transtheoretical and transdiagnostic concept to explain vulnerability to psychopathology and its treatment. This review summarizes the mentalizing approach to psychopathology from a developmental socioecological evolutionary perspective. We then focus on the application of the mentalizing approach to personality disorders, and we review studies that have extended this approach to other types of psychopathology, including depression, anxiety, and eating disorders. We summarize core principles of mentalization-based treatments and preventive interventions and the evidence for their effectiveness. We conclude with recommendations for future research.


Asunto(s)
Trastornos Mentales/fisiopatología , Trastornos Mentales/terapia , Mentalización/fisiología , Psicoterapia , Humanos , Trastornos Mentales/prevención & control
17.
Psychol Med ; 50(6): 1010-1019, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31084635

RESUMEN

BACKGROUND: Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated. METHODS: 147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion. RESULTS: The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes. CONCLUSIONS: DIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs.


Asunto(s)
Trastorno Depresivo Mayor/terapia , Atención Primaria de Salud/estadística & datos numéricos , Psicoterapia Psicodinámica/métodos , Adulto , Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Inglaterra , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto Joven
18.
Front Immunol ; 10: 2780, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31849963

RESUMEN

CX3CR1 is a chemokine receptor expressed on microglia that binds Fractalkine (CX3CL1) and regulates microglial recruitment to sites of neuroinflammation. Full deletion of CX3CR1 in mouse models of Alzheimer's disease have opposing effects on amyloid-ß and tau pathologies raising concerns about the benefits of targeting CX3CR1 for treatment of this disease. Since most therapies achieve only partial blockade of their targets, we investigated the effects of partial CX3CR1 deficiency on the development and progression of amyloid-ß deposition in the PS1-APP Alzheimer's mouse model. We generated PS1-APP mice heterozygous for CX3CR1 (PS1-APP-CX3CR1+/-) and analyzed these mice for Alzheimer's-like pathology. We found that partial CX3CR1 deficiency was associated with a significant reduction in Aß levels and in senile-like plaque load in the brain as compared with age-matched PS1-APP mice. Reduced Aß level in the brain was associated with improved cognitive function. Levels of the neuronal-expressed Aß-degrading enzymes insulysin and matrix metalloproteinase 9, which are reduced in the brains of regular PS1-APP mice, were significantly higher in PS1-APP-CX3CR1+/- mice. Our data indicate that lowering CX3CR1 levels or partially inhibiting its activity in the brain may be a therapeutic strategy to increase neuronal Aß clearance, reduce Aß levels and delay progression of Alzheimer's-Like disease. Our findings also suggest a novel pathway where microglial CX3CR1 can regulates gene expression in neurons.


Asunto(s)
Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Receptor 1 de Quimiocinas CX3C/deficiencia , Heterocigoto , Microglía/metabolismo , Neuronas/metabolismo , Transducción de Señal , Enfermedad de Alzheimer/patología , Animales , Conducta Animal , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos
19.
Cell Rep ; 29(11): 3592-3604.e5, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31825838

RESUMEN

A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aß) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aß-induced pathology. We find that Aß and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function. In both our mouse model and human postmortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau reduction in the mice initiated after behavioral deficits emerge corrects behavioral deficits, reduces synaptic tau levels, and substantially reverses transcriptional perturbations, suggesting that lowering synaptic tau levels may be beneficial in AD.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Animales , Femenino , Humanos , Masculino , Ratones , Microglía/metabolismo , Conducta Espacial , Sinapsis/metabolismo , Transcriptoma
20.
Psychopathology ; 52(2): 94-103, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31362289

RESUMEN

This paper seeks to elucidate the phenomenological experience of psychotherapy in the context of the theory of mentalizing and epistemic trust. We describe two related phenomenological experiences that are the domain of psychotherapeutic work. The first is the patient's direct experience of their own personal narrative being recognized, marked and reflected back to them by the therapist. Secondly, this intersubjective recognition makes possible the regulation and alignment of the patient's imaginative capacity in relation to phenomenological experiences. In describing three aspects of the communication process that unfold in effective psychotherapeutic interventions - (1) the epistemic match, (2) improving mentalizing and (3) the re-emergence of social learning - the way in which any effective treatment is embedded in metacognitive processes about the self in relation to perceptual social reality is explained. In particular, attention is drawn to wider social determinants of psychopathology. We discuss the possible mechanism for the relationship between the socioeconomic environment and psychopathology, and the implications of this for psychotherapeutic treatment.


Asunto(s)
Psicoterapia/métodos , Confianza/psicología , Humanos , Resultado del Tratamiento
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