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1.
Schizophrenia (Heidelb) ; 8(1): 41, 2022 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-35853871

RESUMEN

Although epidemiological studies report that hallucinations occur in 6-15% of the general population, little is known about their phenomenology. To overcome this paucity, this study investigates the phenomenological characteristics of hallucinations in the general population, by using a nationally promoted online survey to assess hallucination phenomenology in four sensory modalities, through a self-report version of the Questionnaire for Psychotic Experiences (QPE), in 10,448 participants (aged 14-88 years). The phenomenology of hallucinations was assessed if hallucinations reportedly occurred in the past month. In the past month, auditory hallucinations were reported most frequently (29.5%), followed by visual (21.5%), tactile (19.9%), and olfactory hallucinations (17.3%); hallucinations in two or more modalities were reported by 47.6%. Substantial numbers of participants rated their hallucinations as severe, due to negative content (16.0-31.6%), previous bothersome experiences (14.8-20.2%), ensuing distress (10.5-16.8%), and/or ensuing disfunctioning (12.7-17.3%). Decreased insight was found in 10.2-11.4%. Hypnagogia was reported by 9.0-10.6%, and bereavement hallucinations by 2.8%. Despite a low prevalence of delusions (7.0%), these phenomena were significantly associated with recent hallucinations, observed in up to 13.4% of the participants with hallucinations during the past week (p < 0.001). Our results indicate a wide variety of the phenomenology of hallucinations in the general population and support the existence of a phenomenological continuum.

2.
Psychiatry Res Neuroimaging ; 317: 111384, 2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34537602

RESUMEN

The subventricular zone (SVZ) of the lateral ventricles harbors neuronal stem cells in adult mammals. Rodent studies report neurogenic effects in the SVZ of electroconvulsive stimulation. We hypothesize that if this finding translates to depressed patients undergoing electroconvulsive therapy (ECT), this would be reflected in shape changes at the SVZ. Using T1-weighted MR images acquired at ultra-high field strength (7T), the shape and volume of the ventricles were compared from pre to post ECT after 10 ECT sessions (in patients twice weekly) or 5 weeks apart (controls) using linear mixed models with age and gender as covariates. Ventricle shape significantly changed and volume significantly decreased over time in patients for the left ventricle, but not in controls. The decrease in volume of the ventricles was associated to a decrease in depression scores, and an increase in the left dentate gyrus, However, the shape changes of the ventricles were not restricted to the neurogenic niche in the lateral walls of the ventricles, providing no clear evidence for neurogenesis as sole explanation of volume changes in the ventricles after ECT.


Asunto(s)
Terapia Electroconvulsiva , Ventrículos Laterales , Animales , Terapia Electroconvulsiva/métodos , Humanos , Ventrículos Laterales/diagnóstico por imagen , Imagen por Resonancia Magnética , Mamíferos , Neurogénesis/fisiología , Neuronas
3.
Contemp Clin Trials Commun ; 20: 100681, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33364517

RESUMEN

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

4.
Psychiatry Res ; 292: 113314, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32731082

RESUMEN

Although psychotic experiences are prevalent across many psychiatric, neurological, and medical disorders, investigation of these symptoms has largely been restricted to diagnostic categories. This study aims to examine phenomenological similarities and differences across a range of diagnoses. We assessed frequency, severity and phenomenology of psychotic experiences in 350 outpatients including; participants with schizophrenia spectrum disorders, hearing impairment, Parkinson's disease, Lewy Body Dementia, Alzheimer's disease, visual impairment, posttraumatic stress disorder, borderline personality disorder, and participants with recent major surgery. Psychotic phenomena were explored between these groups using the Questionnaire for Psychotic Experiences (QPE). Participants with major psychiatric disorders reported a combination of several psychotic experiences, and more severe experiences compared to all other disorders. Participants with recent major surgery or visual impairment experienced isolated visual hallucinations. Participants with hearing impairment reported isolated auditory hallucinations, whereas the neurodegenerative disorders reported visual hallucinations, occasionally in combination with hallucinations in another modality or delusions. The phenomenology between neurodegenerative disorders, and within major psychiatric disorders showed many similarities. Our findings indicate that the phenomenology of psychotic experiences is not diagnosis specific, but may rather point to the existence of various subtypes across diagnoses. These subtypes could have a different underlying etiology requiring specific treatment.


Asunto(s)
Alucinaciones/diagnóstico , Alucinaciones/psicología , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/psicología , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/psicología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Esquizofrenia/diagnóstico , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología
5.
Brain Stimul ; 13(4): 1080-1086, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32360430

RESUMEN

BACKGROUND: Volume increases of the hippocampus after electroconvulsive therapy (ECT) are a robust finding, pointing into the direction of neurogenesis. However, such volumetric increases could also be explained by edema and/or neuroplastic changes (such as angiogenesis). OBJECTIVES: If edema explains the volume increase of the hippocampus we hypothesize it would lead to increased mean diffusivity (MD). If neuroplastic would explain the volume increase, it would lead to decreased MD. To investigate angiogenesis as explanation we studied the perfusion fraction f and the pseudodiffusion component D∗ obtained from intravoxel incoherent motion (IVIM) data, and relative perfusion changes obtained from arterial spin labelling (ASL) data. METHODS: Using ultra-high field (7 tesla) MRI we acquired IVIM and ASL data. We compared MD, f, D∗ and ASL values for both hippocampi in 21 patients (before and after 10 ECT sessions) and 8 healthy controls (without ECT) in a linear mixed model adjusting for age and gender. RESULTS: We found a significant decrease in MD (which was absent in the healthy controls) in the left and right hippocampus (t = -3.98, p < 0.001). In addition, a decrease in f (t = -4.61, p < 0.001, but not in controls) and no differences in D∗ or ASL perfusion values (both p > 0.05) were found. CONCLUSIONS: The decrease in MD in perfusion fraction f suggest that formation of edema nor angiogenesis are responsible for the ECT-induced volume increases in the hippocampus. Also, it supports the hypothesis that hippocampal volume increases might be due to neuroplastic changes.


Asunto(s)
Edema/diagnóstico por imagen , Terapia Electroconvulsiva/métodos , Hipocampo/fisiopatología , Plasticidad Neuronal , Adulto , Edema/etiología , Terapia Electroconvulsiva/efectos adversos , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Movimiento (Física)
6.
Mol Psychiatry ; 25(7): 1559-1568, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-30867562

RESUMEN

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its working mechanism remains unclear. In the animal analog of ECT, neurogenesis in the dentate gyrus (DG) of the hippocampus is observed. In humans, volume increase of the hippocampus has been reported, but accurately measuring the volume of subfields is limited with common MRI protocols. If the volume increase of the hippocampus in humans is attributable to neurogenesis, it is expected to be exclusively present in the DG, whereas other processes (angiogenesis, synaptogenesis) also affect other subfields. Therefore, we acquired an optimized MRI scan at 7-tesla field strength allowing sensitive investigation of hippocampal subfields. A further increase in sensitivity of the within-subjects measurements is gained by automatic placement of the field of view. Patients receive two MRI scans: at baseline and after ten bilateral ECT sessions (corresponding to a 5-week interval). Matched controls are also scanned twice, with a similar 5-week interval. A total of 31 participants (23 patients, 8 controls) completed the study. A large and significant increase in DG volume was observed after ECT (M = 75.44 mm3, std error = 9.65, p < 0.001), while other hippocampal subfields were unaffected. We note that possible type II errors may be present due to the small sample size. In controls no changes in volume were found. Furthermore, an increase in DG volume was related to a decrease in depression scores, and baseline DG volume predicted clinical response. These findings suggest that the volume change of the DG is related to the antidepressant properties of ECT, and may reflect neurogenesis.


Asunto(s)
Giro Dentado , Depresión/patología , Depresión/terapia , Terapia Electroconvulsiva , Tamaño de los Órganos , Giro Dentado/citología , Giro Dentado/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
7.
Schizophr Bull ; 45(45 Suppl 1): S78-S87, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30715541

RESUMEN

Psychotic experiences are prevalent across a wide variety of psychiatric, neurological, and medical conditions. Yet current assessments are often designed for one disorder, or are limited in their examination of phenomenological features; this has hindered transdiagnostic research. This article describes an examination of the validity and reliability of the English version of a new assessment, the Questionnaire for Psychotic Experiences (QPE). This study aimed to use the QPE to examine hallucinations and delusions across a number of different conditions, and to ensure that the QPE had acceptable psychometric properties. An International Consortium on Hallucination Research working group, along with consumer groups, developed the 50-item QPE to assess the presence, severity, and phenomenology of hallucinations and delusions. Participants in the study who reported psychotic experiences included those with schizophrenia, schizoaffective disorder, bipolar affective disorder, and major depressive disorder, and those without a need for care (ie, nonclinical participants). There were 173 participants in total. Convergent and discriminant validity were assessed. Reliability was examined in terms of stability, equivalence, and internal consistency. The data confirmed that the QPE had good psychometric properties and could be put forward as an accepted measure of the transdiagnostic evaluation of psychotic experiences. Further validation is recommended with neurological and medical populations. Given its validity and reliability, comprehensive evaluation of psychotic phenomena, and relatively quick administration time, we propose that the QPE is a valuable instrument for both clinical and research settings.


Asunto(s)
Trastorno Bipolar/diagnóstico , Deluciones/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Alucinaciones/diagnóstico , Escalas de Valoración Psiquiátrica/normas , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Trastorno Bipolar/complicaciones , Deluciones/etiología , Trastorno Depresivo Mayor/complicaciones , Femenino , Alucinaciones/etiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/complicaciones , Reproducibilidad de los Resultados , Esquizofrenia/complicaciones , Adulto Joven
8.
J Affect Disord ; 238: 659-665, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-29966930

RESUMEN

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from major depression. However, its use is limited due to concerns about negative effects on cognition. Unilateral ECT is associated with transient cognitive side-effects, while case-controlled studies investigating the effect of bilateral ECT on cognition remain scarce. We investigate the effects of bilateral ECT on cognition in depression in a longitudinal case-controlled study. We hypothesize that adverse cognitive effects of bilateral ECT are transient rather than long-term. METHODS: A total of 48 depressed patients and 19 controls were included in the study and assessed with a battery of cognitive tests, including tests of: working memory, verbal fluency, visuospatial abilities, verbal/visual memory and learning, processing speed, inhibition, attention and task-switching, and premorbid IQ. Patients underwent three cognitive assessments: at baseline (n = 43), after ten ECT sessions (post-treatment; n = 39) and six months after the tenth ECT session (follow-up; n = 25). Healthy controls underwent the same cognitive assessment at baseline and after five-weeks. RESULTS: Within the patient group, transient adverse cognitive side-effects were observed for verbal memory and learning, and verbal fluency. None of the cognitive domains tested in this study showed persisting impairments. LIMITATIONS: A relatively high attrition rate is observed and autobiographical memory was not assessed. CONCLUSION: This study shows that bilateral ECT has negative cognitive effects on short-term. These effects could be explained by a decrease in cognitive performance, a lack of learning effects or a combination. However, the decrease in cognitive functioning appears to recover after six months.


Asunto(s)
Trastornos del Conocimiento/etiología , Cognición , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/efectos adversos , Adulto , Estudios de Casos y Controles , Trastornos del Conocimiento/psicología , Trastorno Depresivo Mayor/psicología , Terapia Electroconvulsiva/métodos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tiempo , Factores de Tiempo , Resultado del Tratamiento
9.
Neuroimage Clin ; 14: 422-432, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28275543

RESUMEN

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.


Asunto(s)
Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Cooperación Internacional , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales/estadística & datos numéricos , Trastorno Depresivo Mayor/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
10.
J Clin Exp Neuropsychol ; 39(3): 231-241, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27618141

RESUMEN

INTRODUCTION: Rule induction tests such as the Wisconsin Card Sorting Test require executive control processes, but also the learning and memorization of simple stimulus-response rules. In this study, we examined the contribution of diminished learning and memorization of simple rules to complex rule induction test performance in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's dementia (AD). METHOD: Twenty-six aMCI patients, 39 AD patients, and 32 control participants were included. A task was used in which the memory load and the complexity of the rules were independently manipulated. This task consisted of three conditions: a simple two-rule learning condition (Condition 1), a simple four-rule learning condition (inducing an increase in memory load, Condition 2), and a complex biconditional four-rule learning condition-inducing an increase in complexity and, hence, executive control load (Condition 3). RESULTS: Performance of AD patients declined disproportionately when the number of simple rules that had to be memorized increased (from Condition 1 to 2). An additional increment in complexity (from Condition 2 to 3) did not, however, disproportionately affect performance of the patients. Performance of the aMCI patients did not differ from that of the control participants. In the patient group, correlation analysis showed that memory performance correlated with Condition 1 performance, whereas executive task performance correlated with Condition 2 performance. CONCLUSIONS: These results indicate that the reduced learning and memorization of underlying task rules explains a significant part of the diminished complex rule induction performance commonly reported in AD, although results from the correlation analysis suggest involvement of executive control functions as well. Taken together, these findings suggest that care is needed when interpreting rule induction task performance in terms of executive function deficits in these patients.


Asunto(s)
Enfermedad de Alzheimer/psicología , Amnesia/psicología , Disfunción Cognitiva/psicología , Función Ejecutiva/fisiología , Aprendizaje/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Memoria/fisiología , Pruebas Neuropsicológicas , Análisis y Desempeño de Tareas
12.
Neurosci Biobehav Rev ; 62: 1-20, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26743858

RESUMEN

Several studies suggest hearing impairment as a risk factor for psychosis. Hearing impairment is highly prevalent and potentially reversible, as it can be easily diagnosed and sometimes improved. Insight in the association between hearing impairment and psychosis can therefore contribute to prevention of psychosis. This paper provides meta-analyses of all epidemiologic evidence on the association between hearing impairment and psychosis and summarizes mechanisms that potentially underlie this relationship. Meta-analyses showed an increased risk of hearing impairment on all psychosis outcomes, such as hallucinations (OR 1.40(95%CI 1.18-1.65; n=227,005)), delusions (OR 1.55(95%CI 1.36-1.78; n=250,470)), psychotic symptoms (OR 2.23(95%CI 1.83-2.72; n=229,647) and delirium (OR 2.67(95%CI 2.05-3.48; n=12,432). Early exposure to hearing impairment elevated the risk of later development of schizophrenia (OR 3.15(95%CI 1.25-7.95; n=50,490)). Potential mechanisms underlying this association include loneliness, diminished theory of mind, disturbances of source monitoring and top-down processing and deafferentiation. Early assessment and treatment of hearing impairment in patients with (high risk of) psychosis may be essential in psychosis treatment and prevention.


Asunto(s)
Deluciones/fisiopatología , Alucinaciones/etiología , Pérdida Auditiva/complicaciones , Trastornos Psicóticos/complicaciones , Esquizofrenia/complicaciones , Alucinaciones/complicaciones , Humanos , Factores de Riesgo
13.
Schizophr Bull ; 42(3): 588-99, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26547223

RESUMEN

BACKGROUND: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. METHODS: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges' g. RESULTS: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges' g = .39, P < .001), positive (k = 15, n = 715: Hedges' g = .32, P < .01), negative (k = 18, n = 854: Hedges' g = .49, P < .001), and general (k = 10, n = 475: Hedges' g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges' g = .55, P < .001), global functioning (k = 5, n = 342: Hedges' g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges' g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges' g = .32, P < .05), while exercise in general or in any other form had no effect on cognition. CONCLUSION: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga.


Asunto(s)
Disfunción Cognitiva/rehabilitación , Depresión/terapia , Terapia por Ejercicio/métodos , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Esquizofrenia/rehabilitación , Disfunción Cognitiva/etiología , Depresión/etiología , Humanos , Esquizofrenia/complicaciones
14.
J Clin Exp Neuropsychol ; 37(5): 538-48, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26011711

RESUMEN

INTRODUCTION: Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present study, we examined WM and episodic memory formation in normal aging and in patients with early Alzheimer's disease (mild cognitive impairment, MCI; and Alzheimer's dementia, AD). METHOD: In the first study, 26 young adults (mean age 29.6 years) were compared to 18 middle-aged adults (mean age 52.2 years) and 25 older adults (mean age 72.8 years). We used an associative delayed-match-to-sample WM task, which requires participants to maintain two pairs of faces and houses presented on a computer screen for short (3 s) or long (6 s) maintenance intervals. After the WM task, an unexpected subsequent associative memory task was administered (two-alternative forced choice). In the second study, 27 patients with AD and 19 patients with MCI were compared to 25 older controls, using the same paradigm as that in Experiment 1. RESULTS: Older adults performed worse than both middle-aged and young adults. No effect of delay was observed in the healthy adults, and pairs that were processed during long maintenance intervals were not better remembered in the subsequent memory task. In the MCI and AD patients, longer maintenance intervals hampered the task performance. Also, both patient groups performed significantly worse than controls on the episodic memory task as well as the associative WM task. CONCLUSIONS: Aging and AD present with a decline in WM binding, a finding that extends similar results in episodic memory. Longer delays in the WM task did not affect episodic memory formation. We conclude that WM deficits are found when WM capacity is exceeded, which may occur during associative processing.


Asunto(s)
Envejecimiento , Enfermedad de Alzheimer/complicaciones , Disfunción Cognitiva/complicaciones , Trastornos de la Memoria/etiología , Memoria Episódica , Memoria a Corto Plazo/fisiología , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Aprendizaje Verbal/fisiología
15.
Schizophr Res ; 168(3): 603-13, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25914107

RESUMEN

INTRODUCTION: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in the treatment of schizophrenia is summarized. METHODS: Double-blind, placebo-controlled, randomized studies were included, examining augmentation with estrogens, selective estrogen receptor modulators (SERMs), testosterone, dehydroepiandrosterone (DHEA), pregnenolone, and oxytocin. Outcome measures were total symptom severity, positive and negative symptom subscores, and cognition. In meta-analyses, combined weighted effect sizes (Hedges' g) per hormone were calculated. RESULTS: Twenty-four studies were included, examining 1149 patients. Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001). Subgroup analyses yielded significant results for estrogens in premenopausal women (k=6) for total, positive, and negative symptoms, and for the SERM raloxifene in postmenopausal women (k=3) for total and negative, but not positive symptoms. Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027). No overall effects were found for DHEA (k=4), pregnenolone (k=4), and oxytocin (k=6). Results for cognition (k=12) were too diverse for meta-analyses, and inspection of these data showed no consistent benefit. CONCLUSIONS: Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account. Future trials are needed to study long-term effects and effects on cognition.


Asunto(s)
Antipsicóticos/uso terapéutico , Hormonas Gonadales/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Oxitocina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Neurobiol Aging ; 35(9): 2039-45, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24684788

RESUMEN

We compared hippocampal subfield and entorhinal cortex (ERC) volumes between patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and controls without cognitive impairment. Additionally, we investigated the relation between age and hippocampal subfields and ERC in controls. We performed ultra-high field 0.7 mm(3) 7Tesla magnetic resonance imaging in 16 patients with amnestic MCI, 9 with AD, and 29 controls. ERC, subiculum, cornu ammonis (CA)1, CA2, CA3, and dentate gyrus (DG)&CA4 were traced on T2-weighted images. Analyses of covariance, adjusted for age, sex, and intracranial volume showed that compared with controls and patients with MCI, patients with AD had significantly smaller ERC, subiculum, CA1, CA3, and DG&CA4 volumes. Trend analyses revealed similar associations between ERC and hippocampal subfields and diagnostic group. Older age was significantly associated with smaller CA1 and DG&CA4 volumes. In conclusion, almost all hippocampal subfields and ERC show volume reductions in patients with AD compared with controls and patients with MCI. Future, larger studies should determine which subfields are affected earliest in the disease process and what mechanisms underlie the volume loss.


Asunto(s)
Envejecimiento/patología , Enfermedad de Alzheimer/patología , Región CA1 Hipocampal/patología , Región CA2 Hipocampal/patología , Región CA3 Hipocampal/patología , Disfunción Cognitiva/patología , Giro Dentado/patología , Imagen de Difusión por Resonancia Magnética , Corteza Entorrinal/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Tamaño de los Órganos
18.
J Alzheimers Dis ; 38(1): 211-21, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23948936

RESUMEN

BACKGROUND: Cerebral microbleeds are a manifestation of small vessel disease and are common in patients with Alzheimer's disease (AD). However, their clinical significance in this condition is uncertain. We hypothesized that microbleeds contribute to disturbances of the cerebral network in AD and as such may affect cognition. OBJECTIVE: The goal of this study was to examine the relationship between microbleeds and brain networks in patients with amnestic mild cognitive impairment (aMCI) or early AD. METHODS: Sixty-seven patients (77.9 ± 7.5 years) with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph theoretical analysis were used to reconstruct brain networks and to quantify network efficiency for each patient. Network measures were compared between patients without and with ≥1 microbleeds and between patients without or with ≥3 microbleeds. In secondary analyses, cognitive functioning was compared between groups. Analyses were adjusted for age and gender, and additionally for other markers of small vessel disease and atrophy. RESULTS: Network measures did not differ between patients with ≥1 microbleed (n = 26) and patients without microbleeds (n = 41). However, patients with ≥3 microbleeds (n = 11) showed significant white matter disruptions, longer path length, and less global efficiency than patients without microbleeds, independent of other markers of small vessel disease and atrophy. Cognitive functioning did not differ between patients without microbleeds and patients with ≥1 or ≥3 microbleeds. CONCLUSION: Multiple microbleeds are related to structural network disruption in patients with early AD, but their direct impact on cognitive functioning appears to be limited.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Corteza Cerebral/patología , Hemorragia Cerebral/etiología , Hemorragia Cerebral/patología , Red Nerviosa/patología , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Imagen de Difusión Tensora , Función Ejecutiva , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria , Procesos Mentales , Pruebas Neuropsicológicas , Aprendizaje Verbal
19.
J Alzheimers Dis ; 39(1): 163-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24121967

RESUMEN

Cerebral microinfarcts (CMIs) are a common finding in neuropathological studies of aging and dementia. Recently, it has become possible to detect CMIs in vivo. We studied CMI occurrence in 29 patients with mild cognitive impairment or early Alzheimer's disease (AD) and 22 non-demented individuals on 7Tesla MRI. CMI occurrence in patients (55%) and controls (45%) was not significantly different. In patients, CMI number tended to be related to microbleed number (p = 0.07). This first in vivo study of CMIs in early AD does not confirm findings from autopsy studies. Further studies are needed to clarify the role of CMIs in AD.


Asunto(s)
Enfermedad de Alzheimer/etiología , Infarto Cerebral/complicaciones , Infarto Cerebral/diagnóstico , Disfunción Cognitiva/etiología , Anciano , Enfermedad de Alzheimer/diagnóstico , Autopsia , Trastornos del Conocimiento/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Valores de Referencia
20.
PLoS One ; 8(6): e66610, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23805246

RESUMEN

Cerebral microbleeds are associated with vascular disease and dementia. They can be detected on MRI and receive increasing attention. Visual rating is the current standard for microbleed detection, but is rater dependent, has limited reproducibility, modest sensitivity, and can be time-consuming. The goal of the current study is to present a tool for semi-automated detection of microbleeds that can assist human raters in the rating procedure. The radial symmetry transform is originally a technique to highlight circular-shaped objects in two-dimensional images. In the current study, the three-dimensional radial symmetry transform was adapted to detect spherical microbleeds in a series of 72 patients from our hospital, for whom a ground truth visual rating was made by four raters. Potential microbleeds were automatically identified on T2*-weighted 3.0 T MRI scans and the results were visually checked to identify microbleeds. Final ratings of the radial symmetry transform were compared to human ratings. After implementing and optimizing the radial symmetry transform, the method achieved a high sensitivity, while maintaining a modest number of false positives. Depending on the settings, sensitivities ranged from 65%-84% compared to the ground truth rating. Rating of the processed images required 1-2 minutes per participant, in which 20-96 false positive locations per participant were censored. Sensitivities of individual raters ranged from 39%-86% compared to the ground truth and required 5-10 minutes per participant per rater. The sensitivities that were achieved by the radial symmetry transform are similar to those of individual experienced human raters, demonstrating its feasibility and usefulness for semi-automated microbleed detection.


Asunto(s)
Hemorragia Cerebral/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Sensibilidad y Especificidad
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