Internamiento involuntario vs. Retención ilegal en pacientes contrastorno mental grave / Involuntary internment vs. Illegal retention in patients with serious mental disorder

Aunque una buena actitud hacia la terapia y el cumplimiento de la misma son claves para el éxito del tratamiento, en ciertas situaciones el uso de medidas coercitivas en personas con trastornos mentales es la única forma de prevenir daños graves al paciente y a otras personas. La decisión de utilizar estas medidas, como el internamiento involuntario, es un desafío para los médicos, ya que tienen que lidiar no solo con la voluntad del paciente y de sus familiares, que se encuentran en una situación emocional desbordada, sino también con el conocimiento de la normativa vigente, especialmente complejas. Para proteger los derechos del paciente en estas situaciones difíciles y del personal clínico, es esencial que el mismo conozca los límites de su actuación en el marco del procedimiento legal. Por ello, se necesitan más estudios en la materia, que ofrezcan conclusiones contrastadas con respecto a las diferencias entre el internamiento involuntario y la retención ilegal.(AU)

Even though a good attitude towards therapy and adherence are key to an effective treatment, in certain circumstances the use of coercive actions in people with mental disorders is the only way to prevent serious harm to the patient and to others. The choice to use coercive measures, such as involuntary internment, is a challenge for doctors, since not only do they have to deal with the patient and their relatives who are in a highly emotional situation, but there are also complex legal regulations. To defend the rights of patients in these difficult situations, and to avoid legal consequences for clinical staff due to illegal acts, it is essential that staff are familiar with all of the relevant legal rules and procedures. Further studies are warranted to obtain clear conclusions regarding differences between involuntary internment and illegal retention.(AU)

Brain activity changes with emotional words in different stages of psychosis.

BACKGROUND: To date, a large number of functional magnetic resonance imaging (fMRI) studies have been conducted on psychosis. However, little is known about changes in brain functioning in psychotic patients using an emotional auditory paradigm at different stages of the disease. Such knowledge is important for advancing our understanding of the disorder and thus creating more targeted interventions. This study aimed to investigate whether individuals with first-episode psychosis (FEP) and chronic schizophrenia show abnormal brain responses to emotional auditory processing and to compare the responses between FEP and chronic schizophrenia. METHODS: Patients with FEP (n = 31) or chronic schizophrenia (n = 23) and healthy controls (HCs, n = 31) underwent an fMRI scan while presented with both emotional and nonemotional words. RESULTS: Using HC as a reference, patients with FEP showed decreased right temporal activation, while patients with chronic schizophrenia showed increased bilateral temporal activation. When comparing the patient groups, individuals with FEP showed lower frontal lobe activation. CONCLUSION: To the best of our knowledge, this is the first study with an emotional auditory paradigm used in psychotic patients at different stages of the disease. Our results suggested that the temporal lobe might be a key issue in the physiopathology of psychosis, although abnormal activation could also be derived from a connectivity problem. There is lower activation in the early stage and evolution to greater activation when patients become chronic. This study highlights the relevance of using emotional paradigms to better understand brain activation at different stages of psychosis.

Public stigma profile toward mental disorders across different university degrees in the University of Valencia (Spain).

Background: A large proportion of studies carried out in recent years in different populations have shown that stigma toward mental disorders is highly prevalent. In the present study we conducted a comprehensive assessment of stigma to describe and compare stigma toward mental disorders in students enrolled in five different university degrees. Methods: Three hundred and twenty-five students from the University of Valencia (Spain), attending the second term of their first-degree courses in the faculties of medicine, psychology, teaching, economics, and data science participated in this cross-sectional study. Stigma was measured using: the Reported and Intended Behavior Scale (RIBS), the Scale of Community Attitudes toward Mental Illness (CAMI), the Attribution Questionnaire (AQ-27), and the Knowledge about Mental Illness test (KMI). Results: We found different patterns of stigma according to gender, the fact of knowing or living with a person with mental disorders and the university degree studied. Overall, women show fewer stigmatizing attitudes than men but similar stereotypes and prejudice toward people with mental disorders. However, the pattern of results across degrees is more complex. Overall, students of medicine, psychology and teaching showed fewer stigmatizing attitudes than students of economics and data science but differences between degrees were more subtle in stereotypes and prejudice toward people with mental disorders. Conclusion: Our study suggests the existence of different profiles of stigma in relation to mental disorders in university students. These profiles varied in relation with the degree being studied, gender and already knowing or living with a person with mental disorders.

Precuneus and insular hypoactivation during cognitive processing in first-episode psychosis: Systematic review and meta-analysis of fMRI studies.

INTRODUCTION: The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP. METHODS: Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines. RESULTS: Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum. CONCLUSIONS: While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation.

Neuroimaging correlates of insight in non-affective psychosis: A systematic review and meta-analysis.

OBJECTIVE: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis. METHODS: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI of the 11 studies that were whole-brain and reported maps or peaks of correlation of studies investigating the grey matter volumetric correlates of insight assessments of non-affective psychosis, PubMed and OVID datasets were independently reviewed for articles reporting neuroimaging correlates of insight in non-affective psychosis. Quality assessment was realized following previous methodological approaches for the ABC quality assessment test of imaging studies, based on two main criteria: the statistical power and the multidimensional assessment of insight. Study peaks of correlation between grey matter volume and insight were used to recreate brain correlation maps. RESULTS: A total of 418 records were identified through database searching. Of these records, twenty-three magnetic resonance imaging (MRI) studies that used different insight scales were included. The quality of the evidence was high in 11 studies, moderate in nine, and low in three. Patients with reduced insight showed decreases in the frontal, temporal (specifically in superior temporal gyrus), precuneus, cingulate, insula, and occipital lobes cortical grey matter volume. The meta-analysis indicated a positive correlation between grey matter volume and insight in the right insula (i.e., the smaller the grey matter, the lower the insight). CONCLUSION: Several brain areas might be involved in impaired insight in patients with non-affective psychoses. The methodologies employed, such as the applied insight scales, may have contributed to the considerable discrepancies in the findings.

Precuneus and insular hypoactivation during cognitive processing in first-episode psychosis: Systematic review and meta-analysis of fMRI studies / Hipoactivación precúnea e insular durante el procesamiento cognitivo en el primer episodio psicótico: revisión sistemática y metaanálisis de estudios de fMRI

Introduction: The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP.Methods: Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines.Results: Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum.Conclusions: While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation. (AU)

Introducción:Los correlatos neurales de la disfunción cognitiva en el primer episodio psicótico (PEP) aún no están claros. Esta revisión y este metaanálisis proporcionan una actualización de la localización de las anormalidades en la respuesta cerebral medida por fMRI a los procesos cognitivos en individuos con PEP.Métodos: Revisión sistemática y metaanálisis basado en vóxeles de estudios cros-seccionales de fMRI que comparen respuestas neuronales a tareas cognitivas entre individuos con PEP y controles sanos de acuerdo con las guías PRISMA.Resultados: Se incluyeron 26 estudios, que comprendían 598 individuos con PEP y 567 controles sanos. Los estudios individuales reportaban hipoactivación estadísticamente significativa en la corteza prefrontal dorsolateral (6 estudios), el lóbulo frontal (8 estudios), el cíngulo (6 estudios) y la ínsula (5 estudios). El metaanálisis mostró hipoactivación estadísticamente significativa en la ínsula anterior izquierda, el precúneo y el cuerpo estriado bilateral.Conclusiones: Si bien los estudios tienden a resaltar la hipoactivación frontal durante las tareas cognitivas en PEP, nuestros resultados metaanalíticos muestran que el precúneo izquierdo y la ínsula presentan principalmente una activación aberrante en PEP que puede estar asociada con la atribución de saliencia a estímulos externos y relacionada con déficits en la percepción y la regulación. (AU)

Neuroimaging correlates of insight in non-affective psychosis: A systematic review and meta-analysis / Revisión sistemática y metaanálisis en neuroimagen y conciencia de enfermedad en psicosis no afectivas

Objective: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis.Methods: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI of the 11 studies that were whole-brain and reported maps or peaks of correlation of studies investigating the grey matter volumetric correlates of insight assessments of non-affective psychosis, PubMed and OVID datasets were independently reviewed for articles reporting neuroimaging correlates of insight in non-affective psychosis. Quality assessment was realized following previous methodological approaches for the ABC quality assessment test of imaging studies, based on two main criteria: the statistical power and the multidimensional assessment of insight. Study peaks of correlation between grey matter volume and insight were used to recreate brain correlation maps.Results: A total of 418 records were identified through database searching. Of these records, twenty-three magnetic resonance imaging (MRI) studies that used different insight scales were included. The quality of the evidence was high in 11 studies, moderate in nine, and low in three. Patients with reduced insight showed decreases in the frontal, temporal (specifically in superior temporal gyrus), precuneus, cingulate, insula, and occipital lobes cortical grey matter volume. The meta-analysis indicated a positive correlation between grey matter volume and insight in the right insula (i.e., the smaller the grey matter, the lower the insight). (AU)

Objetivo: Los correlatos neurológicos de la conciencia de enfermedad en psicosis no afectivas siguen sin estar claros. Este estudio tiene como objetivo revisar y metaanalizar los estudios que evalúan los correlatos volumétricos de la materia gris de la conciencia de enfermedad deficiente en la psicosis no afectiva.Métodos: Este estudio consistió en una revisión sistemática de 23 estudios y un metaanálisis con SDM-PSI de los 11 estudios que examinaron todo el cerebro y reportaron mapas o picos de correlación de estudios que investigan los correlatos volumétricos de materia gris de evaluaciones de insight de psicosis no afectiva. Los conjuntos de datos de PubMed y OVID se revisaron de forma independiente para los artículos que informaban sobre correlaciones de neuroimagen de insight en psicosis no afectiva. La evaluación de la calidad de los estudios de imagen se realizó siguiendo enfoques metodológicos previos usando la prueba de evaluación de la calidad ABC basados en dos criterios principales: el poder estadístico y la evaluación multidimensional del insight. Los picos de correlación del estudio entre el volumen de materia gris y la conciencia de enfermedad fueron utilizados para recrear mapas de correlación cerebral.Resultados: Se incluyeron veintitrés estudios de imágenes por resonancia magnética (IRM) que utilizaron diferentes escalas de conciencia de enfermedad. La calidad de los estudios revisados fue clasificada como alta en 11 estudios, moderada en 9 estudios y baja en 3 estudios. Los pacientes con insight reducido mostraron disminuciones en el volumen de materia gris cortical de los lóbulos frontal, temporal (específicamente en la circunvolución temporal superior), precúneo, cingulado, ínsula y lóbulo occipital. El metaanálisis mostró una correlación positiva entre el volumen de materia gris y la conciencia de enfermedad en la ínsula derecha (es decir, cuanto más pequeña es la materia gris, menor es el insight). (AU)

The Impact of the COVID-19 Pandemic on the Lifestyles and Levels of Anxiety and Depression of Patients with Schizophrenia: A Retrospective Observational Study.

The movement restrictions put in place as a result of the COVID-19 pandemic required modification of the population's usual routines, including those of the most vulnerable groups such as patients with schizophrenia. This was a retrospective observational study. We used an online survey to collect information on patient adherence to the Mediterranean diet (Mediterranean Diet Adherence Screener questionnaire), physical exercise (International Physical Activity Questionnaire Short Form), and tobacco consumption and levels of anxiety and depression (Hospital Anxiety and Depression Scale) before and during the movement restrictions. A total of 102 people with schizophrenia participated in this study. During the COVID-19 pandemic lockdown the participants significantly increased the number of minutes spent sitting per day (z = -6.73; p < 0.001), decreased the time they spent walking (z = -6.32; p < 0.001), and increased their tobacco consumption (X2 = 156.90; p < 0.001). These results were also accompanied by a significant increase in their reported levels of anxiety (z = -7.45; p < 0.001) and depression (z = -7.03, p < 0.001). No significant differences in patient diets during the pandemic compared to before the movement restrictions were reported. These results suggest the need to implement specific programs to improve lifestyle and reduce anxiety and depression during possible future pandemic situations.

Study Protocol-Coping With the Pandemics: What Works Best to Reduce Anxiety and Depressive Symptoms.

Background: The coronavirus disease 2019 (COVID-19) pandemic and lockdown might increase anxiety and depressive symptoms in most individuals. Health bodies recommend several coping behaviors to protect against such symptoms, but evidence on the relationship between these behaviors and symptoms mostly comes from cross-sectional studies in convenience samples. We will conduct a prospective longitudinal study of the associations between coping behaviors and subsequent anxiety and depressive symptoms during the COVID-19 pandemic in a representative sample of the Spanish general adult population. Methods: We will recruit 1,000 adult participants from all autonomous communities of Spain and with sex, age, and urbanicity distributions similar to those of their populations and assess anxiety and depressive symptoms and coping behaviors using fortnightly questionnaires and real-time methods (ecological momentary assessments) for 1 year. The fortnightly questionnaires will inquire about anxiety and depressive symptoms [General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)] and the frequency of 10 potential coping behaviors (e.g., follow a routine) during the past 2 weeks. In addition, we will collect several variables that could confound or moderate these associations. These will include subjective well-being [International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) and Satisfaction with Life Scale (SWLS)], obsessive-compulsive symptoms [Obsessive Compulsive Inventory-Revised (OCI-R)], personality and emotional intelligence [International Personality Item Pool (IPIP) and Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF)], sociodemographic factors (e.g., work status, housing-built environment), and COVID-19 pandemic-related variables (e.g., hospitalizations or limitations in social gatherings). Finally, to analyze the primary relationship between coping behaviors and subsequent anxiety and depressive symptoms, we will use autoregressive moving average (ARMA) models. Discussion: Based on the study results, we will develop evidence-based, clear, and specific recommendations on coping behaviors during the COVID-19 pandemic and lockdown. Such suggestions might eventually help health bodies or individuals to manage current or future pandemics.

Neuroimaging correlates of insight in non-affective psychosis: A systematic review and meta-analysis.

OBJECTIVE: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis. METHODS: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI of the 11 studies that were whole-brain and reported maps or peaks of correlation of studies investigating the grey matter volumetric correlates of insight assessments of non-affective psychosis, PubMed and OVID datasets were independently reviewed for articles reporting neuroimaging correlates of insight in non-affective psychosis. Quality assessment was realized following previous methodological approaches for the ABC quality assessment test of imaging studies, based on two main criteria: the statistical power and the multidimensional assessment of insight. Study peaks of correlation between grey matter volume and insight were used to recreate brain correlation maps. RESULTS: A total of 418 records were identified through database searching. Of these records, twenty-three magnetic resonance imaging (MRI) studies that used different insight scales were included. The quality of the evidence was high in 11 studies, moderate in nine, and low in three. Patients with reduced insight showed decreases in the frontal, temporal (specifically in superior temporal gyrus), precuneus, cingulate, insula, and occipital lobes cortical grey matter volume. The meta-analysis indicated a positive correlation between grey matter volume and insight in the right insula (i.e., the smaller the grey matter, the lower the insight). CONCLUSION: Several brain areas might be involved in impaired insight in patients with non-affective psychoses. The methodologies employed, such as the applied insight scales, may have contributed to the considerable discrepancies in the findings.

Unravelling cases of clozapine-related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients reported otherwise: A systematic review.

BACKGROUND: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug-induced hypersensitivity reaction. AIMS: Aim was to review reports of clozapine-related reactions fulfilling the registry of severe cutaneous adverse reaction (RegiSCAR) criteria for DRESS syndrome reported as such or otherwise, to provide a descriptive overview of demographic patterns, clinical manifestations, and DRESS course and investigate associations between demographic, DRESS parameters, and clinical outcomes. METHODS: This review was conducted following preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (registration number CRD42020156385). We searched PubMed/Embase/PsychInfo/Cochrane for reports of clozapine-related reactions meeting RegiSCAR criteria. Associations between RegiSCAR scores and time-to-recovery with demographic/clinical variables were assessed. Demographic/clinical characteristics of patients with versus without reported DRESS were compared using non-parametrical tests. RESULTS: We identified 26 reports of 27 patients meeting RegiSCAR criteria. Males (n = 19, 70.4%) and patients with schizophrenia (n = 18, 66.7%) were mainly affected. Twelve patients (44.4%) received clozapine-monotherapy. DRESS symptoms manifested within a month after clozapine initiation (n = 24, 88.9%). Lungs and liver were the most common organs involved (n = 12, 44.4%; n = 11, 40.7%), with a mean time to recovery of 33.75 days. Clozapine rechallenge led to DRESS recurrence in four patients. Death rate was 7.4%. No associations were detected between RegiSCAR criteria or days to recovery with any demographic/clinical variables. No differences between patients with versus without reported DRESS were detected. CONCLUSIONS: Clozapine-related DRESS may be rare, but also underreported. Clinicians need to be aware of it even in patients under clozapine-monotherapy or without skin rash.

Precuneus and insular hypoactivation during cognitive processing in first-episode psychosis: Systematic review and meta-analysis of fMRI studies.

INTRODUCTION: The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP. METHODS: Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines. RESULTS: Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum. CONCLUSIONS: While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation.

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a systematic review.

INTRODUCTION: The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe, multiorganic, and potentially life-threatening drug-induced hypersensitivity reaction, linked to several common drugs, including antiepileptics, antibiotics, and several psychotropic drugs, including clozapine. Due to the importance of clozapine in the management of treatment-resistant schizophrenia, a systematic review and characterization of clozapine-related DRESS syndrome is long overdue. AREAS COVERED: This systematic review was conducted following PRISMA guidelines. PubMed, Embase, PsychINFO, and the Cochrane Library databases were independently reviewed up to 1 November 2019 for articles reporting clozapine-related DRESS syndrome cases. The RegiSCAR score system was applied to systematically characterize the clinical presentations of selected studies. EXPERT OPINION: Clozapine-related DRESS syndrome was reported in six patients from four articles. Five patients received polypharmacy. Skin rash and liver involvement with elevated liver enzymes were very common. No fatal cases were found. Treatment mainly included clozapine discontinuation and immunosuppression. The mismatch between incidences of DRESS with other responsible drugs, the common misdiagnosis of this syndrome, and the fact that an extensive literature search only identified six cases suggests that clozapine-related DRESS may be overlooked. It is, therefore, necessary to optimize diagnostic strategies to identify immune-related side effects of clozapine.

First-Episode Psychotic Patients Showed Longitudinal Brain Changes Using fMRI With an Emotional Auditory Paradigm.

Most previous longitudinal studies of functional magnetic resonance imaging (fMRI) in first-episode psychosis (FEP) using cognitive paradigm task found an increased activation after antipsychotic medications. We designed an emotional auditory paradigm to explore brain activation during emotional and nonemotional word processing. This study aimed to analyze if longitudinal changes in brain fMRI BOLD activation is present in patients vs. healthy controls. A group of FEP patients (n = 34) received clinical assessment and had a fMRI scan at baseline and follow-up (average, 25-month interval). During the fMRI scan, both emotional and nonemotional words were presented as a block design. Results were compared with a pair of healthy control group (n = 13). Patients showed a decreased activation at follow-up fMRI in amygdala (F = 4.69; p = 0.04) and hippocampus (F = 5.03; p = 0.03) compared with controls. Middle frontal gyrus was the only area that showed a substantial increased activation in patients (F = 4.53; p = 0.04). A great heterogeneity in individual activation patterns was also found. These results support the relevance of the type of paradigm in neuroimaging for psychosis. This is, as far as we know, the first longitudinal study with an emotional auditory paradigm in FEP. Our results suggested that the amygdala and hippocampus play a key role in psychotic disease. More studies are needed to understand the heterogeneity of response at individual level.

Longitudinal studies of functional magnetic resonance imaging in first-episode psychosis: A systematic review.

BACKGROUND: Little is known about changes in brain functioning after first-episode psychosis (FEP). Such knowledge is important for predicting the course of disease and adapting interventions. Functional magnetic resonance imaging has become a promising tool for exploring brain function at the time of symptom onset and at follow-up. METHOD: A systematic review of longitudinal fMRI studies with FEP patients according to PRISMA guidelines. Resting-state and task-activated studies were considered together. RESULTS: Eleven studies were included. These reported on a total of 236 FEP patients were evaluated by two fMRI scans and clinical assessments. Five studies found hypoactivation at baseline in prefrontal cortex areas, two studies found hypoactivation in the amygdala and hippocampus, and three others found hypoactivation in the basal ganglia. Other hypoactivated areas were the anterior cingulate cortex, thalamus and posterior cingulate cortex. Ten out of eleven studies reported (partial) normalization by increased activation after antipsychotic treatment. A minority of studies observed hyperactivation at baseline. CONCLUSIONS: This review of longitudinal FEP samples studies reveals a pattern of predominantly hypoactivation in several brain areas at baseline that may normalize to a certain extent after treatment. The results should be interpreted with caution given the small number of studies and their methodological and clinical heterogeneity.