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2.
Psychiatry Res Neuroimaging ; 305: 111196, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33010582

RESUMO

Gender differences in mood and anxiety disorders are well-established. However, the neural basis of these differences is not clear yet, especially in terms of brain metabolism. Indeed, although several proton Magnetic Resonance Spectroscopy (¹H MRS) investigations reported different metabolic levels in both depression and anxiety disorders, which have been also linked to symptoms severity and response to treatment, the role of gender on these differences have not been explored yet. Therefore, this study aims at investigating the role of sex in neurometabolic alterations associated with both mood and anxiety disorders. A 3T single-voxel ¹H MRS acquisition of the dorsolateral prefrontal cortex was acquired from 14 Major Depressive Disorder, 10 Generalized Anxiety Disorder (GAD), 11 Panic Disorder (PD), patients and 16 healthy controls (HC). Among males, PD patients showed significantly lower GPC+PC (also observed in GAD+PD) and Glu levels compared to HC. Finally, a significant group x sex interaction effect was observed in the GPC+PC and Glu levels. We proved the presence of an association between sex and brain metabolites in anxiety spectrum.

3.
Hum Brain Mapp ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073925

RESUMO

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33027802

RESUMO

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.

5.
J Vis Exp ; (162)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32894263

RESUMO

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

6.
Epidemiol Psychiatr Sci ; 29: e166, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32895076

RESUMO

Since its discovery in 1997, the default mode network (DMN) and its components have been extensively studied in both healthy individuals and psychiatric patients. Several studies have investigated possible DMN alterations in specific mental conditions such as bipolar disorder (BD). In this review, we describe current evidence from resting-state functional magnetic resonance imaging studies with the aim to understand possible changes in the functioning of the DMN in BD. Overall, several types of analyses including seed-based and independent component have been conducted on heterogeneous groups of patients highlighting different results. Despite the differences, findings seem to indicate that BD is associated with alterations in both frontal and posterior DMN structures, mainly in the prefrontal, posterior cingulate and inferior parietal cortices. We conclude this review by suggesting possible future research directions.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Vias Neurais/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Humanos
7.
J Affect Disord ; 277: 671-680, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911217

RESUMO

BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS). METHODS: During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference. RESULTS: The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions. LIMITATIONS: Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too. CONCLUSIONS: Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas.

8.
J Affect Disord ; 278: 209-217, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32971313

RESUMO

BACKGROUND: Although many studies found an association between psychiatric disorders, especially major depressive disorder, and vitamin D deficiency, little is still known about the association between vitamin D and bipolar disorder (BD). Therefore, the present review aims at providing an overview of the available literature exploring the role of vitamin D in BD patients in different phases of the disease. METHODS: From a bibliographic research in PubMed until April 2020, we collected ten original studies that fulfilled our inclusion criteria. RESULTS: No significant differences in vitamin D levels between BD patients and other psychiatric disorders were found by most of the studies. In the majority of the studies, the average values of vitamin D in BD population were sub-threshold for vitamin D deficiency. Moreover, although an association between vitamin D levels and clinical symptomatology was observed in BD patients, it cannot be considered a specific marker of this disorder but a common characteristic shared with other psychiatric disorders, including schizophrenia and major depressive disorder. Finally, vitamin D supplementation was associated with a reduction in both depressive and manic symptoms. LIMITATIONS: Few studies with small and heterogeneous populations. Methodological heterogeneity in terms of vitamin D measurement and threshold. CONCLUSIONS: The results showed that vitamin D status does not differ between BD and other psychiatric conditions. However, given the correlation between vitamin D levels and depressive or manic symptoms, we could hypothesize that an adequate vitamin D status could positively affect the mood balance thanks to its immunomodulatory activity.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32994122

RESUMO

BACKGROUND AND AIM: Heterogeneous results have been obtained in the relationship between Uric Acid (UA) and Target Organ Damage (TOD). In the present study we sought to assess the prevalence of hyperuricemia in healthy subjects as well as the role of UA in determining TOD. We evaluated vascular, cardiac and renal TODs in the whole population as well as sub-grouped by gender. METHODS AND RESULTS: As many as 379 blood donors participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT). Hyperuricemia was defined with the classic cut-off (>7.0 in men and >6.0 mg/dL in women) but also with a most recently defined one (5.6 mg/dL for both sex). Hyperuricemia was present in 6.3% of the whole population (7.3% males, 2.8% females) considering the classic cut-off, while, with the recently identified one, it was present in 28.2% of the whole population (37.3% males, 4.7% females). Despite all the evaluated TODs significantly correlated with UA, linear multivariate regression analysis showed that none of them, except for GFR, displayed UA as a significant covariate. Similar figures were found also when both correlation and linear regression analyses were repeated in the two genders separately. CONCLUSIONS: Hyperuricemia is an important problem also in healthy subjects and its prevalence could further increase if lower cut-off will be used. In this specific population UA is significantly associated with renal impairment while this was not the case for cardiac and vascular damage.

10.
Biol Psychiatry ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32782139

RESUMO

BACKGROUND: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. METHODS: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. RESULTS: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. CONCLUSIONS: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research.

11.
Redox Biol ; 36: 101682, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32810737

RESUMO

There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity. Interestingly, physiological serum levels of 27-hydroxycholesterol in SARS-CoV-2 positive subjects were significantly decreased compared to the matched control group, reaching a marked 50% reduction in severe COVID-19 cases. Moreover, no correlation at all was observed between 24-hydroxycholesterol and 25-hydroxycholesterol serum levels and the severity of the disease. Opposite to that of 27-hydroxycholesterol was the behaviour of two recognized markers of redox imbalance, i.e. 7-ketocholesterol and 7ß-hydroxycholesterol, whose serum levels were significantly increased especially in severe COVID-19. The exogenous administration of 27-hydroxycholesterol may represent in the near future a valid antiviral strategy in the worsening of diseases caused by present and emerging coronaviruses.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/sangue , Hidroxicolesteróis/sangue , Pneumonia Viral/sangue , Idoso , Animais , Biomarcadores/sangue , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Feminino , Células Hep G2 , Humanos , Hidroxicolesteróis/farmacologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Células Vero
12.
J Affect Disord ; 276: 1046-1051, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763589

RESUMO

BACKGROUND: Affective psychosis is a common mental disorder characterized by structural/functional brain abnormalities, which seem to occur also at the early stages of the disease. However, the role of psychotropic medications on brain structure and function in affective first episode psychosis (A-FEP) still remains uncertain. Therefore, with this review we aim to gain more robust understanding regarding the potential effect of pharmacological treatments on the brain in A-FEP patients also experiencing a first manic episode. METHODS: A search on PuBMed and Web of Science of longitudinal structural and functional Magnetic Resonance Imaging (MRI) as well as Diffusion Tensor Imaging (DTI) studies, exploring the effect of medications on the brain in A-FEP, was conducted. We selected nine studies, three randomized or pseudo-randomized controlled trials and six observational studies. RESULTS: Overall the studies showed that a) mood stabilizers (MS) have no effect on gray matter (GM) volumes and a protective role on white matter (WM) volumes, b) antipsychotics (AP) have an unclear effect on GM volumes and a less potent effect on WM volumes compared to MS and c) both MS and AP tend to normalize brain activation and connectivity. LIMITATIONS: The small sample size, the observational design of the majority of the studies and the different methodological approaches limit the conclusion of this review. CONCLUSIONS: Medications seem to have a minor role on structural changes occurring in A-FEP patients during the early stages of the disease, while their effect on brain activation and connectivity seems more pronounced, but far to be conclusive.

13.
J Affect Disord ; 276: 1095-1101, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777647

RESUMO

BACKGROUND: Deficits in the ability to think about own mental states and that of others (mindreading) are seen as key aspects of borderline personality disorder (BPD), which could sustain BPD symptoms. Interestingly, some studies showed that in BPD patients metacognition is selectively compromised and could improve during treatments. However, empirical findings are inconsistent, and it is debatable whether BPD presents a specific profile of mindreading impairments that could improve during treatments. METHODS: We performed a bibliographic research on PubMed , Google Scholar and Scopus of all studies investigating a) the metacognitive functioning in the BPD patients and b) the link between psychotherapy, metacognition improvement and BPD symptomatology. A total of 11 studies met our inclusion criteria and considered metacognition following the definition proposed by Semerari. RESULTS: Overall, the results suggest that BPD metacognitive profile mainly includes difficulties in metacognitive sub-domains of integration, differentiation and mastery. The type of treatment most appropriate to improve metacognitive abilities and reduce symptoms seemed to be a long term treatment and specifically focused on metacognitive deficits. LIMITATIONS: Lack of a control group, small sample sizes and heterogeneity in terms of gender, age, comorbidities and other ongoing treatments are the key limits of the original studies reviewed. CONCLUSIONS: The results sustain the hypothesis of a selective and specific metacognitive impairment in BPD patients that could improve during treatments together with their symptomatology. However, more studies are needed to further investigate the role of metacognition in the effectiveness of treatments.

14.
J Affect Disord ; 276: 1109-1118, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777649

RESUMO

BACKGROUND: Most recent evidence support a rapid and sustained antidepressant effect of subanesthetic dose of intravenous ketamine in patients with major depressive disorder (MDD). However, clinical and animal studies investigating the effects of intravenous ketamine on specific functional domains disrupted by depression reported conflicting results. Therefore, the aim of this review is to provide an overview of the recent findings exploring the cognitive effects of ketamine in depression. METHODS: After a bibliographic search on PubMed, Medline and PsycInfo, we retrieved 11 original studies meeting our research criteria, 7 in humans with MDD or Treatment Resistant Disorder and 4 using rats models for depression. RESULTS: Overall the results showed that a) ketamine reduced activation and normalized connectivity measures of several brain regions related to depressive behaviors and reversed deficits in cognitive flexibility and coping response strategy in rats with depressive features, and b) ketamine leads to a no significant impairment on neurocognitive functions in most of the studies, with only three studies observing improvements in speed of processing, verbal learning, sustained attention and response control, verbal and working memory. LIMITATIONS: The methodological heterogeneity, in terms of neuropsychological tests used and cognitive domain explored, of the studies included. CONCLUSIONS: Most of the studies included showed no significant cognitive impairments in MDD patients after ketamine treatment. Furthermore, the results of the fMRI studies considered suggest that ketamine may have a normalizing effect on brain functions during attentional and emotional processing in MDD patients. However, further studies are needed to confirm these preliminary evidences.

15.
J Affect Disord ; 277: 169-174, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829192

RESUMO

BACKGROUND: Personality disorders (PDs) are severe mental illnesses, characterized by inflexible and enduring response patterns in a broad range of personal and social situations. With the aim of identifying effective and evidence-based interventions, in the last decades we observed a flourishing of the so-called "thirdwave" cognitive-behavioural therapies, where mindfulness appears as relevant factor in promoting individual well-being and treatment response. In this regard, several authors tried to develop new instruments that enable to measure mindfulness skills, such as the Kentucky Inventory of Mindfulness Skills (KIMS), the Five Facet Mindfulness Questionnaire (FFMQ) and the Philadelphia Mindfulness Scale (PHLMS). The aim of this review is to provide new insights about the mindfulness questionnaires currently used in longitudinal studies in PDs by providing a benchmark for future studies evaluating mindfulness changes associated to therapeutic interventions. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search in PubMed was performed. Three reviewers conducted the data extraction. Longitudinal studies on PDs evaluating mindfulness skills through a validated questionnaire were selected. Ten studies met the selection criteria. RESULTS: The majority of the studies reviewed (N=7) detected an increase in mindfulness skills (4 rated with FFMQ, 2 KIMS, and 1 Philadelphia Mindfulness Scale). Finally, from the selected studies mindfulness changes were also associated with clinical amelioration. LIMITATIONS: Few studies evaluate male patients and PDs other than borderline personality disorder. CONCLUSION: Although mindfulness is a complex construct to operationalize, the considered questionnaires emerged as useful instruments for clinicians to detect changes in mindfulness abilities. In particular, currently the FFMQ appears as the most suitable measure.

16.
Redox Biol ; 36: 101682, 2020 09.
Artigo em Inglês | MEDLINE | ID: covidwho-704017

RESUMO

There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity. Interestingly, physiological serum levels of 27-hydroxycholesterol in SARS-CoV-2 positive subjects were significantly decreased compared to the matched control group, reaching a marked 50% reduction in severe COVID-19 cases. Moreover, no correlation at all was observed between 24-hydroxycholesterol and 25-hydroxycholesterol serum levels and the severity of the disease. Opposite to that of 27-hydroxycholesterol was the behaviour of two recognized markers of redox imbalance, i.e. 7-ketocholesterol and 7ß-hydroxycholesterol, whose serum levels were significantly increased especially in severe COVID-19. The exogenous administration of 27-hydroxycholesterol may represent in the near future a valid antiviral strategy in the worsening of diseases caused by present and emerging coronaviruses.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/sangue , Hidroxicolesteróis/sangue , Pneumonia Viral/sangue , Idoso , Animais , Biomarcadores/sangue , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Feminino , Células Hep G2 , Humanos , Hidroxicolesteróis/farmacologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Células Vero
18.
Hum Brain Mapp ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32725849

RESUMO

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

20.
BMC Psychiatry ; 20(1): 377, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680486

RESUMO

BACKGROUND: Increasing evidence suggests a complex role of family influences, such as the exposure to parent psychopathology through parenting behavior, in parent-to-child psychopathology transmission. Parenting behaviour could represent a relevant target of psychoeducative intervention. Given these premises, we aimed to evaluate homotypic and heterotypic relationships between parent and child psychopathology, mediated by parenting behaviours, taking into account the constructs of parent and offspring internalizing and externalizing psychopathology. METHODS: Internalizing and externalizing symptoms in 272 clinically-referred subjects (mean age = 14.5 ± 2.3; F = 23.5%) and their parents (mothers n = 272, fathers n = 242) were assessed through the Child Behavior Checklist and the Adult Self Report; four areas of parenting behaviours were investigated through the Family Life Questionnaire. Multiple mediation models were built, considering mother and father psychopathology scales as independent variables, parenting measures and family functioning as mediators (Affirmation, Rules, Discipline and Special Allowances), child psychopathology scales as dependent variables and demographic variables as covariates. RESULTS: Regression models showed a significant effect of maternal internalizing symptomatology on child externalizing behavioral problems; high levels of maternal pathology predicted high levels of children's psychopathology. A total mediating effect of parenting measures was found: high levels of internalizing symptoms in mothers predicted low levels of affirmation, which in turn predicted high levels of externalizing psychopathology in children. CONCLUSIONS: Our study results confirmed the existence of interdependent links between mothers' psychiatric symptomatology, parenting behaviour and offspring outcomes, specifically in an Italian context. On a clinical and rehabilitation basis, this work offers suggestions about parenting practices, specifically maternal, involved in the maintenance of child psychopathology.

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