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PURPOSE: Child maltreatment (CM) is associated with psychosis; however little is known about the frequency, type, and timing of abuse in the personality pathology domain of psychoticism (PSY) in the DSM-5. The purpose of this study was to analyze childhood trauma typology and frequency according to gender and to identify sensitive periods of susceptibility to CM in women with high PSY. METHODS: The Maltreatment and Abuse Chronology Exposure (MACE) scale was used to evaluate the frequency, severity and timing of each type of maltreatment. The full sample consisted of 83 participants with different psychiatric diagnoses. Psychoticism was assessed with the DSM-5 Personality Inventory (PID-5). To identify the differences in CM exposure between the PSY+ (high psychoticism) and PSY- (low psychoticism) groups, the Mann-Whitney U test, the chi square test and random forest (RF) test were used. RESULTS: Comparing PSY + and PSY-, revealed gender differences in the impact of abuse, with highly frequent and severe types of abuse, in women. In women, PSY + and PSY-, were differentiated especially in non-verbal emotional abuse, peer physical bullying and parental verbal abuse. Several periods with a major peak at age seven followed by peaks at age 17 and 12 years old were identified. CONCLUSION: Increased exposure to CM occurs in women with PSY+. A sensitivity to CM exposure during early childhood and late adolescence could be a risk factor for psychoticism in women.
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Cholesterol and the immune system are involved in Alzheimer's Disease (AD). To investigate the relations among them, we compared the cholesterol content in peripheral blood mononuclear cells (PBMC) of cognitively healthy controls and patients with mild cognitive impairment (MCI) and AD in two independent samples. Free cholesterol content of PBMC was lower in MCI and AD patients, and was modulated by APOE genotype. A decrease of CD8+ and an increase of CD16+ was also found in AD patients. These results suggest that cholesterol levels in PBMCs may represent an early signature of the disease and support the involvement of immune system in AD.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/genética , Leucócitos Mononucleares , Colesterol , BiomarcadoresRESUMO
Objetivo: evaluar la asociación de los síntomas psicopatológicos y el funcionamiento cognitivo con las medidas de calidad de vida subjetiva en pacientes con diagnósticos del espectro de la esquizofrenia. Metodología: se incluyeron 102 pacientes ambulatorios que cumplían criterios DSM-IV-TR para el diagnóstico de alguno de los trastornos del espectro de la esquizofrenia. Los datos se obtuvieron utilizando el Cuestionario Sevilla de Calidad de Vida, la Escala para el síndrome positivo y negativo de la esquizofrenia (PANSS), el Inventario de depresión de Beck y el Inventario de Ansiedad estado/rasgo. Resultados: el análisis de regresión múltiple mostró que los aspectos favorables de la calidad de vida están afectados por la desorganización cognitiva, los síntomas positivos, depresivos y ansiosos. Por otra parte, la presencia de síntomas de carácter emocional está fuertemente asociada a los aspectos desfavorables, lo que hace pensar que esta dimensión sintomática deteriora la percepción subjetiva de bienestar de los pacientes con trastornos del espectro de la esquizofrenia. Conclusiones: los síntomas psicopatológicos y la función cognitiva afectan la calidad de vida subjetiva en pacientes con esquizofrenia. Si el objetivo con el tratamiento es lograr que mejore la calidad de vida percibida, las estrategias deben considerar la búsqueda de la mejoría de los síntomas de carácter emocional, como la depresión, la ansiedad y el malestar emocional.
Objective: To evaluate the association of psychopathological symptoms and cognitive functioning with the measures of subjective quality of life of a group of patients diagnosed with the schizophrenia spectrum. Methodology: The study included 102 outpatients who met the DSM-IV-TR criteria for the diagnosis of schizophrenia spectrum disorders. The data were obtained by means of the Seville Questionnaire of Quality of Life (CSCV), the scale for the positive and negative schizophrenia syndrome (PANSS), the Beck Depression Inventory (BDI) as well as the state-trait Anxiety Inventory (STAI). Results: The multiple regression analysis showed, on one hand, that favorable aspects of quality of life are affected by cognitive disorganization, positive, depressive and anxiety symptoms. On the other hand, the presence of emotional symptoms is strongly associated with unfavorable aspects, which suggests that this symptomatic dimension impairs the subjective perception of well-being of patients with schizophrenia spectrum disorders. Conclusions: Psychopathological symptoms and cognitive function affect the subjective quality of life in patients with schizophrenia. If the aim of the treatment is to improve the perceived quality of life, the strategies should consider seeking the improvement symptoms of an emotional nature, such as depression / anxiety and emotional distress.
Objetivo: avaliar a associação dos sintomas psicopatológicos e o funcionamento cognitivo com as medidas de qualidade de vida subjetiva em pacientes com diagnósticos do espectro da esquizofrenia. Metodologia: se incluíram 102 pacientes ambulatórios que cumpriam critérios DSMIV-TR para o diagnóstico de algum dos transtornos do espectro da esquizofrenia. Os dados se obtiveram utilizando o Questionário Sevilla de Qualidade de Vida, a Escala para a síndrome positiva e negativa da esquizofrenia (PANSS), o Inventário de depressão de Beck e o Inventário de Ansiedade estado/característica. Resultados: a análise de regressão múltipla mostrou que os aspectos favoráveis da qualidade de vida estão afetados pela desorganização cognitiva, os sintomas positivos, depressivos e ansiosos. Por outra parte, a presença de sintomas de carácter emocional está fortemente associada aos aspectos desfavoráveis, o que se faz pensar que esta dimensão sintomática deteriora a percepção subjetiva de bem-estar dos pacientes com transtornos do espectro da esquizofrenia. Conclusões: os sintomas psicopatológicos e a função cognitiva afetam a qualidade de vida subjetiva em pacientes com esquizofrenia. Se o objetivo com o tratamento é conseguir que melhore a qualidade de vida percebida, as estratégias devem considerar a busca da melhoria dos sintomas de carácter emocional, como a depressão, a ansiedade e o mal-estar emocional.
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Humanos , Esquizofrenia , Qualidade de Vida , CogniçãoRESUMO
Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.
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Depressão Pós-Parto/epidemiologia , Depressão/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Personalidade , Ideação Suicida , Adulto , Estudos de Coortes , Feminino , Humanos , Mães/psicologia , Neuroticismo , Período Pós-Parto/psicologia , Escalas de Graduação Psiquiátrica , Fatores de Risco , Apoio Social , Espanha , Inquéritos e QuestionáriosRESUMO
Destruction of the myelin sheath in the central nervous system (CNS) is prominent in many clinico-pathologic conditions. Among animal models that reproduce the pathological features of de- and remyelination processes, the mouse model of cuprizone administration is widely used. Both hyperactivity and motor impairment have been reported upon cuprizone exposure. The aim of the present study was to assess behaviour in mice after CPZ withdrawal.To summarize, animals showed hypo-activity and deficits in motor coordination when they were subjected to acute demyelinating insult while minor exploratory activity, impairment in motor coordination and lower anxiety levels emerged when remyelination was reached following cuprizone withdrawal. A recovery period of 6 weeks after removal of CPZ was not accompanied by a similar return of normal activity indicating long lasting behavioural effects caused by this neurotoxicant. Specifically, the recovery group showed impairments in neurological functions involved in sensorimotor, neuromuscular, motor coordination and the capacity to cope with a stress-inducing event.
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Comportamento Animal/efeitos dos fármacos , Cuprizona/efeitos adversos , Cuprizona/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Doenças Desmielinizantes/metabolismo , Modelos Animais de Doenças , Asseio Animal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Destreza Motora/efeitos dos fármacos , Bainha de Mielina/patologia , Oligodendroglia/efeitos dos fármacosRESUMO
BACKGROUND: There is a lack of studies investigating the dose-response effect of childhood trauma, recent events and cannabis use on recent psychosis. This study aims to determine the relationship between the level of exposure to stress factors and cannabis use with psychosis and to determine the combination effect among these factors in predicting a psychotic disorder. METHODS: 146 recent onset psychotic (ROP) patients and 61 healthy controls were included. Childhood trauma was evaluated using the childhood trauma questionnaire (CTQ) and recent events using the Holmes-Rahe social readjustment scale. The pattern of cannabis use was assessed by a detailed interview. A hierarchical multiple regression was run in order to determine both the cumulative and independent contribution of each factor in predicting a psychotic disorder. RESULTS: The highest levels of exposure to childhood trauma and cannabis were associated with psychosis while neither low nor high recent event exposure was associated. The combined effect of risk factors yielded a significant association with psychosis (×2â¯=â¯86.76, pâ¯<â¯.001) explaining the 49% of its variation. ROP were more likely to be exposed to one, two or three environmental factors than HC. Exposed to two or all factors were 7.5-fold and 26.7-fold more likely to have a diagnosis of psychosis, respectively. CONCLUSIONS: Our study provides evidence for a cumulative and a dose-response effect of environmental factors on recent psychosis. Considering that cannabis use and stress are highly prevalent in the population with psychosis, investigations of their relationships are needed to implement targeted prevention and treatment strategies.
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Sobreviventes Adultos de Maus-Tratos Infantis , Uso da Maconha/epidemiologia , Transtornos Psicóticos/epidemiologia , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Cannabis , Estudos Transversais , Feminino , Humanos , Masculino , Abuso de Maconha/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Self-injurious behaviour (SIB) is a prevalent form of challenging behaviour in people with intellectual developmental disorders (IDD). Existing research has yielded conflicting findings concerning the major risk factors involved, and in addition, SIB shows multiple topographies and presentations. Although presence of autism spectrum disorders (ASD) and severity of intellectual disability (ID) are known risk factors for SIB, there are no studies comparing SIB topographies by severity degrees of ID and ASD. The purpose of the present paper has been to identify risk factors and topographies for SIB in a representative, stratified and randomised sample of adults with IDD. METHOD: This study was conducted on the basis of data collected by the POMONA-ESP project, in a sample of 833 adults with IDD. Data concerning demographic and health information, ASD symptoms, psychopathology and ID, have been analysed to determine the presence of risk factors for SIB among participants and to explore the occurrence and topographies of SIB across different severity levels of ID and ASD symptoms. RESULTS: Self-injurious behaviour prevalence in the sample was 16.2%. Younger age, oral pain, greater severity of ID, presence of dual diagnosis, psychiatric medication intake and higher scores on Childhood Autism Rating Scale were risk factors for SIB among participants, whereas number of areas with functioning limitations, place of residence, diagnosis of epilepsy and sex were not. SIB was more frequent in participants with ASD symptoms regardless of its severity level, and they displayed a higher number of different topographies of SIB. People with profound ID without co-morbid ASD symptoms showed similar results concerning SIB prevalence and topographies. CONCLUSIONS: Knowledge on risk factors and topographies of SIB might play a vital role in the development of prevention strategies and management of SIB in people with IDD. The mere presence of ASD symptoms, regardless of its severity level, can be a crucial factor to be taken into account in assessing SIB. Accordingly, the presence of SIB in people with ID, especially when presented with a varied number of topographies, might provide guidance on ASD differential diagnosis.
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Transtorno do Espectro Autista/epidemiologia , Deficiência Intelectual/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Adolescente , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Características de Residência , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Schizotypy has been proposed to be the expression of genetic vulnerability to schizophrenia. The available literature shows cognitive similarities between schizotypy and schizophrenia, with mildly impaired performance being associated with schizotypy. This study aims to determine the relationship between schizotypy and cognitive performance in siblings of patients with psychosis. METHODS: Schizotypal features and cognitive performance on a neuropsychological battery were compared between 48 siblings of patients with psychosis and 44 healthy controls. The relationships between schizotypy and cognitive performance were analysed by controlling the condition of being a sibling. RESULTS: Siblings showed poorer performance on vigilance/sustained attention (M = 37.6; SD = 7.1) and selective attention/interference control/working memory (M = 23.28; SD = 2.7) tasks. The variance in vigilance/sustained attention performance was explained, at 30%, by the interpersonal factor of schizotypy on the suspiciousness dimension and the condition of being a sibling. CONCLUSIONS: Interpersonal features of schizotypy in siblings of patients with psychosis are associated with deficits in vigilance/sustained attention performance.
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Cognição , Transtornos Psicóticos , Transtorno da Personalidade Esquizotípica/psicologia , Irmãos/psicologia , Adulto , Atenção , Feminino , Humanos , Masculino , Memória de Curto Prazo , Testes Neuropsicológicos , Fenótipo , Transtornos Psicóticos/genética , Esquizofrenia/genética , Transtorno da Personalidade Esquizotípica/genética , Adulto JovemRESUMO
The objective of this study was to analyze the possible association between maternal attachment style and comorbidity associated with childhood ADHD. We evaluated a total of 103 children with ADHD treated at a Child and Adolescent Mental Health Centre and their mothers. Comorbidity was evaluated using the MINI-KID interview. Maternal attachment was evaluated using the Adult Attachment Questionnaire. We considered child variables that could be associated with the clinical course of ADHD, such as symptom severity, age, gender, evolution time, academic level, and current pharmacological treatment; parental variables, such as the mother's psychiatric history, current psychopathology, marital status, academic level, income, and employment, were also considered. We found an association between maternal insecure attachment and comorbid depressive disorder in childhood ADHD. An insecure maternal attachment style must be considered in the assessment and treatment of childhood ADHD with comorbid depression.
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Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Depressão/epidemiologia , Depressão/psicologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Relações Mãe-Filho/psicologia , Apego ao Objeto , Adulto , Criança , Comorbidade , Feminino , Humanos , Masculino , Espanha/epidemiologia , Adulto JovemRESUMO
The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic-pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT4<1.16ng/dL); 2) medium quartiles (Q2-Q3, FT4 1.16-1.54ng/dL); and 3) highest quartile (Q4, FT4>1.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients.
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Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia , Transtornos Psicóticos/complicações , Tiroxina/sangue , Adolescente , Adulto , Análise de Variância , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Tireotropina/sangue , Adulto JovemRESUMO
BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.
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Adaptação Psicológica , Transtornos de Ansiedade , Depressão Pós-Parto , Período Pós-Parto/psicologia , Apoio Social , Estresse Psicológico , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/prevenção & controle , Depressão Pós-Parto/psicologia , Feminino , Humanos , Acontecimentos que Mudam a Vida , Estudos Longitudinais , Neuroticismo , Determinação da Personalidade , Valor Preditivo dos Testes , Gravidez , Prognóstico , Técnicas Psicológicas , Fatores de Risco , Estatística como Assunto , Estresse Psicológico/complicações , Estresse Psicológico/diagnósticoRESUMO
Controversy exists about the role of parent psychopathology in persistence and severity of attention deficit hyperactivity disorder (ADHD) symptoms in their children. Here we aimed to analyse the potential association between the severity of ADHD symptoms in children and the presence of psychiatric and ADHD symptoms in their biological parents. Seventy-three triads of children and their parents who were in active treatment for their diagnosed ADHD were evaluated in our Child and Adolescent Mental Health Centers. The mental health of the parents was also assessed. The general psychopathology of the parents was evaluated using the Symptom Checklist-90-R (SCL-90-R), and symptoms of hyperactivity were examined using the Adult ADHD Self-Report Scale (ASRS v.1.1). The severity of symptoms in children was assessed using the ADHD Rating Scale-IV (ADHD-RS-IV). Variables that could have affected the clinical development of ADHD such as sex, evolution time, age, academic level and the presence of comorbidities were controlled. The severity of the symptoms in children with ADHD was significantly related to the psychiatric history of their mother, the younger age of the child and the presence of a comorbid conduct disorder in the child. We discussed the importance of screening for parental psychopathology in clinical practice.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Bem-Estar Materno/psicologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Saúde Mental , Pais/psicologiaRESUMO
OBJECTIVE: To review the scientific literature about the relationship between impairment on smooth pursuit eye movements and schizophrenia. METHODS: Narrative review that includes historical articles, reports about basic and clinical investigation, systematic reviews, and meta-analysis on the topic. RESULTS: Up to 80% of schizophrenic patients have impairment of smooth pursuit eye movements. Despite the diversity of test protocols, 65% of patients and controls are correctly classified by their overall performance during this pursuit. The smooth pursuit eye movements depend on the ability to anticipate the target's velocity and the visual feedback, as well as on learning and attention. The neuroanatomy implicated in smooth pursuit overlaps to some extent with certain frontal cortex zones associated with some clinical and neuropsychological characteristics of the schizophrenia, therefore some specific components of smooth pursuit anomalies could serve as biomarkers of the disease. Due to their sedative effect, antipsychotics have a deleterious effect on smooth pursuit eye movements, thus these movements cannot be used to evaluate the efficacy of the currently available treatments. CONCLUSION: Standardized evaluation of smooth pursuit eye movements on schizophrenia will allow to use specific aspects of that pursuit as biomarkers for the study of its genetics, psychopathology, or neuropsychology.
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Acompanhamento Ocular Uniforme , Esquizofrenia/fisiopatologia , Encéfalo/anatomia & histologia , Encéfalo/fisiopatologia , HumanosRESUMO
BACKGROUND: Some women experience thoughts of harming their infants during the early postpartum period. These intrusive thoughts are conceptually similar to obsessive-compulsive disorder. The aim of our study was to assess whether personality characteristics may predict a mother's development of postpartum thoughts of harming her infant. METHODS: We studied 137 women with no psychiatric history. They were assessed at two different times during the postpartum period (2-3days after giving birth and during the 8th week following delivery). We assessed postpartum thoughts of harming one's infant with a semi-structured interview conducted in person. Personality characteristics were assessed with the Eysenck Personality Questionnaire. Depression was assessed with the Edinburgh Postnatal Depression Scale and with a structured interview (Diagnostic Interview for Genetic Studies). We also assessed socio-demographic variables, obstetric variables and stressful life events. Adjusting for age, depression and stressful life events, logistic regression was conducted to explore the relationship between a woman's personality characteristics and postpartum thoughts of harming her infant. RESULTS: Women with postpartum thoughts of harming their infants scored higher in EPQ-Psychoticism (P=0.003) but not in neuroticism or extraversion. EPQ-Psychoticism was significantly associated with the presence of postpartum intrusive thoughts (OR=1.67, p=0.003) after adjusting for other personality dimensions, age, depression and life stress. Those women scoring 5 or higher in EPQ-Psychoticism were 5.5 times more likely to report postpartum intrusive thoughts (p=0.004). CONCLUSIONS: In healthy women without psychiatric history, psychoticism is a predictor of postpartum thoughts of harming their infants.
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Depressão Pós-Parto/psicologia , Mães/psicologia , Período Pós-Parto/psicologia , Transtornos Psicóticos/psicologia , Estresse Psicológico/psicologia , Adulto , Feminino , Humanos , Acontecimentos que Mudam a Vida , Estudos Prospectivos , PensamentoRESUMO
The poorly understood aetiology of schizophrenia is known to involve a major genetic contribution even though the genetic factors remain elusive. Most genetic studies are based on Mendelian rules and focus on the nuclear genome, but current studies indicate that other genetic mechanisms are probably involved. This review focuses on mitochondrial DNA (mtDNA), a maternally inherited, 16.6-Kb molecule crucial for energy production that is implicated in numerous human traits and disorders. The aim of this review is to summarise the studies that have explored mtDNA in schizophrenia patients and those which provide evidence for its implication in this illness. Alterations in mitochondrial morphometry, brain energy metabolism, and enzymatic activity in the mitochondrial respiratory chain suggest a mitochondrial dysfunction in schizophrenia that could be related to the genetic characteristics of mtDNA. Moreover, evidence of maternal inheritance and the presence of schizophrenia symptoms in patients suffering from a mitochondrial disorder related to an mtDNA mutation suggest that mtDNA is involved in schizophrenia. The association of specific variants has been reported at the molecular level; however, additional studies are needed to determine whether the mitochondrial genome is involved in schizophrenia.
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DNA Mitocondrial/genética , Esquizofrenia/genética , Humanos , Mitocôndrias/genética , Doenças Mitocondriais/complicações , Doenças Mitocondriais/genética , Polimorfismo Genético/genética , Esquizofrenia/etiologiaRESUMO
Recent findings suggest that glycogen synthase kinase 3ß (GSK3ß) may play a role in the pathophysiology and treatment of mood disorders. Various genetic studies have shown the association of GSK3ß polymorphisms with different mood disorder phenotypes. We hypothesized that genetic variants in the GSK3ß gene could partially underlie the susceptibility to mood disorders. We performed a genetic case-control study of 440 psychiatrically screened control subjects and 445 mood disorder patients [256 unipolar major depressive disorder (MDD) and 189 bipolar disorder (BD)]. We genotyped a set of 11 single nucleotide polymorphisms (SNPs) and determined the relative frequency of a known copy number variant (CNV) overlapping the GSK3ß by quantitative real-time polymerase chain reaction (PCR). We found no evidence of association with MDD or BD diagnosis, and we further investigated the age at onset (AAO) of the disorder and severity of depressive index episode. We found that rs334555, located in intron 1 of GSK3ß, was nominally associated with an earlier AAO of the disease in MDD (P = 0.001). We also identified a haplotype containing three SNPs (rs334555, rs119258668 and rs11927974) associated with AAO of the disorder (permutated P = 0.0025). We detected variability for the CNV, but we could not detect differences between patients and controls for any of the explored phenotypes. This study presents further evidence of the contribution of GSK3ß to mood disorders, implicating a specific SNP and a haplotype with an earlier onset of the disorder in a group of well-characterized patients with unipolar MDD. Further replication studies in patients with the same phenotypic characteristics should confirm the results reported here.
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Transtorno Depressivo Maior/genética , Quinase 3 da Glicogênio Sintase/genética , Adulto , Idade de Início , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Transtorno Depressivo Maior/psicologia , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Glicogênio Sintase Quinase 3 beta , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654 schizophrenic patients and 604 controls for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39 Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability to schizophrenia (odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.
Assuntos
Dosagem de Genes/genética , Glutationa Transferase/genética , Esquizofrenia/genética , Adulto , Idoso , Feminino , Duplicação Gênica/genética , Predisposição Genética para Doença/epidemiologia , Variação Genética , Genômica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Esquizofrenia/epidemiologiaRESUMO
Personality dimensions have been associated with symptoms dimensions in schizophrenic patients (SP). In this paper we study the relationships between symptoms of functional psychoses and personality dimensions in SP and their first-degree relatives (SR), in other psychotic patients (PP) and their first-degree relatives (PR), and in healthy controls in order to evaluate the possible clinical dimensionality of these disorders. Twenty-nine SP, 29 SR, 18 PP, 18 PR and 188 controls were assessed using the temperament and character inventory (TCI-R). Current symptoms were evaluated with positive and negative syndrome scale (PANSS) using the five-factor model described previously (positive [PF], negative [NF], disorganized [DF], excitement [EF] and anxiety/depression [ADF]). Our TCI-R results showed that patients had different personality dimensions from the control group, but in relatives, these scores were not different from controls. With regard to symptomatology, we highlight the relations observed between harm avoidance (HA) and PANSS NF, and between self-transcendence (ST) and PANSS PF. From a personality traits-genetic factors point of view, schizophrenia and other psychosis may be initially differentiated by temperamental traits such as HA. The so-called characterial traits like ST would be associated with the appearance of psychotic symptoms.
Assuntos
Caráter , Transtornos Psicóticos/genética , Esquizofrenia/genética , Psicologia do Esquizofrênico , Temperamento , Adulto , Feminino , Predisposição Genética para Doença/genética , Redução do Dano , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria/estatística & dados numéricos , Psicopatologia , Transtornos Psicóticos/psicologia , Valores de Referência , Esquizofrenia/diagnósticoRESUMO
BACKGROUND: Polymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in 5-HTT may play a similar role in the post-partum period. AIMS: To study the role of 5-HTT polymorphic variations in mood changes after delivery. METHOD: One thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2-3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of 5-HTT (5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of 5-HTT expression. RESULTS: One hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression 5-HTT genotypes in a dose-response fashion at 8 weeks post-partum, but not at 32 weeks. CONCLUSIONS: High-expression 5-HTT genotypes may render women more vulnerable to depressive symptoms after childbirth.