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BACKGROUND: Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.AimsTo examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability. METHOD: Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54-1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3-9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6-50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97. CONCLUSIONS: Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.Declaration of interestNone.
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Discapacidad Intelectual/epidemiología , Trastornos Psicóticos/epidemiología , Adolescente , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Escocia/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Negative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques. AIMS: To examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms. METHOD: A total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart. RESULTS: When comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus. CONCLUSIONS: Negative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.
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Cerebelo/patología , Corteza Cerebral/patología , Progresión de la Enfermedad , Sustancia Gris/patología , Trastornos Psicóticos/patología , Trastornos Psicóticos/fisiopatología , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Lóbulo Temporal/patología , Adolescente , Adulto , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Psicóticos/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Adulto JovenRESUMEN
Nonlinear Dynamic Causal Modelling (DCM) for fMRI provides computational modelling of gating mechanisms at the neuronal population level. It allows for estimations of connection strengths with nonlinear modulation within task-dependent networks. This paper presents an application of nonlinear DCM in subjects at high familial risk of schizophrenia performing the Hayling Sentence Completion Task (HSCT). We analysed scans of 19 healthy controls and 46 subjects at high familial risk of schizophrenia, which included 26 high risk subjects without psychotic symptoms and 20 subjects with psychotic symptoms. The activity-dependent network consists of the intra parietal cortex (IPS), inferior frontal gyrus (IFG), middle temporal gyrus (MTG), anterior cingulate cortex (ACC) and the mediodorsal (MD) thalamus. The connections between the MD thalamus and the IFG were gated by the MD thalamus. We used DCM to investigate altered connection strength of these connections. Bayesian Model Selection (BMS) at the group and family level was used to compare the optimal bilinear and nonlinear models. Bayesian Model Averaging (BMA) was used to assess the connection strengths with the gating from the MD thalamus and the IFG. The nonlinear models provided the better explanation of the data. Furthermore, the BMA analysis showed significantly lower connection strength of the thalamocortical connection with nonlinear modulation from the MD thalamus in high risk subjects with psychotic symptoms and those who subsequently developed schizophrenia. These findings demonstrate that nonlinear DCM provides a method to investigate altered connectivity at the level of neural circuits. The reduced connection strength with thalamic gating may be a neurobiomarker implicated in the development of psychotic symptoms. This study suggests that nonlinear DCM could lead to new insights into functional and effective dysconnection at the network level in subjects at high familial risk.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esquizofrenia/genética , Adolescente , Algoritmos , Teorema de Bayes , Encéfalo/patología , Deluciones/patología , Deluciones/psicología , Femenino , Predisposición Genética a la Enfermedad , Alucinaciones/patología , Alucinaciones/psicología , Humanos , Modelos Lineales , Masculino , Modelos Neurológicos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Dinámicas no Lineales , Desempeño Psicomotor/fisiología , Riesgo , Psicología del Esquizofrénico , Tálamo/patología , Adulto JovenRESUMEN
A masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication - that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.
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Lenguaje , Esquizofrenia/diagnóstico , Estudios de Casos y Controles , Humanos , Pruebas Neuropsicológicas , Estudios Prospectivos , Esquizofrenia/genética , Grabación de Cinta de Video , Adulto JovenRESUMEN
BACKGROUND: No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia. AIMS: To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance. RESULTS: Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F= 7.66, P= 0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis. CONCLUSIONS: These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.
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Cannabis/efectos adversos , Predisposición Genética a la Enfermedad , Abuso de Marihuana/patología , Esquizofrenia/patología , Tálamo/patología , Adolescente , Adulto , Amígdala del Cerebelo/patología , Análisis de Varianza , Progresión de la Enfermedad , Femenino , Hipocampo/patología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Fumar Marihuana/efectos adversos , Factores de Riesgo , Esquizofrenia/epidemiología , Esquizofrenia/genética , Tálamo/efectos de los fármacos , Factores de Tiempo , Adulto JovenRESUMEN
The limitations of current diagnostic categories are well recognised but their rationale, advantages and utility are often ignored. The scientific support for a 'continuum of psychosis' is limited, and the examination of whether categories, a continuum or more than one continua, and alternatives such as subtypes or hybrid models, best account for the distributions of symptoms in populations has simply not been done. There is a lack of discussion, let alone consensus, about the critical aspects of psychosis to measure, the best ways to quantify those and how these would be applied in clinical practice. Systematic studies are needed to evaluate which of a range of plausible approaches to the classification of psychosis is most useful before change could be justified.
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Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Mentales/clasificación , Humanos , Trastornos Mentales/diagnósticoRESUMEN
BACKGROUND: Although neuroanatomical and cognitive sequelae of low birthweight and preterm birth have been investigated, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population. Our aim was to address these issues in a sample of young people receiving additional learning support. METHODS: One hundred and thirty-seven participants aged 13-22 years, receiving additional learning support, were recruited via their schools or colleges and underwent structural magnetic resonance imaging (MRI). Obstetric records, available in 98 cases, included birthweight and gestational data in 90 and 95 cases, respectively. Both qualitative and quantitative voxel-based analyses of MRI data were conducted. RESULTS: A history of low birthweight and preterm birth was present in 13.3% and 13.7% of cases, respectively. Low birthweight and preterm birth were associated with specific qualitative anomalies, including enlargement of subarachnoid cisterns and thinning of the corpus callosum. Low birthweight was associated with reduced grey matter density (GMD) in the superior temporal gyrus (STG) bilaterally, left inferior temporal gyrus and left insula. Prematurity of birth was associated with reduced GMD in the STG bilaterally, right inferior frontal gyrus and left cerebellar hemisphere. Comparison of subjects with no history of low birthweight or preterm birth with a previously defined control sample of cognitively unimpaired adolescents (n = 72) demonstrated significantly greater scores for several anomalies, including thinning of the corpus callosum, loss of white matter and abnormalities of shape of the lateral ventricles. CONCLUSION: Although a two-fold increased prevalence of a history of low birthweight and preterm birth exists within the special educational needs population, other aetiological factors must be considered for the overwhelming majority of cases. Neuroanatomical findings within this sample include qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. These findings suggest a neurodevelopmental mechanism for the cognitive difficulties associated with these obstetric risk factors.
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Educación Especial , Recién Nacido de Bajo Peso , Nacimiento Prematuro/epidemiología , Adolescente , Adulto , Peso al Nacer , Encéfalo/anatomía & histología , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Embarazo , Prevalencia , Factores de RiesgoRESUMEN
This article reviews the evidence for changes in the structure and function of the brain in subjects at high risk of schizophrenia for genetic reasons during the genesis of the disorder. We first highlight the structural and functional abnormalities in schizophrenia and whether any similar or lesser abnormalities are apparent in unaffected relatives. There is good evidence for subtle abnormalities of hippocampal and ventricle volume in relatives that are not as marked as the deficits in schizophrenia. In addition, the functional imaging literature suggests that prefrontal cortex function may deteriorate in those at risk who go on to develop the disorder. We then review the findings from longitudinal imaging studies of those at high risk, particularly the Edinburgh High-Risk Study, which report gray matter density reductions in medial and lateral temporal lobe because people develop schizophrenia, as well as functional abnormalities which precede onset. We conclude by quoting our own and others' imaging studies of the associations of genetic and other risk factors for schizophrenia, including stressful life events and cannabis use, which provide mechanistic examples of how these changes may be brought about. Overall, the literature supports the view that there are measurable changes in brain structure and function during the genesis of the disorder, which provide opportunities for early detection and intervention.
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Encéfalo/anatomía & histología , Encéfalo/fisiopatología , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Catecol O-Metiltransferasa/genética , Electroencefalografía , Expresión Génica/genética , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Abuso de Marihuana/epidemiología , Factores de Riesgo , Esquizofrenia/epidemiología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Gemelos/genéticaRESUMEN
Theory of Mind, Weak Central Coherence and executive dysfunction, were investigated as a function of behavioural markers of autism. This was irrespective of the presence or absence of a diagnosis of an autistic spectrum disorder. Sixty young people completed the Social Communication Questionnaire (SCQ), false belief tests, the block design test, viewed visual illusions and an ambiguous figure. A logistic regression was performed and it was found that Theory of Mind, central coherence and ambiguous figure variables significantly contributed to prediction of behavioural markers of autism. These findings provide support for the continuum hypothesis of autism. That is, mild autistic behavioural traits are distributed through the population and these behavioural traits may have the same underlying cognitive determinants as autistic disorder.
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Trastorno Autístico/complicaciones , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Percepción de Forma , Fenotipo , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pruebas Neuropsicológicas , Trastornos de la Percepción/diagnóstico , Trastornos de la Percepción/etiología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In our cohort considered at high risk (HR) of developing schizophrenia, we previously found a significant difference in extent of right prefrontal cortical folding between those who subsequently developed schizophrenia and a matched group who remained well. This study aimed to determine if this preexisting difference distinguished 17 individuals who developed schizophrenia from the 128 HR individuals in the cohort who remained well and to explore possible underlying differences in cortical composition. METHODS: Prefrontal cortical folding was measured by an automated version of the Gyrification Index (A-GI), a ratio reflecting extent of folding. Multivariate logistic regression assessed the probability that prefrontal A-GI predicts diagnostic outcome and subsequently assessed the effect on A-GI of regional cerebrospinal fluid and gray and white matter. RESULTS: High-risk individuals who subsequently developed schizophrenia were distinguished from the remaining cohort by increased right prefrontal cortex (PFC) A-GI. Mean right PFC gray matter volume also differed between groups, but white matter volume did not. Correlations of age with gray and white matter further distinguished groups and a linear regression analysis showed a significant interaction between age and diagnosis on mean volume of right PFC white matter. CONCLUSIONS: Increased A-GI appears to indicate abnormal right prefrontal development in those who develop schizophrenia.
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Corteza Prefrontal/crecimiento & desarrollo , Corteza Prefrontal/patología , Esquizofrenia/patología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Corteza Prefrontal/anomalías , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Riesgo , Esquizofrenia/líquido cefalorraquídeoRESUMEN
BACKGROUND: There is growing evidence that the gene catechol-O-methyltransferase (COMT) is involved in the etiopathogenesis of schizophrenia. This study sought to clarify the effects of the COMT Val158Met polymorphism on brain structure, function, and risk of developing schizophrenia in a well-characterized cohort of individuals at high risk of schizophrenia for familial reasons. METHODS: In a sample of 78 people at high genetic risk of schizophrenia, the risk of progression to schizophrenia associated with the COMT Val allele was estimated. The relationship of the Val allele to brain structure and function was investigated using structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) data collected on the high-risk subjects before their disease outcome was known. RESULTS: The COMT Val allele increased the risk of schizophrenia in this cohort in a dose-dependent manner. Subjects with the COMT Val allele had reduced gray matter density in anterior cingulate cortex. In addition, there was evidence of increased activation in lateral prefrontal cortex and anterior and posterior cingulated, with increasing sentence difficulty in those with the COMT Val allele despite a similar level of performance. CONCLUSIONS: The COMT Val allele is associated with an increased risk of schizophrenia in subjects at increased familial risk, in whom it has demonstrable effects on prefrontal brain structure and function. These patterns of altered brain structure and function have previously been associated with schizophrenia in this and other samples.
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Sustitución de Aminoácidos/genética , Encéfalo/fisiopatología , Catecol O-Metiltransferasa/genética , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Imagen por Resonancia Magnética , Metionina/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Valina/genética , Adolescente , Adulto , Alelos , Encéfalo/patología , Estudios de Cohortes , Dominancia Cerebral/fisiología , Dopamina/metabolismo , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad/genética , Genotipo , Giro del Cíngulo/patología , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Pruebas Neuropsicológicas , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Factores de Riesgo , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Lenguaje del Esquizofrénico , Psicología del Esquizofrénico , EscociaRESUMEN
BACKGROUND: It has been proposed that different types of psychopathology in schizophrenia may reflect distinguishable pathological processes. In the current study we aimed to address such associations in the absence of confounders such as medication and disease chronicity by examining specific relationships between fMRI activation and individual symptom severity scores in un-medicated subjects at high genetic risk of schizophrenia. METHODS: Associations were examined across two functional imaging paradigms: the Hayling sentence completion task, and an encoding/retrieval task, comprising encoding (at word classification) and retrieval (old word/new word judgement). Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Items examined were hallucinations, delusions, and suspiciousness/persecution. RESULTS: Associations were seen in the anterior middle temporal gyrus in relation to hallucination scores during the sentence completion task, and in the medial temporal lobe in association with suspiciousness/persecution scores in the encoding/retrieval task. Cerebellar activation was associated with delusions and suspiciousness/persecution scores across both tasks with differing patterns of laterality. CONCLUSION: These results support a role for the lateral temporal cortex in hallucinations and medial temporal lobe in positive psychotic symptoms. They also highlight the potential role of the cerebellum in the formation of delusions. That the current results are seen in un-medicated high risk subjects indicates these associations are not specific to the established illness and are not related to medication effects.
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Encéfalo/fisiopatología , Deluciones/genética , Deluciones/fisiopatología , Alucinaciones/genética , Alucinaciones/fisiopatología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas/estadística & datos numéricos , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Adolescente , Adulto , Ganglios Basales/fisiopatología , Mapeo Encefálico , Cerebelo/fisiopatología , Cultura , Deluciones/diagnóstico , Deluciones/psicología , Dominancia Cerebral/fisiología , Femenino , Lóbulo Frontal/fisiopatología , Predisposición Genética a la Enfermedad/genética , Alucinaciones/diagnóstico , Alucinaciones/psicología , Hipocampo/fisiopatología , Humanos , Masculino , Recuerdo Mental/fisiología , Lóbulo Parietal/fisiopatología , Psicometría , Desempeño Psicomotor/fisiología , Factores de Riesgo , Esquizofrenia/diagnóstico , Estadística como Asunto , Lóbulo Temporal/fisiopatología , Tálamo/fisiopatología , Aprendizaje Verbal/fisiología , Pruebas de Asociación de PalabrasRESUMEN
To date, there are no reliable markers for predicting onset of schizophrenia in individuals at high risk (HR). Substantial promise is, however, shown by a variety of pattern classification approaches to neuroimaging data. Here, we examined the predictive accuracy of support vector machine (SVM) in later diagnosing schizophrenia, at a single-subject level, using a cohort of HR individuals drawn from multiply affected families and a combination of neuroanatomical, schizotypal and neurocognitive variables. Baseline structural magnetic resonance imaging (MRI), schizotypal and neurocognitive data from 17 HR subjects, who subsequently developed schizophrenia and a matched group of 17 HR subjects who did not make the transition, yet had psychotic symptoms, were included in the analysis. We employed recursive feature elimination (RFE), in a nested cross-validation scheme to identify the most significant predictors of disease transition and enhance diagnostic performance. Classification accuracy was 94% when a self-completed measure of schizotypy, a declarative memory test and structural MRI data were combined into a single learning algorithm; higher than when either quantitative measure was used alone. The discriminative neuroanatomical pattern involved gray matter volume differences in frontal, orbito-frontal and occipital lobe regions bilaterally as well as parts of the superior, medial temporal lobe and cerebellar regions. Our findings suggest that an early SVM-based prediction of schizophrenia is possible and can be improved by combining schizotypal and neurocognitive features with neuroanatomical variables. However, our predictive model needs to be tested by classifying a new, independent HR cohort in order to estimate its validity.
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Encéfalo/diagnóstico por imagen , Diagnóstico por Computador , Memoria , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Trastorno de la Personalidad Esquizotípica/psicología , Adolescente , Adulto , Cognición , Familia , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Pruebas Neuropsicológicas , Esquizofrenia/clasificación , Esquizofrenia/genética , Máquina de Vectores de Soporte , Adulto JovenRESUMEN
BACKGROUND: Prospective studies of young individuals at high risk of schizophrenia allow the investigation of whether neural abnormalities predate development of illness and, if present, have the potential to identify those who may become ill. METHODS: We studied young individuals with at least two relatives with the disorder. At baseline functional magnetic resonance imaging (fMRI) scan, none met criteria for any psychiatric disorder, but four subjects subsequently developed schizophrenia. We report the baseline functional imaging findings in these subjects performing a sentence completion task compared with normal control subjects (n = 21) and those at high risk with (n = 21) and without (n = 41) psychotic symptoms who have not developed the disorder. RESULTS: High-risk subjects who became ill demonstrated increased activation of the parietal lobe, decreased activation of the anterior cingulate, and smaller increases in activation with increasing task difficulty in the right lingual gyrus and bilateral temporal regions. The hypothesized predictive power of parietal activation was supported only in combination with lingual gyrus activity, which gave a positive predictive value in this sample of .80. CONCLUSIONS: Although these findings should be considered cautiously, as only four subjects who had an fMRI scan subsequently became ill, they suggest functional abnormalities are present in high-risk subjects who later became ill, which distinguish them not only from normal control subjects but also those at high risk who had not developed the disorder. These differences are detectable with fMRI and may have clinical utility.
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Mapeo Encefálico , Corteza Cerebral/fisiología , Imagen por Resonancia Magnética , Esquizofrenia/diagnóstico , Conducta Verbal/fisiología , Adolescente , Adulto , Corteza Cerebral/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Giro del Cíngulo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Metaloporfirinas , Lóbulo Parietal/fisiología , Linaje , Valor Predictivo de las Pruebas , Valores de Referencia , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Lóbulo Temporal/fisiologíaRESUMEN
BACKGROUND: We hypothesised that subjects at familial high risk of developing schizophrenia would have a reduction over time in grey matter, particularly in the temporal lobes, and that this reduction may predict schizophrenia better than clinical measurements. METHODS: We analysed magnetic resonance images of 65 high-risk subjects from the Edinburgh High Risk Study sample who had two scans a mean of 1.52 years apart. Eight of these 65 subjects went on to develop schizophrenia an average of 2.3 years after their first scan. RESULTS: Changes over time in the inferior temporal gyrus gave a 60% positive predictive value (likelihood ratio >10) of developing schizophrenia compared to the overall 13% risk in the cohort as a whole. CONCLUSION: Changes in grey matter could be used as part of a predictive test for schizophrenia in people at enhanced risk for familial reasons, particularly for positive predictive power, in combination with other clinical and cognitive predictive measures, several of which are strong negative predictors. However, because of the limited number of subjects, this test requires independent replication to confirm its validity.
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Encéfalo/patología , Esquizofrenia/patología , Humanos , Valor Predictivo de las Pruebas , Riesgo , Esquizofrenia/genética , Lóbulo Temporal/patologíaRESUMEN
Schizophrenia is a highly heritable psychotic disorder. It has been suggested that deficits of the established state arise from abnormal interactions between brain regions. We sought to examine whether such connectivity abnormalities would be present in subjects at high genetic risk for the disorder. Functional connectivity analysis was carried out on functional MRI images from 21 controls and 69 high risk subjects performing the Hayling sentence completion task; 27 high risk subjects reported isolated psychotic symptoms, the remaining high risk subjects and controls did not. There were no significant differences in task performance between the groups. Based on previous findings we hypothesized: (i) state-related differences in connectivity between dorsolateral prefrontal cortex and lateral temporal lobe; (ii) genetically mediated reductions in a medial prefrontal-thalamic-cerebellar network; and (iii) increased prefrontal-parietal connectivity in high risk subjects (to a greater extent in those with isolated psychotic symptoms). Connectivity analysis was performed in two ways: with and without variance associated with task effects modelled and removed from the data. We did not find evidence to support our first hypothesis with either analysis method. However, consistent with hypothesis (ii), decreased connectivity between right medial prefrontal regions and contralateral cerebellum was found. This was only statistically significant in the analysis with task effects modelled and removed from the data. Finally, consistent with hypothesis (iii), increased connectivity between the left parietal and left prefrontal regions in high risk subjects was found in both analyses. These results, all in a situation uncontaminated by the effects of anti-psychotic medication, performance differences and prolonged illness, suggest there are abnormalities in functional connectivity over and above those attributable to task effects in high risk subjects. These connectivity abnormalities may underlie the diverse deficits seen in the established condition and the more subtle deficits seen in close relatives of those with the disorder.
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Predisposición Genética a la Enfermedad , Esquizofrenia/genética , Adolescente , Adulto , Mapeo Encefálico/métodos , Cerebelo/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Corteza Prefrontal/fisiopatología , Trastornos Psicóticos/genética , Trastornos Psicóticos/fisiopatología , Trastornos Psicóticos/psicología , Esquizofrenia/fisiopatología , Lóbulo Temporal/fisiopatologíaRESUMEN
Grey matter brain networks are disrupted in schizophrenia, but it is still unclear at which point during the development of the illness these disruptions arise and whether these can be associated with behavioural predictors of schizophrenia. We investigated if single-subject grey matter networks were disrupted in a sample of people at familial risk of schizophrenia. Single-subject grey matter networks were extracted from structural MRI scans of 144 high risk subjects, 32 recent-onset patients and 36 healthy controls. The following network properties were calculated: size, connectivity density, degree, path length, clustering coefficient, betweenness centrality and small world properties. People at risk of schizophrenia showed decreased path length and clustering in mostly prefrontal and temporal areas. Within the high risk sample, the path length of the posterior cingulate cortex and the betweenness centrality of the left inferior frontal operculum explained 81% of the variance in schizotypal cognitions, which was previously shown to be the strongest behavioural predictor of schizophrenia in the study. In contrast, local grey matter volume measurements explained 48% of variance in schizotypy. The present results suggest that single-subject grey matter networks can quantify behaviourally relevant biological alterations in people at increased risk for schizophrenia before disease onset.
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Encéfalo/patología , Sustancia Gris/patología , Red Nerviosa/patología , Esquizofrenia/patología , Adolescente , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Síntomas Prodrómicos , Escalas de Valoración Psiquiátrica , Riesgo , Esquizofrenia/genética , Adulto JovenRESUMEN
It has been suggested that low frequency transcranial magnetic stimulation (TMS) over left temporo-parietal cortex may reduce the frequency and intensity of auditory hallucinations in schizophrenia. Sixteen patients with hallucinations, treatment-resistant for at least 2 months, were randomised into a placebo-controlled crossover study of TMS at 1 Hz and 80% of motor threshold over left temporo-parietal cortex. Treatment periods lasted for 4 days, with daily duration escalating from 4 to 8, 12 and 16 min on subsequent days. Each minute of stimulation was followed by 15 s of rest to check coil position and allow the patient to move, if necessary. Both patients and symptom raters were unaware of the treatment condition. Patients' hallucination scores improved from baseline with both real and sham TMS, and there was no significant difference between real and sham treatments. There was a trend for second treatments, whether sham or real, to be more effective than first treatments. Other psychopathology scales (apart from positive symptoms) and verbal memory were not affected by real or sham TMS. Previous positive studies could not be replicated with these parameters. TMS is safe if applied within the protocol used.
Asunto(s)
Alucinaciones/etiología , Alucinaciones/terapia , Esquizofrenia/complicaciones , Estimulación Magnética Transcraneal/instrumentación , Adolescente , Adulto , Anciano , Estudios Cruzados , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico , CráneoRESUMEN
UNLABELLED: There have been concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations. A screening tool for ASDs in prisons has therefore been developed. AIMS: We aimed to evaluate this tool in Scottish prisoners by comparing scores with standard measures of autistic traits (Autism Quotient (AQ)), neurodevelopmental history (Asperger Syndrome (and High-Functioning Autism) Diagnostic Interview (ASDI)), and social cognition (Ekman 60 Faces test). METHODS: Prison officers across all 12 publicly-run closed prisons in Scotland assessed convicted prisoners using the screening tool. This sample included male and female prisoners and both adult and young offenders. Prisoners with high scores, along with an equal number of age and sex-matched controls, were invited to take part in interviews. Prisoners' relatives were contacted to complete a neurodevelopmental assessment. RESULTS: 2458 prisoners were screened using the tool, and 4% scored above the cut-off. 126 prisoners were further assessed using standardised measures. 7 of those 126 assessed scored 32 or above (cut-off) on the AQ. 44 interviews were completed with prisoners' relatives, no prisoner reached the cut-off score on the ASDI. Scores on the screening tool correlated significantly with AQ and ASDI scores, and not with the Ekman 60 Faces Test or IQ. Sensitivity was 28.6% and specificity 75.6%; AUC was 59.6%. CONCLUSIONS: Although this screening tool measures autistic traits in this population, sensitivity for scores of 32 or above on the AQ is poor. We consider that this limits its usefulness and do not recommend that the tool is routinely used to screen for ASDs in prisons.
Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Tamizaje Masivo/métodos , Prisioneros , Adolescente , Adulto , Niño , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Preescolar , Femenino , Humanos , Lactante , Inteligencia , Masculino , Curva ROC , Escocia/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Studies of antisocial populations have found that they show deficits in recognition of facial affect. Such deficits are also found in other populations with clinical conditions such as autism spectrum disorders, schizophrenia and obsessive compulsive disorder. AIMS: We aimed to investigate the hypothesis that facial affect recognition in the Scottish prison population would differ from matched controls. In addition, we aimed to investigate any relationship between facial affect recognition deficits and offence history. METHODS: A sample of serving convicted prisoners, drawn from a larger study, was assessed for ability to recognise facial affect. Other variables were also measured and a self-report offending history obtained. RESULTS: 127 prisoners were assessed in 11 prisons. Male prisoners were significantly worse than age, sex and IQ-matched controls at recognising negative facial emotions, specifically anger, fear, sadness and disgust. Within the sample of prisoners, deficits in fear recognition were associated with a history of previous prison sentences but not previous convictions. With respect to offending history, sex offenders were relatively better at recognising sadness and worse at recognising surprise than the other offenders. These relationships remain after controlling for IQ. CONCLUSIONS: Scottish convicted prisoners show deficits in recognising negative facial emotions in a pattern consistent with other antisocial populations. We also demonstrated a relationship between particular patterns of deficit and types of offending history not previously described.