RESUMEN
Borderline personality disorder (BPD) has repeatedly been linked to alterations in fronto-limbic dysfunction. In this study, we tested the hypothesis of disturbed structural connectivity in underlying fibre tracts and their relation to symptom profiles. We analysed diffusion tensor imaging (DTI) data from 18 female BPD patients and 38 female healthy controls. Group comparisons showed significant (pâ¯<â¯.05, FDR adjusted) increase of radial diffusivity (RD) in the right frontal lobe, including the uncinate fasciculus, anterior thalamic radiation, and inferior fronto-occipital fasciculus, as well as overall apparent diffusion coefficient (ADC) increases in the anterior and posterior internal capsule. Symptom correlations, based on the BSL-95 questionnaires, within the BPD sample showed significant negative correlations of dysphoria with ADC the left and right anterior thalamic radiation, and positive correlations of fractional anisotropy with self-perception scores in the right superior corona radiata. While our findings add to the fronto-limbic dysfunction model of BPD, they provide additional evidence of links to its affective core pathology, particularly frontotemporal and fronto-thalamic systems.
Asunto(s)
Trastorno de Personalidad Limítrofe , Sustancia Blanca , Anisotropía , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Encéfalo , Imagen de Difusión Tensora , Femenino , Humanos , Red Nerviosa , Sustancia Blanca/diagnóstico por imagenRESUMEN
Schizophrenia has been linked to disturbed connectivity between large-scale brain networks. Altered thalamocortical connectivity might be a major mechanism mediating regionally distributed dysfunction, yet it is only incompletely understood. We analysed functional magnetic resonance imaging data obtained during resting state from 22 DSM-IV schizophrenia patients and 22 matched healthy controls to directly assess the differences in thalamocortical functional connectivity. We identified significantly higher overall thalamocortical functional connectivity in patients, which was mostly accounted for by difference in thalamic connections to right ventrolateral prefrontal and bilateral secondary motor and sensory (superior temporal and lateral occipital) cortical areas. Voxelwise analysis showed group differences at the thalamic level to be mostly in medial and anterior thalamic nuclei and arising thalamocortical changes to be mostly due to higher positive correlations in prefrontal and superior temporal correlations, as well as absent negative correlations to sensory areas in patients. Our findings demonstrate that different types of thalamocortical dysfunction contribute to network alterations, including lack of inhibitory interaction attributed to the lack of significant negative thalamic/sensory cortical connections. These results emphasize the functional importance of the thalamus in the pathophysiology of schizophrenia.
Asunto(s)
Corteza Cerebral/patología , Vías Nerviosas/patología , Descanso/fisiología , Esquizofrenia/patología , Tálamo/patología , Adulto , Mapeo Encefálico , Corteza Cerebral/irrigación sanguínea , Imagen Eco-Planar , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Esquizofrenia/fisiopatología , Adulto JovenRESUMEN
AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
Asunto(s)
Trastornos Psicóticos , Humanos , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/diagnóstico , Síntomas ProdrómicosRESUMEN
This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Estudios Prospectivos , Adulto , Síntomas Prodrómicos , Adulto Joven , Cooperación Internacional , Adolescente , Proyectos de Investigación/normas , Masculino , FemeninoRESUMEN
Antipsychotic drug action might include mechanisms related to normalising phospholipid and high-energy metabolism. We applied brain metabolic imaging with (31)P magnetic resonance spectroscopy ((31)P MRS) and two-dimensional chemical shift imaging to assess changes of metabolism of phospholipids and high-energy phosphates in schizophrenia patients at baseline (four antipsychotic-naïve and three off antipsychotics) and at follow-up, after 6 weeks of treatment with olanzapine. Results indicate a significant increase of adenosine-triphosphate (ATP) in the right inferior temporal cortex and a trend towards ATP decrease in the left cerebellum. This suggests a shift in high-energy phosphates (rather than phospholipids), possibly related to normalisation of functioning in these areas.
Asunto(s)
Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Metabolismo Energético/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Adulto , Biomarcadores/metabolismo , Metabolismo Energético/fisiología , Femenino , Estudios de Seguimiento , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Olanzapina , Isótopos de Fósforo , Proyectos Piloto , Esquizofrenia/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: The ultra-high risk (UHR) paradigm allows the investigation of individuals at increased risk of developing psychotic or other mental disorders with the aim of making prevention and early intervention as specific as possible in terms of the individual outcome. METHODS: Single-session 1H-/31P-Chemical Shift Imaging of thalamus, prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices was applied to 69 UHR patients for psychosis and 61 matched healthy controls. N-acetylaspartate (NAA), glutamate/glutamine complex (Glx), energy (PCr, ATP) and phospholipid metabolites were assessed, analysed by ANOVA (or ANCOVA [with covariates]) and correlated with symptomatology (SCL-90R). RESULTS: The thalamus showed decreased NAA, inversely correlated with self-rated aggressiveness, as well as increased PCr, and altered phospholipid breakdown. While the aMCC showed a pattern of NAA decrease and PCr increase, the DLPFC showed PCr increase only in the close-to-psychosis patient subgroup. There were no specific findings in transition patients. CONCLUSION: The results do not support the notion of a specific pre-psychotic neurometabolic pattern, but likely reflect correlates of an "at risk for mental disorders syndrome". This includes disturbed neuronal (mitochondrial) metabolism in the thalamus and aMCC, with emphasis on left-sided structures, and altered PL remodeling across structures.
Asunto(s)
Ácido Glutámico , Trastornos Psicóticos , Ácido Aspártico/metabolismo , Ácido Glutámico/metabolismo , Humanos , Fosfolípidos/metabolismo , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/metabolismo , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/metabolismo , Tálamo/diagnóstico por imagen , Tálamo/metabolismoRESUMEN
BACKGROUND: The ultra-high risk (UHR) paradigm allows early contact with patients developing acute psychosis and the study of treatment effects on the underlying pathology. METHODS: 29 patients with first acute psychosis according to CAARMS criteria (transition patients, TP) (T0) and thereof 22 patients after two-year follow-up (mean 788 d) (T1) underwent 1H-/31P-MR spectroscopy of the prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices and the thalamus. N-acetylaspartate (NAA), glutamate (Glu, Glx), energy (PCr, ATP) and phospholipid metabolites (PME, PDE) were compared to 27 healthy controls by ANCOVA and correlated with patients' symptom ratings (BPRS-E, SCL-90R). For longitudinal analysis, linear mixed model (LMM) and ANCOVA for repeated measures were used. RESULTS: DLPFC: In patients, NAA and PME were decreased bilaterally and Glu on the left side at T0. Left-sided Glu and NAA (trend) and bilateral Glx increased during follow-up. Thalamus: In TP, bilateral NAA, left-sided Glu and right-sided Glx were decreased at T0; bilateral NAA and left-sided Glx increased during follow-up. aMCC: In TP, bilateral NAA, right-sided Glu, and bilateral PME and PDE were decreased, while left-sided PCr was increased at T0. No changes were observed during follow-up. CONCLUSION: Regardless of the long-term diagnosis, the psychotic state of illness includes disturbed neuronal function in the DLPFC, thalamus and aMCC. Treatment-as-usual (TAU), including antipsychotic/antidepressant medication and supportive psychotherapy, had an effect on the thalamo-frontal area but not or less pronounced on the neurometabolic deficits of the aMCC.
Asunto(s)
Trastornos Psicóticos , Ácido Aspártico , Estudios de Seguimiento , Humanos , Espectroscopía de Resonancia Magnética , Corteza Prefrontal/diagnóstico por imagen , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/tratamiento farmacológico , Tálamo/diagnóstico por imagenRESUMEN
BACKGROUND: Psychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects. METHODS: We analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition. RESULTS: Positive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations. CONCLUSION: Our results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation.
Asunto(s)
Corteza Cerebral , Cognición , Depresión , Inteligencia , Trastornos Psicóticos , Adulto , Corteza Cerebral/anatomía & histología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/crecimiento & desarrollo , Cognición/fisiología , Depresión/diagnóstico por imagen , Depresión/patología , Depresión/fisiopatología , Endofenotipos , Femenino , Humanos , Inteligencia/fisiología , Imagen por Resonancia Magnética , Masculino , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/patología , Trastornos Psicóticos/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Borderline personality disorder (BPD) presents with symptoms across different domains, whose neurobiology is poorly understood. METHODS: We applied voxel-based morphometry on high-resolution magnetic resonance imaging scans of 19 female BPD patients and 50 matched female controls. RESULTS: Group comparison showed bilateral orbitofrontal gray matter loss in patients, but no significant changes in the hippocampus. Voxel-wise correlation of gray matter with symptom severity scores from the Borderline Symptom List (BSL-95) showed overall negative correlation in bilateral prefrontal, right inferior temporal/fusiform and occipital cortices, and left thalamus. Significant (negative) correlations with BSL-95 subscores within the patient cohort linked autoaggression to left lateral prefrontal and insular cortices, right inferior temporal/temporal pole, and right orbital cortex; dysthymia/dysphoria to right orbitofrontal cortex; self-perception to left postcentral, bilateral inferior/middle temporal, right orbitofrontal, and occipital cortices. Schema therapy-based Young Schema Questionnaire (YSQ-S2) scores of early maladaptive schemas on emotional deprivation were linked to left medial temporal lobe gray matter reductions. CONCLUSIONS: Our results confirm orbitofrontal structural deficits in BPD, while providing a framework and preliminary findings on identifying structural correlates of symptom dimensions in BPD, especially with dorsolateral and orbitofrontal cortices.
Asunto(s)
Trastorno de Personalidad Limítrofe/patología , Trastorno de Personalidad Limítrofe/psicología , Encéfalo/patología , Adulto , Mapeo Encefálico , Emociones , Femenino , Lóbulo Frontal/patología , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Lóbulo Temporal/patologíaRESUMEN
BACKGROUND: Personality disorders (PD) belong to the most common and most serious mental disorders as regards social dysfunction, inability to work, occurrence of comorbidity and suicidal risk. PDs also crucially influence the incidence, clinical course and treatment response of mental disorders with high suicidal risk, such as depression or substance abuse. One key issue of PD concerns the regulation of emotions. METHODS: Both 1H-/31P-Chemical Shift Imaging (CSI) was applied in a single session to assess neurochemical markers of glutamate function (NAA, Glu) and local energy metabolism (PCr, ATP) in two patient cohorts encompassing 22 cluster B (CB) and 21 cluster C (CC) PD patients, whereby 10 patients of each group were on low-dose antidepressants, and in 60 healthy controls (HC). Non-parametric statistical tests and correlation analyses were performed to assess disease effects on the metabolites and their relation to symptomatology as assessed by SCL-90R self-ratings. RESULTS: Overall comparison including Bonferroni correction revealed significant differences of Glu across all groups in the dorsolateral prefrontal cortex (DLPFC). The following uncorrected results of pairwise tests were obtained: (i) Glu was bilaterally increased in the DLPFC in CB patients, whereas it was - together with NAA - bilaterally decreased in the DLPFC in CC patients and accompanied by increased PCr in the left DLPFC. (ii) NAA and Glu, accompanied by increased PCr, were significantly decreased in the dorsomedial prefrontal cortex (DMPFC) in CC patients. (iii) NAA was decreased in the right anterior cingulate cortex (ACC) in CB patients, and in the left ACC in CC patients with PCr being increased bilaterally. (iv) No associations were observed between metabolites and psychopathology measures. CONCLUSION: The observations in the DLPFC may reflect a neurobiochemical correlate of disturbed cognitive control function in CB and CC PD. While the alterations in CB patients suggest increased basal activity, the observed patterns in CC patients likely reflect decreased or inhibited activity. The alterations of NAA and Glu levels in the ACC and DMPFC indirectly support the assumption of disturbed neuronal function in regions involved in social cognition and mentalizing abilities in both CB and CC PD. Further studies should include the investigation of metabolites of neuronal inhibition (GABA) and the examination of treatment effects.
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Ácido Glutámico/metabolismo , Giro del Cíngulo/metabolismo , Trastornos de la Personalidad/diagnóstico por imagen , Trastornos de la Personalidad/patología , Adulto , Ácido Aspártico/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Corteza Prefrontal/patología , Adulto JovenRESUMEN
Impaired niacin sensitivity (NS) is one of the most replicated findings in untreated schizophrenia, and reflects a disturbance of prostaglandin-mediated pathways in association with deregulated arachidonic acid metabolism, pro-inflammatory activation, and vasomotor function. In ultra-high risk individuals (UHR) increased NS was reported recently, pointing towards dynamic alterations of the underlying pathomechanisms in the period preceding psychosis. However, these characteristics are still unresolved in the diverse UHR groups. We tested the hypothesis that NS is attenuated in patients who have transitioned to psychosis and in the Brief Limited Intermittent Psychotic Symptoms (BLIPS, UHR-B) and/or the attenuated symptoms (UHR-A) groups, while it is unchanged or increased in the genetic risk group (UHR-G). Sensitivity to three concentrations (0.1-0.001M) of aqueous methylnicotinate was tested in 84 UHR patients, 105 first-episode psychosis patients (FEP) and 180 healthy individuals (HC), using optical reflection spectroscopy (ORS). The UHR subgroup and transition/non-transition outcomes were assessed according to PACE criteria using the CAARMS. Psychopathology was assessed using SANS, SAPS, and BPRS or SCL-90-R self-ratings. In 0.001M data, decreased NS was found in the UHR-B (n=12), UHR-A (n=45) and the transition groups (n=13), similar to the result in FEP. NS in the UHR-G (n=27) and HC groups did not differ. In the UHR-B and FEP groups, NS and positive symptom scores were inversely correlated. These state marker properties could be used to characterize the intensity of the underlying pathomechanisms during the onset of psychosis or to identify UHR individuals that might benefit from related indicated prevention strategies.
Asunto(s)
Niacina/metabolismo , Síntomas Prodrómicos , Trastornos Psicóticos/diagnóstico , Piel/metabolismo , Análisis Espectral/métodos , Adolescente , Adulto , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Niacina/farmacología , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicología , Riesgo , Piel/efectos de los fármacos , Piel/patología , Factores de Tiempo , Adulto JovenRESUMEN
BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component.
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Envejecimiento Prematuro/patología , Envejecimiento/patología , Trastorno Bipolar/patología , Encéfalo/patología , Aprendizaje Automático , Esquizofrenia/patología , Adulto , Envejecimiento Prematuro/diagnóstico por imagen , Trastorno Bipolar/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/patología , Esquizofrenia/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Dimensional approaches in highly prevalent psychiatric disorders like depression or anxiety could lead to a better understanding of pathogenesis and advantages in early detection and prevention. In an effort to better understand associations of brain structural variation across the depression/anxiety spectra, we investigated minor subclinical symptoms in a non-clinical healthy population. METHODS: We studied 177 healthy subjects from the community, who underwent high-resolution T1-weighted 3T MRI and completed the symptom-checklist-90 (SCL-90-R). Using voxel-based morphometry (VBM) analysis with CAT12 software, we correlated SCL-90-R-subscales for depression, anxiety, and somatization with gray matter across the brain. RESULTS: Significant positive gray matter correlations emerged across all three scales in different areas: the depression subscale correlated positively with gray matter in the Rolandic operculum, superior temporal gyrus (left) and postcentral gyrus (bilateral), the anxiety subscale correlated positively with middle temporal gyrus, Rolandic operculum, middle cingular gyrus and precuneus bilaterally, and the somatization subscale with left inferior prefrontal cortex. Somatization also showed negative correlations with cerebellar vermis and right supplementary motor area. LIMITATIONS: Our study is limited to VBM and does not include surface-based measures. It also only contains subjects with very small psychological distress by partly overlapping symptoms. CONCLUSION: Our findings are consistent with a non-linear relationship between symptom severity and cortical volume in several brain areas involved in both emotion regulation as well as altered in clinically manifest depressive/anxiety disorders.
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Ansiedad/patología , Cerebelo/patología , Corteza Cerebral/patología , Depresión/patología , Sustancia Gris/patología , Voluntarios Sanos/psicología , Trastornos Somatomorfos/patología , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Síntomas Prodrómicos , Adulto JovenRESUMEN
Both schizophrenia and bipolar disorder show abnormalities of white matter, as seen in diffusion tensor imaging (DTI) analyses of major brain fibre bundles. While studies in each of the two conditions have indicated possible overlap in anatomical location, there are few direct comparisons between the disorders. Also, it is unclear whether phenotypically similar subgroups (e.g. patients with bipolar disorder and psychotic features) might share white matter pathologies or be rather similar. Using region-of-interest (ROI) analysis of white matter with diffusion tensor imaging (DTI) at 3 T, we analysed fractional anisotropy (FA), radial diffusivity (RD), and apparent diffusion coefficient (ADC) of the corpus callosum and cingulum bundle in 33 schizophrenia patients, 17 euthymic (previously psychotic) bipolar disorder patients, and 36 healthy controls. ANOVA analysis showed significant main effects of group for RD and ADC (both elevated in schizophrenia). Across the corpus callosum ROIs, there was not group effect on FA, but for RD (elevated in schizophrenia, lower in bipolar disorder) and ADC (higher in schizophrenia, intermediate in bipolar disorder). Our findings show similarities and difference (some gradual) across regions of the two major fibre tracts implicated in these disorders, which would be consistent with a neurobiological overlap of similar clinical phenotypes.
Asunto(s)
Trastorno Bipolar/patología , Cuerpo Calloso/patología , Imagen de Difusión Tensora/métodos , Esquizofrenia/patología , Sustancia Blanca/patología , Adulto , Trastorno Bipolar/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms.
Asunto(s)
Trastorno Bipolar/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Adulto , Trastorno Bipolar/fisiopatología , Femenino , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Lóbulo Parietal/fisiopatologíaRESUMEN
Hippocampal structural and functional integrity impacts on multiple remote areas of the brain, and this connectivity is central to multiple cognitive functions in healthy and disease. We studied associations of hippocampal metabolic markers N-acetyl aspartate (NAA) and glutamate (Glu and Glx; assessed with 1H magnetic resonance spectroscopy) and brain grey matter (studied with voxel-based morphometry, VBM) in 20 healthy subjects. We found a significant correlation between right hippocampal NAA and left ventrolateral prefrontal cortical grey matter (TFCE, p<0.05, FWE-corrected), as well as verbal fluency markers, and right hippocampal Glx (glutamate/glutamine) and left cerebellar volume. Our studies demonstrate a structure-function correlation that might underlie the interaction of the hippocampus with prefrontal cortex and cerebellum, which might be central to several neurological and psychiatric disorders, including schizophrenia or depression.
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Hipocampo/metabolismo , Imagen por Resonancia Magnética , Procesos Mentales , Corteza Prefrontal/diagnóstico por imagen , Espectroscopía de Protones por Resonancia Magnética , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Mezclas Complejas/metabolismo , Femenino , Lateralidad Funcional , Ácido Glutámico/metabolismo , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/metabolismo , Hipocampo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Corteza Prefrontal/metabolismo , Adulto JovenRESUMEN
Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.
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Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Trastornos Psicóticos/dietoterapia , Trastornos Psicóticos/inmunología , Adolescente , Adulto , Biomarcadores/sangre , Estudios Transversales , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Subunidad alfa del Receptor de Interleucina-2/sangre , Interleucina-6/sangre , Masculino , Aceptación de la Atención de Salud , Síntomas Prodrómicos , Trastornos Psicóticos/sangre , Trastornos Psicóticos/prevención & control , Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. METHODS: We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. RESULTS: Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. CONCLUSIONS: Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.
Asunto(s)
Niacina/metabolismo , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/metabolismo , Piel/metabolismo , Adolescente , Adulto , Activación Enzimática , Ácidos Grasos/metabolismo , Femenino , Rubor/inducido químicamente , Humanos , Espacio Intracelular/metabolismo , Masculino , Niacina/farmacología , Fosfolipasas A2/metabolismo , Trastornos Psicóticos/etiología , Riesgo , Piel/efectos de los fármacos , Piel/patología , Adulto JovenRESUMEN
Bipolar disorder and schizophrenia share phenotypic and genotypic features, but might differ in aspects of abnormal neurodevelopmental trajectories. We studied gyrification, a marker of early developmental pathology, in high-resolution MRI scans of 34 patients with schizophrenia, 17 euthymic bipolar I disorder patients with previous psychotic symptoms, and 34 matched healthy controls in order to test the hypothesis of overlapping and diverging prefrontal gyrification abnormalities. We applied a novel, validated method for measuring local gyrification in each vertex point of the reconstructed cortical surface. Psychotic bipolar I patients had higher gyrification in dorsal anterior and infragenual cingulate cortex compared to either schizophrenia or healthy controls, while schizophrenia patients had higher gyrification than controls in anterior medial (BA 10) and orbitofrontal areas, altogether indicating disease-specific alterations in the prefrontal cortex. Our findings indicate gyrification changes in a specific subgroup of bipolar I disorder to affect an area relevant to emotion regulation, and distinct from changes seen in schizophrenia.
Asunto(s)
Trastorno Bipolar/patología , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Corteza Prefrontal/patología , Esquizofrenia/patología , Adulto , Femenino , Humanos , MasculinoRESUMEN
We analysed T1-weighted MRI scans using voxel-based morphometry (VBM) and tract-based spatial statistics (TBBS) on diffusion tensor images (DTI) in narcissistic personality disorder (NaPD) patients and healthy controls. Grey matter deficits include right prefrontal and bilateral medial prefrontal/anterior cingulate cortices, and decreased fractional anisotropy in right frontal lobe white matter.