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1.
Curr Top Behav Neurosci ; 44: 161-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30828767

RESUMO

Clinical and pre-clinical studies have demonstrated an important role of neuroinflammation in the etiology of schizophrenia. While the underlying mechanisms remain poorly understood, there are some studies demonstrating an association between maternal immune activation and behavioral changes in adult offspring and identifying early life infection as a trigger for schizophrenia; in addition, inflammatory markers were found to be increased in the schizophrenic post-mortem brain. During maternal immune activation, pro-inflammatory mediators such as cytokines, chemokines, antibodies, and acute-phase proteins are released in the maternal bloodstream, thus increasing the permeability of the placental barrier and the fetal blood-brain barrier, allowing the inflammatory mediators to enter the fetal brain. In the central nervous system (CNS), these pro-inflammatory mediators are able to activate microglial cells that can release pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6. As a consequence, circulating immune cells may infiltrate the brain, increasing cytokine levels and releasing antibodies that aggravate the neuroinflammation. Neuroinflammation may affect processes that are pivotal for normal brain maturation such as myelination, synaptic pruning, and neuronal remodeling. Microglial cell activation and pro-inflammatory mediators have been extensively studied in schizophrenic post-mortem brain samples. Some results of these investigations demonstrated an increase in microglial activation markers, cytokines, and chemokines in post-mortem brain samples from individuals with schizophrenia. In contrast, there are studies that have demonstrated low levels of microglial activation makers in the schizophrenic post-mortem brain. Thus, based on the important role of neuroinflammation as a trigger in the development of schizophrenia, this chapter aims (1) to enumerate evidence of neuroinflammation and microglial activation from pre-clinical schizophrenia models, (2) to show links between schizophrenia and neuroinflammation in clinical studies, and (3) to identify mechanisms by which microglial activation may influence in the development of schizophrenia.


Assuntos
Microglia , Transtornos Psicóticos , Esquizofrenia , Encéfalo/imunologia , Encéfalo/patologia , Citocinas , Feminino , Humanos , Microglia/imunologia , Gravidez , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/patologia , Esquizofrenia/imunologia , Esquizofrenia/patologia
2.
Indian J Med Res ; 149(4): 489-496, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411172

RESUMO

Background & objectives: Substance use disorders are a major public health concern in Punjab. However, reliable estimates of prevalence of substance use disorders are not available for the State. The present study reports estimates of prevalence of substance use disorders in Punjab, conducted as part of National Mental Health Survey, India. Methods: Using multistage stratified random cluster sampling, 2895 individuals from 719 households of 60 clusters (from 4 districts of Punjab) were interviewed. Mini International Neuropsychiatric Interview and Fagerstrom nicotine dependence scale were used to assess substance use disorders. Results: The sample comprised almost equal numbers of males and females. Nearly 80 per cent had less than or equal to high school education, and 70 per cent were married. The weighted prevalence of alcohol and other substance use disorders was 7.9 and 2.48 per cent, respectively. The prevalence of tobacco dependence was 5.5 per cent; 35 per cent households had one person with substance use disorder. The prevalence was highest in the productive age group (30-39 yr), urban metro and less educated persons. The prevalence of alcohol and other substance use disorders was much higher in Punjab as compared to other States where survey was done. Tobacco dependence was lowest in Punjab. Majority (87%) of the persons with substance use disorders did not suffer from any other mental disorder. Treatment gap was 80 per cent. Interpretation & conclusions: Punjab has a high burden of substance use disorders. The estimates will help clinicians and policymakers to plan the strategies against the menace of substance use disorders effectively.


Assuntos
Transtornos Mentais/epidemiologia , Transtornos Psicóticos/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tabagismo/epidemiologia , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Masculino , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Transtornos Psicóticos/patologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Inquéritos e Questionários , Tabagismo/patologia , Adulto Jovem
3.
Am J Psychiatry ; 176(7): 564-572, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31164007

RESUMO

OBJECTIVE: The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures. METHODS: Choroid plexus volume was quantified (using FreeSurfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects. RESULTS: Choroid plexus volume was significantly larger in probands compared with first-degree relatives or healthy control subjects; first-degree relatives had intermediate enlargement compared with healthy control subjects; and total choroid plexus volume was significantly heritable. Larger volume was associated with worse cognition, smaller total gray matter and amygdala volume, larger lateral ventricle volume, and lower structural connectivity in probands. Associations between larger volume and higher levels of interleukin 6 in probands was also observed. CONCLUSIONS: These findings suggest the involvement of the choroid plexus across the psychosis spectrum with a potential pathophysiological mechanism involving the neuroimmune axis, which functions in maintaining brain homeostasis and interacting with the peripheral immune and inflammatory system. The choroid plexus may be an important target in future research.


Assuntos
Plexo Corióideo/patologia , Cognição , Inflamação/patologia , Transtornos Psicóticos/patologia , Adulto , Estudos de Casos e Controles , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/fisiopatologia , Cognição/fisiologia , Feminino , Humanos , Inflamação/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Tamanho do Órgão , Fenótipo , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia
4.
Eur J Med Genet ; 62(8): 103705, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229682

RESUMO

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a hemizygous microdeletion on the long arm of chromosome 22 and is associated with a high risk for psychosis and cognitive impairment. One of the genes located in the deleted region of 22q11DS is Proline Dehydrogenase (PRODH) which is important for conversion of proline to glutamate. Glutamate is the primary excitatory neurotransmitter and is involved in the pathophysiology of psychosis as well as in cognition. Excessive concentrations are toxic. Possibly, neuroprotective drugs modulating glutamatergic neurotransmission could be effective in treating psychotic symptoms and cognitive enhancement in patients with 22q11DS. Riluzole is a potent anti-glutamatergic drug that reduces glutamatergic neurotransmission. Here we report acute (single dose) and long-term effects of riluzole on glutamate and GABA levels in the anterior cingulate cortex (ACC) and striatum (measured with magnetic resonance spectroscopy, 1H-MRS) as well as on psychotic symptoms and cognitive functioning in a medication-free 23-year old woman with 22q11DS. Patient presented with frequent auditory and visual hallucinations and mild paranoid ideas. The 1H-MRS measurements showed that after a single dose riluzole (50 mg), glutamate in the ACC and striatum was reduced whereas striatal GABA increased compared to baseline. Strikingly, hallucinations and paranoia disappeared. Therefore, riluzole treatment was initiated and patient was followed up after 18 months of treatment. At follow-up, patient reported no hallucinations or paranoia and several cognitive functions were improved. Furthermore, glutamate concentrations in the ACC and striatum decreased whereas GABA concentrations increased in the striatum but decreased in the ACC. These results suggests that riluzole may be an effective treatment option for psychotic symptoms and cognitive enhancement in 22q11DS. Results warrant replication in a bigger sample.


Assuntos
Síndrome de DiGeorge/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Riluzol/administração & dosagem , Adulto , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/patologia , Feminino , Ácido Glutâmico/metabolismo , Humanos , Prolina/metabolismo , Prolina Oxidase/genética , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia , Adulto Jovem
5.
Psychiatry Res Neuroimaging ; 289: 26-36, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31132567

RESUMO

There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.


Assuntos
Córtex Cerebral/patologia , Transtornos Psicóticos/patologia , Substância Branca/patologia , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Risco , Substância Branca/diagnóstico por imagem , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-31054647

RESUMO

BACKGROUND: Gyrification features reflect brain development in the early prenatal environment. Clarifying the nature of these features in psychosis can help shed light on the role of early developmental insult. However, the literature is currently widely discrepant, which may reflect confounds related to formally psychotic patient populations or overreliance on a single feature of cortical surface morphometry (CSM). METHODS: This study compares CSM features of gyrification in clinical high-risk (n = 43) youths during the prodromal risk period to typically developing control subjects over two time points across three metrics: local gyrification index, mean curvature index, and sulcal depth (improving resolution and examination of change over 1 year). RESULTS: Gyrification was stable over time, supporting the idea that gyrification reflects early insult rather than abnormal development or reorganization associated with the disease state. Each of the indices highlighted unique, aberrant features in the clinical high-risk group with respect to control subjects. Specifically, the local gyrification index reflected hypogyrification in the lateral orbitofrontal cortex, superior bank of the superior temporal sulcus, anterior isthmus of the cingulate gyrus, and temporal poles; the mean curvature index indicated sharper gyral and flatter or wider sulcal peaks in the cingulate, postcentral, and lingual gyrus; sulcal depth identified shallow features in the parietal, superior temporal sulcus, and cingulate regions. Further, both the mean curvature index and sulcal depth converged on abnormal features in the parietal cortex. CONCLUSIONS: Gyrification metrics suggest early developmental insult and provide support for neurodevelopmental hypotheses. Observations of stable CSM features across time provide context for interpreting extant studies and speak to CSM as a promising stable marker and/or endophenotype. Collectively, findings support the importance of considering multiple CSM features.


Assuntos
Córtex Cerebral/patologia , Transtornos Psicóticos/patologia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Psicóticos/diagnóstico por imagem
7.
Lupus ; 28(5): 685-694, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018814

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an important cause of morbidity and mortality. We undertook this observational retrospective study of patients with NPSLE who had brain magnetic resonance imaging (MRI) to determine the indications for MRI and the correlation of clinical and laboratory findings with MRI. We identified 83 NPSLE patients (84.3% women) seen at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, between June 2003 and May 2017. The mean age at SLE diagnosis was 26.24 ± 12.81 years and the median interval to NPSLE was 11.0 (interquartile range, 4.0-39.0) months. The most common indications for MRI were seizures (45.8%), psychosis (18.1%) and cerebrovascular disease (18.1%). The MRI was abnormal in 68 (81.9%) with small-vessel disease in 65 (78.3%) and large-vessel disease in eight (9.6%). The small-vessel abnormalities were white-matter hyperintensities (WMH) (59.0%), atrophy (55.4%) and lacunae (4.6%). Our patients had high disease activity at NPSLE. Cerebrovascular disease was associated with an abnormal MRI ( p = 0.018) and large-vessel disease ( p = 0.014) on MRI. Our NPSLE patients were younger and had high disease activity, and seizures were more common compared with other studies. The most common MRI abnormalities were WMH and cortical atrophy, in agreement with other studies.


Assuntos
Encéfalo/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Adolescente , Adulto , Atrofia , Encéfalo/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imagem por Ressonância Magnética , Masculino , Fenótipo , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/patologia , África do Sul , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-30852127

RESUMO

BACKGROUND: A longer duration of untreated psychosis (DUP) has been linked with poor clinical outcomes and variation in resting-state striatal connectivity with central executive regions. However, the link between DUP and task-based activation of executive neurocognition has not previously been examined. This functional magnetic resonance imaging study examined the association between DUP and both activation and frontostriatal functional connectivity during a visual working memory (WM) paradigm in patients with first-episode psychosis. METHODS: Patients with first-episode psychosis (n = 37) underwent functional magnetic resonance imaging scanning while performing a visual WM task. At the single-subject level, task conditions were modeled; at the group level, each condition was examined along with DUP. Activation was examined within the dorsolateral prefrontal cortex, a primary region supporting visual WM activation. Frontostriatal functional connectivity during the WM was examined via psychophysical interaction between the dorsal caudate and the dorsolateral prefrontal cortex. Results were compared with a reference range of connectivity values in a matched group of healthy volunteers (n = 25). Task performance was also examined in relation to neuroimaging findings. RESULTS: No significant association was observed between DUP and WM activation. Longer DUP showed less functional frontostriatal connectivity with the maintenance of increasing WM load. Results were not related to task performance measures, consistent with previous work. CONCLUSIONS: Our data suggest that DUP may affect frontostriatal circuitry that supports executive functioning. Future work is necessary to examine if these findings contribute to the mechanism underlying the relationship between DUP and worsened clinical outcomes.


Assuntos
Antipsicóticos/uso terapêutico , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/patologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/patologia , Tempo para o Tratamento , Adolescente , Adulto , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos Psicóticos/diagnóstico por imagem , Adulto Jovem
9.
Psychiatry Res ; 274: 391-394, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30901624

RESUMO

We investigated the role of DGCR2, a corticogenesis-related gene, on schizophrenia (SZ) and its subphenotypes, including brain morphology. A total of 221 SZ patients, 263 controls and 70 antipsychotic-naïve first episode of psychosis (FEP) were genotyped for 17 DGCR2 polymorphisms. While no association between DGCR2 polymorphisms and SZ was found, the missense variant rs2072123 was associated to left rostral anterior cingulate thickness, showing that DGCR2 seems not to be associated directly with the SZ but might be influencing the brain morphology. We also showed a DGCR2 downregulation in SZ patients when compared to controls and FEP.


Assuntos
Giro do Cíngulo/patologia , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Esquizofrenia/genética , Esquizofrenia/patologia , Adulto , Feminino , Genótipo , Humanos , Masculino , Mutação de Sentido Incorreto , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-30745004

RESUMO

BACKGROUND: Psychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examined whether regional white matter (WM) development is disrupted in youths with psychosis spectrum (PS) features and whether WM maturation mediates the relationship between age and cognition in typically developing (TD) youths and youths with PS features. METHODS: We examined WM microstructure, as assessed via diffusion tensor imaging, in 670 individuals (age 10-22 years; 499 TD group, 171 PS group) by using tract-based spatial statistics. Multiple regressions were used to evaluate age × group interactions on regional WM indices. Mediation analyses were conducted on four cognitive domains-executive control, complex cognition, episodic memory, and social cognition-using a bootstrapping approach. RESULTS: There were age × group interactions on fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and retrolenticular internal capsule. Follow-up analyses revealed these effects were significant in both hemispheres. Bilateral SLF FA mediated the relationship between age and complex cognition in the TD group, but not the PS group. Regional FA did not mediate the age-associated increase in any of the other cognitive domains. CONCLUSIONS: Our results showed aberrant age-related effects in SLF and retrolenticular internal capsule FA in youths with PS features. SLF development supports emergence of specific higher-order cognitive functions in TD youths, but not in youths with PS features. Future mechanistic explanations for these relationships could facilitate development of earlier and refined targets for therapeutic interventions.


Assuntos
Encéfalo/patologia , Cognição/fisiologia , Transtornos Psicóticos/patologia , Substância Branca/patologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Criança , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Adulto Jovem
11.
Neuropsychopharmacology ; 44(6): 1055-1061, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30795003

RESUMO

Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) is lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 deep layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 deep layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs (combined cohort) that included all subjects from cohort 1 and two previously studied cohorts. Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or normal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.


Assuntos
Córtex Auditivo/patologia , Espinhas Dendríticas/patologia , Proteínas Associadas aos Microtúbulos , Transtornos Psicóticos/patologia , Células Piramidais/patologia , Esquizofrenia/patologia , Adulto , Córtex Auditivo/citologia , Córtex Auditivo/diagnóstico por imagem , Autopsia , Estudos de Casos e Controles , Contagem de Células , Estudos de Coortes , Espinhas Dendríticas/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem , Células Piramidais/ultraestrutura , Esquizofrenia/diagnóstico por imagem
12.
Biol Psychiatry ; 85(1): 79-87, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30122287

RESUMO

BACKGROUND: Elevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore, it is unknown whether antipsychotic efficacy is linked to reductions in dopamine synthesis capacity. We conducted a prospective [18F]-dihydroxyphenyl-L-alanine positron emission tomography study in antipsychotic naïve/free people with first-episode psychosis commencing antipsychotic treatment. METHODS: Dopamine synthesis capacity (indexed as influx rate constant) and clinical symptoms (measured using Positive and Negative Syndrome Scale) were measured before and after at least 5 weeks of antipsychotic treatment in people with first-episode psychosis. Data from a prior study indicated that a sample size of 13 would have >80% power to detect a statistically significant change in dopamine synthesis capacity at alpha = .05 (two tailed). RESULTS: A total of 20 people took part in the study, 17 of whom were concordant with antipsychotic medication at therapeutic doses. There was no significant effect of treatment on dopamine synthesis capacity in the whole striatum (p = .47), thalamus, or midbrain, nor was there any significant relationship between change in dopamine synthesis capacity and change in positive (ρ = .35, p = .13), negative, or total psychotic symptoms. CONCLUSIONS: Dopamine synthesis capacity is unaltered by antipsychotic treatment, and therapeutic effects are not mediated by changes in this aspect of dopaminergic function.


Assuntos
Antipsicóticos/uso terapêutico , Corpo Estriado/metabolismo , Dopamina/biossíntese , Neostriado/metabolismo , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/metabolismo , Adulto , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Masculino , Neostriado/diagnóstico por imagem , Neostriado/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Transtornos Psicóticos/patologia , Adulto Jovem
13.
Neuropsychopharmacology ; 44(5): 869-875, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30127342

RESUMO

Despite an increasing focus on transdiagnostic approaches to mental health, it remains unclear whether different diagnostic categories share a common neuronatomical basis. The current investigation sought to investigate whether a transdiagnostic set of structural alterations characterized schizophrenia, depression, post-traumatic stress disorder, and obsessive-compulsive disorder, and determine whether any such alterations reflected markers of psychiatric illness or pre-existing familial vulnerability. A total of 404 patients with a psychiatric diagnosis were recruited (psychosis, n = 129; unipolar depression, n = 92; post-traumatic stress disorder, n = 91; obsessive-compulsive disorder, n = 92) alongside n = 201 healthy controls and n = 20 unaffected first-degree relatives. We collected structural magnetic resonance imaging scans from each participant, and tested for transdiagnostic alterations using Voxel-based morphometry. Inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. The four psychiatric groups relative to healthy controls were all characterized by significantly greater gray matter volume in the putamen (right: z-score: 5.97, p-value < 0.001; left: z-score: 4.97, p-value = 0.001); the volume of this region was positively correlated with severity of symptoms across groups (r = 0.313; p < 0.001). Putamen enlargement was also evident in unaffected relatives compared to healthy controls (right: z-score: 8.13, p-value < 0.001; left: z-score: 9.38, p-value < 0.001). Taken collectively, these findings indicate that increased putamen volume may reflect a transdiagnostic marker of familial vulnerability to psychopathology. This is consistent with emerging conceptualizations of psychiatric illness, in which each disorder is understood as a combination of diagnosis-specific features and a transdiagnostic factor reflecting general psychopathology.


Assuntos
Transtorno Depressivo Maior/patologia , Substância Cinzenta/patologia , Transtorno Obsessivo-Compulsivo/patologia , Transtornos Psicóticos/patologia , Putamen/patologia , Transtornos de Estresse Pós-Traumáticos/patologia , Adulto , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Suscetibilidade a Doenças , Família , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Putamen/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
14.
Clin EEG Neurosci ; 50(1): 13-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29914267

RESUMO

OBJECTIVES: Although schizencephaly belongs to the class of neurodevelopmental disorders, which are a well-known predisposing factor for psychosis, there is a lack of relevant studies and diagnostic guidelines on this relationship. METHOD: A case report of first-episode psychosis with persistent negative symptoms associated with schizencephaly is described and compared with 7 other cases found in the literature. RESULTS: We found perinatal pathology, cognitive deficit, and EEG abnormality in a patient with atypical initial symptoms of psychosis such as olfactory hallucinations. Abnormal EEG findings (left frontal spikes and frontal intermittent rhythmic delta activity) called for magnetic resonance imaging, which revealed left parieto-occipital closed-lip schizencephaly. The patient exhibited a partial response to low-dose amisulpride treatment. CONCLUSION: We conclude that schizencephaly in our patient was at first asymptomatic and later developed into clinically manifest schizophrenia-like disorder. Both magnetic resonance imaging and EEG were essential tools for establishing this diagnosis.


Assuntos
Encéfalo/fisiopatologia , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Esquizencefalia/fisiopatologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Adulto , Eletroencefalografia , Humanos , Masculino , Fenótipo , Transtornos Psicóticos/complicações , Esquizencefalia/complicações , Esquizofrenia/complicações
15.
Neuroimage Clin ; 21: 101624, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30528960

RESUMO

BACKGROUND: Findings from neurodevelopmental studies indicate that adolescents with psychosis spectrum disorders have delayed neurocognitive performance relative to the maturational state of their healthy peers. Using machine learning, we generated a model of neurocognitive age in healthy adults and investigated whether individuals in clinical high risk (CHR) for psychosis showed systematic neurocognitive age deviations that were accompanied by specific structural brain alterations. METHODS: First, a Support Vector Regression-based age prediction model was trained and cross-validated on the neurocognitive data of 36 healthy controls (HC). This produced Cognitive Age Gap Estimates (CogAGE) that measured each participant's deviation from the normal cognitive maturation as the difference between estimated neurocognitive and chronological age. Second, we employed voxel-based morphometry to explore the neuroanatomical gray and white matter correlates of CogAGE in HC, in CHR individuals with early (CHR-E) and late (CHR-L) high risk states. RESULTS: The age prediction model estimated age in HC subjects with a mean absolute error of ±2.2 years (SD = 3.3; R2 = 0.33, P < .001). Mean (SD) CogAGE measured +4.3 (8.1) years in CHR individuals compared to HC (-0.1 (5.5) years, P = .006). CHR-L individuals differed significantly from HC subjects while this was not the case for the CHR-E group. CogAGE was associated with a distributed bilateral pattern of increased GM volume in the temporal and frontal areas and diffuse pattern of WM reductions. CONCLUSION: Although the generalizability of our findings might be limited due to the relatively small number of participants, CHR individuals exhibit a disturbed neurocognitive development as compared to healthy peers, which may be independent of conversion to psychosis and paralleled by an altered structural maturation process.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Transtornos Psicóticos/patologia , Transtornos Psicóticos/psicologia , Adulto , Fatores Etários , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Modelos Neurológicos , Testes Neuropsicológicos , Transtornos Psicóticos/diagnóstico por imagem , Fatores de Risco , Máquina de Vetores de Suporte , Adulto Jovem
16.
Qual Life Res ; 28(3): 703-712, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30328009

RESUMO

PURPOSE: The purpose of the study was to test whether elevated levels of depressive and anxiety symptoms affect parent-proxy reports of health-related quality of life (HRQL) of children with mental disorder. METHODS: A sample of 114 children, who screened positive for mental disorder using the Mini International Neuropsychiatric Interview were studied. Parents' depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale (CES-D) and anxiety symptoms using the State Trait Anxiety Inventory (STAI). To examine whether parental psychopathology moderated their reports of child HRQL (using the KIDSCREEN-27), a series of multiple regression analyses with product-term interactions were conducted. RESULTS: Significant interactions were found for the moderating effect of parental depressive [ß = 0.025 (0.007, 0.042)] and anxiety symptoms [ß = 0.033 (0.011, 0.054)] on the domain of child social support and peers relations, as well as for the moderating effect of parental levels of depression on parent proxy child physical well-being [ß = - 0.017 (- 0.031, - 0.003)]. Parents with elevated levels of depressive or anxiety symptoms reported lower scores for those domains of child HRQL. CONCLUSIONS: Symptoms of depression and anxiety in parents influence their reports of the HRQL of their children with mental disorder, particularly in the areas of physical well-being and social support and peers. Given the importance of patient-reported outcomes in the assessment and monitoring of children with chronic conditions, including HRQL, health professionals caring for children with mental disorder should be aware of how parental psychopathology contributes to informant bias. Future research examining why psychopathology influences parental reports of child HRQL is warranted.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Pais/psicologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Qualidade de Vida/psicologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Procurador , Transtornos Psicóticos/patologia
17.
Schizophr Bull ; 45(1): 222-232, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29474680

RESUMO

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness.


Assuntos
Cromossomos Humanos Par 6/genética , Predisposição Genética para Doença/genética , Substância Cinzenta/patologia , Lobo Parietal/patologia , Córtex Pré-Frontal/patologia , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia , Esquizofrenia/genética , Esquizofrenia/patologia , Adolescente , Adulto , Feminino , Estudos de Associação Genética , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Parietal/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos Psicóticos/diagnóstico por imagem , Risco , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
18.
Eur Arch Psychiatry Clin Neurosci ; 269(4): 397-406, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29572660

RESUMO

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis.


Assuntos
Córtex Pré-Frontal/patologia , Sintomas Prodrômicos , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Adolescente , Adulto , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Transtornos Psicóticos/diagnóstico por imagem , Risco , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
19.
Schizophr Bull ; 45(1): 169-179, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29385604

RESUMO

Background: Psychotic experiences (PEs) are considered part of an extended psychosis phenotype and are associated with an elevated risk of developing a psychotic disorder. Risk of transition increases with persistence of PEs, and this is thought to be modulated by genetic and environmental factors. However, it is unclear if persistence is associated with progressive schizophrenia-like changes in neuroanatomy. Methods: We examined cortical morphometry using MRI in 247 young adults, from a population-based cohort, assessed for the presence of PEs at ages 18 and 20. We then incorporated a polygenic risk score for schizophrenia (PRS) to elucidate the effects of high genetic risk. Finally, we used atlas-based tractography data to examine the underlying white matter. Results: Individuals with persisting PEs showed reductions in gyrification (local gyrification index: lGI) in the left temporal gyrus as well as atypical associations with brain volume (TBV) in the left occipital and right prefrontal gyri. No main effect was found for the PRS, but interaction effects with PEs were identified in the orbitofrontal, parietal, and temporal regions. Examination of underlying white matter did not provide strong evidence of further disturbances. Conclusions: Disturbances in lGI were similar to schizophrenia but findings were mostly limited to those with persistent PEs. These could reflect subtle changes that worsen with impending psychosis or reflect an early vulnerability associated with the persistence of PEs. The lack of clear differences in underlying white matter suggests our findings reflect early disturbances in cortical expansion rather than progressive changes in brain structure.


Assuntos
Córtex Cerebral/patologia , Predisposição Genética para Doença/genética , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia , Esquizofrenia/genética , Esquizofrenia/patologia , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Estudos de Coortes , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Herança Multifatorial , Transtornos Psicóticos/diagnóstico por imagem , Risco , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
20.
Early Interv Psychiatry ; 13(4): 848-852, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29770569

RESUMO

AIM: Impulsive behaviours, which are frequent in young people suffering from psychosis have been linked to risky and violent behaviours and participate to the burden of psychotic illness. Given that morphological brain correlates of impulsivity in schizophrenia have been poorly investigated especially in young adults, the aim of this study was to investigate the relationship between impulsivity and cortical thickness in early psychosis (EP) patients. METHOD: A total of 17 male subjects in the early phase of psychosis were recruited. Impulsivity was assessed with the Lecrubier Impulsivity Rating Scale. Mean cortical thickness was extracted from magnetic resonance imaging brain scans, using surface-based methods. RESULTS: Mean cortical thickness in the frontal lobe correlated positively with mean impulsivity in EP male patients. CONCLUSION: Our results suggest that psychotic subjects exhibiting higher impulsivity have larger frontal cortical thickness, which may pave the way towards the identification of patients with a higher risk to display impulsive behaviours.


Assuntos
Lobo Frontal/patologia , Comportamento Impulsivo , Transtornos Psicóticos/patologia , Transtornos Psicóticos/psicologia , Humanos , Hipertrofia/patologia , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Adulto Jovem
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