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ABSTRACT: To examine the structural integrity of the dorsolateral prefrontal-basal ganglia-thalamocortical circuit in people with the deficit form of schizophrenia.
A three-dimensional structural MRI sequence was used to conduct morphometric assessments of cortical and subcortical regions in deficit and nondeficit outpatients with schizophrenia and healthy controls.
The superior prefrontal and superior and middle temporal gyral gray matter volumes were significantly smaller in the deficit versus the nondeficit group and normal control groups. There were no significant group differences in examined subcortical structures.
People with deficit schizophrenia are characterized by selective reductions in the prefrontal and temporal cortex.
Biological Psychiatry 04/2012; 136(1-3):51-4. · 8.28 Impact Factor
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ABSTRACT: Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.
Journal of psychiatric research 03/2012; 46(3):394-401. · 3.72 Impact Factor
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David Fraguas,
Ana Gonzalez-Pinto,
Juan Antonio Micó,
Santiago Reig,
Mara Parellada,
Mónica Martínez-Cengotitabengoa,
Josefina Castro-Fornieles,
Marta Rapado-Castro,
Immaculada Baeza,
Joost Janssen,
Manuel Desco,
Juan Carlos Leza, Celso Arango
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ABSTRACT: Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.
Biological Psychiatry 02/2012; 137(1-3):58-65. · 8.28 Impact Factor
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ABSTRACT: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population.
Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004.
An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999).
Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.
The Journal of Clinical Psychiatry 12/2011; 72(12):1592-9. · 5.80 Impact Factor
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Stacy Steinberg,
Simone de Jong,
Ole A Andreassen,
Thomas Werge,
Anders D Børglum,
Ole Mors,
Preben B Mortensen,
Omar Gustafsson,
Javier Costas,
Olli P H Pietiläinen, [......],
Sarah Tosato,
Leena Peltonen,
Roel A Ophoff,
David A Collier,
David St Clair,
Marcella Rietschel,
Sven Cichon,
Hreinn Stefansson,
Dan Rujescu,
Kari Stefansson
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ABSTRACT: Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)).
Human Molecular Genetics 08/2011; 20(20):4076-81. · 7.64 Impact Factor
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Hreinn Stefansson,
Roel A Ophoff,
Stacy Steinberg,
Ole A Andreassen,
Sven Cichon,
Dan Rujescu,
Thomas Werge,
Olli P H Pietiläinen,
Ole Mors,
Preben B Mortensen, [......],
Hannes Petursson,
Markus M Nöthen,
Marcella Rietschel,
Paul M Matthews,
Pierandrea Muglia,
Leena Peltonen,
David St Clair,
David B Goldstein,
Kari Stefansson,
David A Collier
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ABSTRACT: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Nature 08/2009; 460(7256):744-7. · 36.28 Impact Factor
