Publications by authors named "Douglas S Lehrer"

Many controversies exist regarding vitamin D supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D intake above 4000-10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations.

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Article Synopsis
  • * Researchers discovered 287 genomic regions associated with schizophrenia, emphasizing genes specifically active in excitatory and inhibitory neurons, and identified 120 key genes potentially responsible for these associations.
  • * The findings highlight important biological processes related to neuronal function, suggesting overlaps between common and rare genetic variants in both schizophrenia and neurodevelopmental disorders, ultimately aiding future research on these conditions.
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Article Synopsis
  • A meta-analysis of whole exomes from 24,248 schizophrenia cases and 97,322 controls identified ultra-rare coding variants (URVs) linked to schizophrenia risk across 10 significant genes.
  • Some of these genes are heavily expressed in the brain and are involved in synapse formation, pointing to a connection between glutamate system dysfunction and schizophrenia.
  • Additionally, there's an overlap in rare variant risks shared with other disorders like autism and epilepsy, suggesting that both common and rare genetic factors contribute to the same biological processes underlying schizophrenia.
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Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (F-fluorodeoxyglucose and F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D/D receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia.

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Reading impairments are prominent trait-like features of cognitive deficits in schizophrenia, predictive of overall cognitive functioning and presumably linked to dopaminergic abnormalities. To evaluate this, we used F-fallypride PET in 19 healthy and 21 antipsychotic-naïve schizophrenia subjects and correlated dopamine receptor binding potentials in relevant AFNI-derived regions and voxelwise with group performance on WRAT4 single-word reading subtest. Healthy subjects' scores were positively and linearly associated with D/D receptor availability in the rectus, orbital and superior frontal gyri, fusiform and middle temporal gyri, as well as middle occipital gyrus and precuneus, all predominantly in the left hemisphere and previously implicated in reading, hence suggesting that higher dopamine receptor density is cognitively advantageous.

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Decreased fractional anisotropy and increased glucose utilization in the white matter have been reported in schizophrenia. These findings may be indicative of an inverse relationship between these measures of white matter integrity and metabolism. We used F-fluorodeoxyglucose positron emission tomography and diffusion-tensor imaging in 19 healthy and 25 schizophrenia subjects to assess and compare coterritorial correlation patterns between glucose utilization and fractional anisotropy on a voxel-by-voxel basis and across a range of automatically placed representative white matter regions of interest.

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Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent.

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Overlapping decreases in extrastriatal dopamine D/D-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental. To ascertain this, we used two consecutive F-fluorodeoxyglucose and F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects.

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Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.

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Vitamin D3 is a secosteroid hormone produced in the skin in amounts estimated up to 25,000 international units (IUs) a day by the action of UVB radiation on 7-dehydrocholesterol. Vitamin D deficiency is common due to both lack of adequate sun exposure to the skin, and because vitamin D is present in very few food sources. Deficiency is strongly linked to increased risk for a multitude of diseases, several of which have historically been shown to improve dramatically with either adequate UVB exposure to the skin, or to oral or topical supplementation with vitamin D.

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Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and F-fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D/D receptor density and white matter fractional anisotropy in each diagnostic group.

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WHODAS-2.0 is a suggested replacement to the GAF in DSM-5. This study's purpose was to assess their comparative correlation in adults with schizophrenia spectrum disorder.

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Tuberculosis remains an epidemic throughout the world, with over 2 billion people, or more than one third of the world's population, infected with TB. In 2015, there were an estimated 10.4 million new cases of tuberculosis, and 1.

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Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia.

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A schizophrenia phenotype for paternal and maternal age effects on illness risk could benefit etiological research. As odor sensitivity is associated with variability in symptoms and cognition in schizophrenia, we examined if it was related to parental ages in patients and healthy controls. We tested Leukocyte Telomere Length (LTL) as an explanatory factor, as LTL is associated with paternal age and schizophrenia risk.

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Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA.

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Objective: Poor insight is a cardinal symptom of schizophrenia that, while not universally and uniformly expressed in all patients, is among the most common of its manifestations. Available neurobiological and neurocognitive evidence linking the phenomenon to core pathophysiology of schizophrenia justifies extension of the anosognosia construct to schizophrenia-related insight deficits. Poor insight is a core attribute of schizophrenia, occurring in 57 to 98 percent of patients.

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The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository.

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Background: Molecular imaging of dopaminergic parameters has contributed to the dopamine hypothesis of schizophrenia, expanding our understanding of pathophysiology, clinical phenomenology and treatment. Our aim in this study was to compare (18)F-fallypride binding potential BP(ND) in a group of patients with schizophrenia-spectrum illness vs. controls, with a particular focus on the cortex and thalamus.

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This study asked whether latent class modeling methods and multiple ratings of the same cases might permit quantification of the accuracy of forensic assessments. Five evaluators examined 156 redacted court reports concerning criminal defendants who had undergone hospitalization for evaluation or restoration of their adjudicative competence. Evaluators rated each defendant's Dusky-defined competence to stand trial on a five-point scale as well as each defendant's understanding of, appreciation of, and reasoning about criminal proceedings.

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Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder.

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Background: Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities.

Methods: Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug naïve schizophrenics (10 men, 5 women, mean age 28.

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We used the highly selective D2/D3 dopamine PET radioligand [F-18]fallypride to demonstrate that cognitive task induced dopamine release can be measured in the extrastriatal region of the thalamus, a region containing 10-fold fewer D2 dopamine receptors than the striatum. Human studies were acquired on 8 healthy volunteers using a single [F-18]fallypride injection PET imaging session. A spatial attention task, previously demonstrated to increase FDG uptake in the thalamus, was initiated following a period of radioligand uptake.

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Objective: Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit.

Method: Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained.

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