EEG alterations during treatment with olanzapine

The aim of this naturalistic observational study was to investigate EEG alterations in patients under olanzapine treatment with a special regard to olanzapine dose and plasma concentration. Twenty-two in-patients of a psychiatric university ward with the monodiagnosis of paranoid schizophrenia (ICD-10: F20.0), who received a monotherapy of olanzapine were included in this study. All patients had a normal alpha-EEG before drug therapy, and did not suffer from brain-organic dysfunctions, as verified by clinical examination and cMRI scans. EEG and olanzapine plasma levels were determined under steady-state conditions (between 18 and 22 days after begin of treatment). In 9 patients (40.9%), pathological EEG changes (one with spike-waves) consecutive to olanzapine treatment were observed. The dose of olanzapine was significantly higher in patients with changes of the EEG than in patients without changes (24.4 mg/day (SD: 8.1) vs. 12.7 mg/day (SD: 4.8); T = −4.3, df = 21, P < 0.001). In patients with EEG changes, the blood plasma concentration of olanzapine (45.6 μg/l (SD: 30.9) vs. 26.3 μg/l (SD: 21.6) tended to be also higher. The sensitivity of olanzapine dosage to predict EEG changes was 66.7%, the specificity 100% (Youden-index: 0.67). EEG abnormalities during olanzapine treatment are common. These are significantly dose dependent. Thus, EEG control recordings should be mandatory during olanzapine treatment with special emphasis on dosages exceeding 20 mg per day, although keeping in mind that EEGs have only a limited predictive power regarding future epileptic seizures

Amygdala Engagement in Response to Subthreshold Presentations of Anxious Face Stimuli in Adults with Autism Spectrum Disorders: Preliminary Insights

Current theoretical models of autism spectrum disorders (ASD) have proposed that impairments in the processing of social/emotional information may be linked to amygdala dysfunction. However, the extent to which amygdala functions are compromised in ASD has become a topic of debate in recent years. In a jittered functional magnetic resonance imaging study, sub-threshold presentations of anxious faces permitted an examination of amygdala recruitment in 12 high functioning adult males with ASD and 12 matched controls. We found heightened neural activation of the amygdala in both high functioning adults with ASD and matched controls. Neither the intensity nor the time-course of amygdala activation differed between the groups. However, the adults with ASD showed significantly lower levels of fusiform activation during the trials compared to controls. Our findings suggest that in ASD, the transmission of socially salient information along sub-cortical pathways is intact: and yet the signaling of this information to structures downstream may be impoverished, and the pathways that facilitate subsequent processing deficient

Widespread white matter microstructural differences in schizophrenia across 4322 individuals:Results from the ENIGMA Schizophrenia DTI Working Group

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Molecular Psychiatry advance online publication, 17 October 2017; doi:10.1038/mp.2017.170

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis

Data Availability Statement: The raw data supporting the conclusions of this article and code used for analysis will be made available by the authors on reasonable request pending appropriate study approvals and data transfer agreements between participating institutions.Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/brainsci14070669/s1, Table S1: Inclusion/exclusion criteria for each data source; Table S2: Deficit in words recalled for each clinical condition relative to matched controls. Refs. [61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100] are cited in the Supplementary Materials.Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.This research was funded by the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium (LIMBIC), Grant/Award Numbers: W81XWH18PH, TBIRPLIMBIC under Awards Numbers: W81XWH1920067 and W81XWH1320095; US Department of Defense, Grant/Award Number: AZ150145; US Department of Veterans Affairs, Grant/Award Numbers: I01 CX002097, I01 CX002096, I01 HX003155, I01 RX003444, I01 RX003443, I01 RX003442, I01 CX001135, I01 CX001246, I01 RX001774, I01 RX001135, I01 RX002076, I01 RX001880, I01 RX002172, I01 RX002173, I01 RX002171, I01 RX002174, I01 RX002170, 1I01 RX003444; National Institutes of Health (NIH), Grant/Award Number(s): RF1NS115268, RF1NS128961, U01NS086625, U01MH124639, P50MH115846, R01MH113827, R25MH080663, K08MH068540, R01NS100973, R01EB006841, P20GM103472, RO1MH083553, T32MH019535, R01 HD061504, RO1MH083553, R01AG050595, R01AG076838, R01AG060470, R01AG064955, P01AG055367, K23MH095661, R01MH094524, R01MH121246, T32MH019535, R01NS124585, R01NS122827, R61NS120249, R01NS122184, U54EB020403, R01MH116147, R56AG058854, P41EB015922, R01MH111671, P41RR14075, M01RR01066, R01EB006841, R01EB005846, R01 EB000840, RC1MH089257, U24 RR021992, and NCRR 5 month-RR001066 (MGH General Clinical Research Center); National Institute of Mental Health (NIMH), Grant/Award Number: 1P20RR021938; Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Grant/Award Numbers: PI15-00852, PI18-00945, JR19-00024, PI17-00481, PI20-00721; Sara Borrell contract, Grant/Award Number: CD19-00149; German Research Foundation DFG grant FOR2107, Grant/Award Numbers: JA 1890/7-1, JA 1890/7-2, NE2254/1-2, NE2254/2-1, NE2254/3-1, NE2254/4-1, KI588/14-1, KI588/14-2, DA1151/5-1, DA1151/5-2, SFB-TRR58, Projects C09 and Z02; European Union, NextGenerationEU, Grant/Award Numbers: PMP21/00051, PI19/01024; Structural Funds; Seventh Framework Program; H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking: Project PRISM-2, Grant/Award Number: 101034377; Project AIMS-2-TRIALS, Grant/Award Number: 777394; Horizon Europe; NSF, Grant/Award Number: 2112455; Madrid Regional Government, Grant/Award Number: B2017/BMD-3740 AGES-CM-2; Dalhousie Medical Research Foundation; Research Nova Scotia, Grant/Award Number: RNS-NHIG-2021-1931; NJ Commission on TBI Research Grants, Grant/Award Numbers: CBIR11PJT020, CBIR13IRG026; Department of Psychology, University of Oslo; Sunnaas Rehabilitation Hospital, Grant/Award Number: HF F32NS119285; Canadian Institutes of Health Research, Grant/Award Number: 166098; Neurological Foundation of New Zealand, Grant/Award Number: 2232 PRG; Canterbury Medical Research Foundation, University of Otago; Biogen US Investigator-initiated grant; Italian Ministry of Health, Grant/Award Number: RF-2019-12370182 and Ricerca Corrente RC 23; National Institute on Aging; National Health and Medical Research Council, Investigator Grant/Award Number: APP1176426; PA Health Research, Grant/Award Number: 4100077082; La Caixa Foundation, Grant/Award Number: 100010434, fellowship code: LCF/BQ/PR22/11920017; Research Council of Norway, Grant/Award Number: 248238; Health Research Council of New Zealand Sir Charles Hercus Early Career Development, Grant/Award Numbers: 17/039 and 14-440; Health Research Council of New Zealand, Grant/Award Numbers: 20/538 and 14/440; Research and Education Trust Pacific Radiology, Grant/Award Number: MRIJDA; South-Eastern Norway Regional Health Authority, Grant/Award Number: 2018076; Norwegian ExtraFoundation for Health and Rehabilitation, Grant/Award Numbers: 2015/FO5146; South-Eastern Norway Regional Health Authority, Grant/Award Number: 2015044; Stiftelsen K.G. Jebsen, Grant/Award Number: SKGJ MED-02; The Liaison Committee between Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU), Grant/Award Number: 2020/39645; National Health and Medical Research Council, Grant/Award Number: APP1020526; Brain Foundation; Wicking Trust; Collie Trust; Sidney and Fiona Myer Family Foundation; U.S. Army Medical Research and Materiel Command (USAMRMC), Grant/Award Number: 13129004; Department of Energy, Grant/Award Number: DE-FG02-99ER62764; Mind Research Network; National Association for Research in Schizophrenia and Affective Disorders, Young Investigator Award; Blowitz Ridgeway and Essel Foundations; Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster; NOW ZonMw TOP, Grant/Award Number: 91211021; UCLA Easton Clinic for Brain Health; UCLA Brain Injury Research Center; Stan and Patty Silver; Clinical and Translational Research Center, Grant/Award Numbers: UL1RR033176, UL1TR000124; Mount Sinai Institute for NeuroAIDS Disparities; VA Rehab SPIRE; CDMRP PRAP; VA RR&D, Grant/Award Number: IK2RX002922; Veski Fellowship; Femino Foundation grant; Fundación Familia Alonso; Fundación Alicia Koplowitz; CIBERSAM, Madrid Regional Government, Grant/Award Numbers: B2017/BMD-3740 AGES-CM-2, 2019R1C1C1002457, 21-BR-03-01, 2020M3E5D9079910, 21-BR-03-01; Deutsche Forschungsgemeinschaft (DFG), Grant/Award Numbers: NE2254/1-2, NE2254/2-1, NE2254/3-1, NE2254/4-1

Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors. Results in two affected infants.

We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease. Both patients presented with a salt-losing episode simulating adrenal insufficiency. In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism. Aldosterone receptors were normal in both patients when studied after the surgical correction of the obstruction