scholarly journals Baseline measures of cerebral glutamate and GABA levels in individuals at ultrahigh risk for psychosis: Implications for clinical outcome after 12 months

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
C. Wenneberg ◽  
B. Y. Glenthøj ◽  
L. B. Glenthøj ◽  
B. Fagerlund ◽  
K. Krakauer ◽  
...  

Abstract Background. Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. Methods. About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. Results. There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = −0.34, N = 51, p = 0.01) in an explorative analysis. Conclusions. The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1272
Author(s):  
Amira Bryll ◽  
Wirginia Krzyściak ◽  
Paulina Karcz ◽  
Natalia Śmierciak ◽  
Tamas Kozicz ◽  
...  

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.


2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
Author(s):  
Kirsten B. Bojesen ◽  
Bjørn H. Ebdrup ◽  
Kasper Jessen ◽  
Anne Sigvard ◽  
Karen Tangmose ◽  
...  

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.


2013 ◽  
Vol 146 (1-3) ◽  
pp. 231-237 ◽  
Author(s):  
Chieh-Hsin Lin ◽  
Chieh-Liang Huang ◽  
Yue-Cune Chang ◽  
Po-Wei Chen ◽  
Chun-Yuan Lin ◽  
...  

2017 ◽  
Vol 43 (3-4) ◽  
pp. 117-123 ◽  
Author(s):  
Vanessa D. Beuscher ◽  
Joji B. Kuramatsu ◽  
Stefan T. Gerner ◽  
Julia Köhn ◽  
Hannes Lücking ◽  
...  

Background and Purpose: Hemispheric location might influence outcome after intracerebral hemorrhage (ICH). INTERACT suggested higher short-term mortality in right hemispheric ICH, yet statistical imbalances were not addressed. This study aimed at determining the differences in long-term functional outcome in patients with right- vs. left-sided ICH with a priori-defined sub-analysis of lobar vs. deep bleedings. Methods: Data from a prospective hospital registry were analyzed including patients with ICH admitted between January 2006 and August 2014. Data were retrieved from institutional databases. Outcome was assessed using the modified Rankin Scale (mRS) score. Outcome measures (long-term mortality and functional outcome at 12 months) were correlated with ICH location and hemisphere, and the imbalances of baseline characteristics were addressed by propensity score matching. Results: A total of 831 patients with supratentorial ICH (429 left and 402 right) were analyzed. Regarding clinical baseline characteristics in the unadjusted overall cohort, there were differences in disfavor of right-sided ICH (antiplatelets: 25.2% in left ICH vs. 34.3% in right ICH; p < 0.01; previous ischemic stroke: 14.7% in left ICH vs. 19.7% in right ICH; p = 0.057; and presence/extent of intraventricular hemorrhage: 45.0% in left ICH vs. 53.0% in right ICH; p = 0.021; Graeb-score: 0 [0-4] in left ICH vs. 1 [0-5] in right ICH; p = 0.017). While there were no differences in mortality and in the proportion of patients with favorable vs. unfavorable outcome (mRS 0-3: 142/375 [37.9%] in left ICH vs. 117/362 [32.3%] in right ICH; p = 0.115), patients with left-sided ICH showed excellent outcome more frequently (mRS 0-1: 64/375 [17.1%] in left ICH vs. 43/362 [11.9%] in right ICH; p = 0.046) in the unadjusted analysis. After adjusting for confounding variables, a well-balanced group of patients (n = 360/hemisphere) was compared showing no differences in long-term functional outcome (mRS 0-3: 36.4% in left ICH vs. 33.9% in right ICH; p = 0.51). Sub-analyses of patients with deep vs. lobar ICH revealed also no differences in outcome measures (mRS 0-3: 53/151 [35.1%] in left deep ICH vs. 53/165 [32.1%] in right deep ICH; p = 0.58). Conclusion: Previously described differences in clinical end points among patients with left- vs. right-hemispheric ICH may be driven by different baseline characteristics rather than by functional deficits emerging from different hemispheric functions affected. After statistical corrections for confounding variables, there was no impact of hemispheric location on functional outcome after ICH.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Miguel A Barboza ◽  
Rodrigo Uribe ◽  
Fabiola Serrano ◽  
Luis C Becerra-Pedraza ◽  
D. K Mantilla-Barbosa ◽  
...  

Background and purpose: Atherosclerotic ischemic stroke is the second most frequent etiology of stroke in the adult population. Functional outcome, mortality and recurrence of stroke rates on the long-term follow-up are poorly studied. This study investigates long-term outcome among patients with ischemic stroke secondary to atherosclerotic causality, and identifies the main factors associated with poor outcome, recurrence, and death. Methods: We analyzed data from our consecutive acute ischemic stroke database, over a period of 25 years (1990-2015). The endpoints were: bad outcome (Modified Rankin Score ≥3), recurrence and mortality at discharge, and final follow-up. Multivariate Cox and Kaplan-Meier analysis were used to estimate the probability of death and recurrence. Results: A total of 946 consecutive atherosclerotic stroke patients were included (571 [60.4%] males, median age 65 years [interquartile range 57-73 years] for the entire population); dyslipidemia (64.2%), hypertension (63.3%), diabetes (35.0%), and active smoking history (31.8%) were the most prevalent risk factors.After a median follow-up of 38 months (IQR 12-75 months), 59.3% patients had a bad outcome at discharge. A result of 26.1% had stroke recurrence (median time until recurrence: 9 months [IQR 12-84 months], with 12.9% cases presenting ≥2 recurrences), and 24.1% were dead (median time to death: 18.5 months [IQR 11-74 months]) at the final follow-up period. After multivariate adjustment, hypertension (HR 4.2, CI 95% 2.8-6.1; p<0.001) was the strongest predictor of recurrence. Additionally, diabetes (HR 2.6, CI 95% 2.0-3.5; p<0.001), bad functional outcome after recurrence (HR 2.3, CI 95% 1.9-2.9; p<0.001), age ≥65 years (HR 2.2, CI 95% 1.7-2.9; p<0.001), and active smoking (HR 1.8, CI 95% 1.3-2.3; p<0.001) were the strongest predictors of mortality. Conclusions: Atherosclerotic ischemic stroke has a high rate of recurrence, associated mainly with hypertension. Mortality is predicted by diabetes, bad functional outcome at recurrence, and older age.


Parasitology ◽  
2020 ◽  
pp. 1-6
Author(s):  
Bernard C. Meyer

Abstract This paper describes chronic features of neuroangiostrongyliasis (NAS), a long-term outcome of the disease that has not been adequately described. Current and past literature is predominantly limited to acute manifestations of NAS, and mention of chronic, ongoing clinical symptoms is usually limited to brief notes in a discussion of severe cases. This study investigated the long-term outcomes in ten individuals who were diagnosed with acute neuroangiostrongyliasis in Hawaii between 2009 and 2017. The study demonstrates a significant number of persons in Hawaii sustain residual symptoms for many years, including troublesome sensory paresthesia (abnormal spontaneous sensations of skin experienced as ‘burning, pricking, pins and needles’; also described as allodynia or hyperesthesia) and extremity muscle pains. As a consequence, employment and economic hardships, domestic relocations, and psychological impairments affecting personal relationships occurred. The study summarizes common features of chronic disease, sensory paresthesia and hyperesthesia, diffuse muscular pain, insomnia, and accompanying emotional distress; highlights the frequently unsuccessful endeavours of individuals struggling to find effective treatment; proposes pathogenic mechanisms responsible for prolonged illness including possible reasons for differences in disease presentation in Hawaii compared to Southeast Asia.


2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.


Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011237
Author(s):  
Silvia Masnada ◽  
Anna Pichiecchio ◽  
Manuela Formica ◽  
Filippo Arrigoni ◽  
Paola Borrelli ◽  
...  

ObjectiveAiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed.MethodsOnly patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed.ResultsPatients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported).ConclusionThe AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome.Classification of evidenceThis study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.


2013 ◽  
Vol 74 (1) ◽  
pp. 183-190
Author(s):  
Senair Alberto Ambros ◽  
Paulo Belmonte Abreu ◽  
Eloísa Elena Ferreira ◽  
Pdro Eugenio Ferreira ◽  
Luciana Estacia Ambros

Objective: To assess the metabolic alterations of the thalamus in subjects with schizophrenia compared to healthysubjects and to investigate whether specific schizophrenic symptoms are associated with metabolic alterationsmeasured by 1H MRS. Methods: This is a case-control study including patients with schizophrenia diagnosed usingthe Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, DMS-IV and the Operational CriteriaChecklist for Psychotic Illness (OPCRIT). Proton magnetic resonance spectroscopy (1H MRS) was used to assessmetabolite concentrations (N-acetylaspartate, choline, creatinine, myoionositol and lactacte) in the left and rightthalamus of 13 patients with schizophrenia and 13 healthy controls. Results: In this study, concentrations ofspecific metabolites in the thalamus, determined by 1H MRS, were similar for individuals with schizophrenia andcontrols. It was observed that cases with family history of schizophrenia and disorganized speech demonstrated areduction in the ratio of the metabolites NAA /Cho in the thalamic nuclei on the right side. However, those withorganized delusions, hallucinations and non-affective auditory hallucinations had an increase of metabolites on theright side compared to the left thalamus. Decreased thalamic metabolic activity in patients with positive symptomswas observed in contrast with those who had well-organized delusions and auditory non-affective hallucinations,core symptoms of schizophrenia. Conclusion: A lateralized thalamic involvement was verified, suggesting thatorganic and genetic factors compromise the right thalamus and that the disorganization associated with delusionsand hallucinations compromises the left thalamic nuclei. Further studies to investigate the correlation betweensymptoms and thalamic dysfunction are warranted. (Rev Neuropsiquiatr 2011;74:183-190)


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