BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review.
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ABSTRACT:
SUBMITTER: Nieto RR
PROVIDER: S-EPMC8242210 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Post-mortem brain investigations of schizophrenia have generated swathes of data in the last few decades implicating candidate genes and protein. However, the relation of these findings to peripheral biomarker indicators and symptomatology remain to be elucidated. While biomarkers for disease do not have to be involved with underlying pathophysiology and may be largely indicative of diagnosis or prognosis, the ideal may be a biomarker that is involved in underlying disease processes and which is therefore more likely to change with progression of the illness as well as potentially being more responsive to treatment. One of the main difficulties in conducting biomarker investigations for major psychiatric disorders is the relative inconsistency in clinical diagnoses between disorders such as bipolar and schizophrenia. This has led some researchers to investigate biomarkers associated with core symptoms of these disorders, such as psychosis. The aim of this review is to evaluate the contribution of post-mortem brain investigations to elucidating the pathophysiology pathways involved in schizophrenia and psychosis, with an emphasis on major neurotransmitter systems that have been implicated. This data will then be compared to functional neuroimaging findings as well as findings from blood based gene expression investigations in schizophrenia in order to highlight the relative overlap in pathological processes between these different modalities used to elucidate pathogenesis of schizophrenia. In addition we will cover some recent and exciting findings demonstrating microRNA (miRNA) dysregulation in both the blood and the brain in patients with schizophrenia. These changes are pertinent to the topic due to their known role in post-transcriptional modification of gene expression with the potential to contribute or underlie gene expression changes observed in schizophrenia. Finally, we will discuss how post-mortem studies may aid future biomarker investigations.
| S-EPMC3693064 | biostudies-literature
Project description:Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide single nucleotide polymorphism (SNP) data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT, and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was significantly associated with lower BACS scores (r?=?-0.17, p?=?6.6?×?10-4 at PT?=?1?×?10-4), but not with WRAT or EY. Among individuals with psychosis, PRSSCZ did not associate with variations in any of these three phenotypes. We further investigated the association between PRSSCZ and WRAT in more than 4500 healthy subjects from the Philadelphia Neurodevelopmental Cohort. The association was again null (p?>?0.3, N?=?4511), suggesting that different cognitive phenotypes vary in their etiologic relationship with schizophrenia.
| S-EPMC5895806 | biostudies-other
Project description:We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets.
2020-05-11 | GSE138082 | GEO
Project description:ObjectiveIdentification of biomarkers for cognitive dysfunction in schizophrenia is a priority for psychiatry research. Functional imaging studies suggest that intrinsic "resting state" hippocampal hyperactivity is a characteristic feature of schizophrenia. The relationships between this phenotype and symptoms of the illness, however, are largely unexplored. The authors examined resting hippocampal activity in schizophrenia patients and healthy comparison subjects and analyzed the relationship between intrinsic hippocampal activity and cognitive function in patients as measured by the MATRICS Consensus Cognitive Battery (MCCB).MethodTwenty-eight schizophrenia patients and 28 age-matched healthy comparison subjects underwent functional "resting state" 3-T MR scanning. Hippocampal activity was extracted by group independent component analysis. Correlation analyses were used to examine the relationship between hippocampal activity and MCCB composite and domain scores in patients, as well as between hippocampal activity and positive and negative symptoms.ResultsGreater activity of the right hippocampus at rest was observed in patients relative to comparison subjects. In patients, a significant negative correlation was observed between right hippocampal activity and composite MCCB T-score. The correlation was driven by the MCCB domains of attention/vigilance, working memory, and visual learning. Hippocampal activity was positively correlated with negative symptoms. MCCB scores were inversely correlated with negative symptoms.ConclusionsThese findings suggest that greater intrinsic hippocampal activity is a characteristic feature of schizophrenia that is broadly associated with cognitive dysfunction, and they support hippocampal activity as a candidate biomarker for therapeutic development.
| S-EPMC4085164 | biostudies-literature
Project description:Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses.
| S-EPMC9775399 | biostudies-literature
Project description:Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of "omics sciences", and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach.
| S-EPMC10049725 | biostudies-literature
Project description:Cognitive impairment is a core feature of schizophrenia which precedes the onset of full psychotic symptoms, even in the ultra-high-risk stage (UHR). Polygenic risk scores (PRS) can be computed for many psychiatric disorders and phenotyping traits, including scores for resilience. We explored the correlations between several PRS and neurocognition in UHR individuals. We included 107 UHR individuals; 29.9% of them converted to psychosis (UHR-C) while 57.0% did not (UHR-NC) during the 1-year follow-up. Cognitive performances were assessed with the Wechsler Adult Intelligence Scale estimating the Intelligence Quotient (IQ), the Trail Making Test, the verbal fluency, the Stroop test, and the Wisconsin card sorting test. Linear regression models were used to test their association with the PRS for schizophrenia, bipolar disorder, major depression, ADHD, cross-disorders, cognitive performance, intelligence, education attainment, and resilience to schizophrenia. UHR-C had a lower IQ than UHR-NC. The PRS for schizophrenia negatively correlated with IQ, while the PRS for cognitive performance and for resilience positively correlated with IQ. PRS for schizophrenia showed a significant correlation with working memory and processing speed indices. PRS for schizophrenia showed a higher effect on IQ in UHR-NC, and UHR-NC with high PRS for schizophrenia had a similar IQ as UHR-C. Conversely, UHR-C with a high PRS for resilience performed as well as UHR-NC. Our findings suggest that cognitive deficits may predate the onset of psychosis. The genetic architecture of schizophrenia seems to impacts the cognition in UHR-NC. Cognition is also mediated by PRS for resilience.
| S-EPMC8502171 | biostudies-literature
Project description:Modafinil, a wake-promoting agent believed to operate via the hypocretin/orexin system, has a similar clinical profile to that of conventional, dopaminergic stimulants but different biochemical and pharmacological properties. There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder. Recent research has focused on enhancing cognition in patients with schizophrenia because of the association between cognitive performance and functional outcome. Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. The results further suggest that patient characteristics such as overall current cognitive functioning levels, genetic polymorphisms, and medication status may be important mediators for the effectiveness of modafinil, allowing for future treatment to be targeted to those most likely to benefit. Currently, further research is required to address the potential benefits and risks of chronic administration of modafinil to patients with schizophrenia.
| S-EPMC2779875 | biostudies-literature
Project description:IntroductionGitelman syndrome(GS) is a rare inherited tubular disorder which is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. Here, we report a case of schizophrenia-like psychosis concomitant with GS and related literatures are reviewed.Case descriptionAn 18-year-old male patient with 1-week history of auditory hallucinations, sense of insecurity, delusions of reference and feelings of being followed and controlled by others unknown, insomnia was admitted to Psychiatry department in December, 2013. Hypokalemia and hypomagnesemia were noted. He was diagnosed as schizophrenia-like psychosis. Treatment with paliperidone at the dose of 6 mg/day and magnesium and potassium supplementations was commenced. However, electrolyte disturbances failed to improve following psychosis remission. Therefore, other underlying diseases resulting in electrolyte disturbances were suspected. Along with hypokalemia and hypomagnesemia, additional investigation showing metabolic alkalosis, hypocalciuria, renal loss of potassium, were consistent with GS. Gene analysis revealed this patient carried out c. 2687 G > A homozygous mutation of exon 23 in the SLC12A3 gene which led to p.Arg896Gln. Eventually, GS was identified. Thus, additional spironolactone (40 mg/day) combined with increased doses of oral potassium chloride sustained-release tablets (3.0 g/day) and potassium magnesium aspartate (0.3 g/day) were administered. During next half a year, fatigue resolved, paliperidone gradually tapered and eventually discontinued while psychosis maintained complete remission. His serum potassium was near normal (3.2-3.5 mmol/L), hypomagnesemia significantly improved (0.57-0.67 mmol/L).Discussion and evaluationElectrolyte abnormalities secondary to GS might cause or contribute to development of neuropsychiatric symptoms. In turn, hypokalemia was common among acute psychiatric inpatients. As a consequence, when concomitant with psychosis, GS was readily concealed.ConclusionElectrolyte disturbances are common in acute psychiatric patients. However, when electrolyte disturbances are not improved following psychosis remission, other underlying diseases such as GS should be considered.
| S-EPMC4920738 | biostudies-literature
Project description:In schizophrenia, impairments in neurocognition (NC) and social cognition (SC) are associated with reduced functional capacity (FC) and poor real-world functioning (RWF). In this semi-systematic review, we examined this association across a range of research questions. We conducted a systematic search in Embase and MEDLINE from 2005 to 2019, and conducted additional pragmatic searches. After screening of titles, abstracts and full-texts, we included 564 citations, of which 44 (26 primary studies, 15 systematic reviews and 3 narrative reviews) were prioritized for reporting. Both NC and SC were significantly associated with functioning, with slightly stronger association for SC. Effect sizes were generally larger for FC than for RWF. NC showed stronger associations with occupational functioning and independent living, and SC with social functioning. Baseline cognition predicted long-term RWF up to 20 years of follow-up, though long-term data were limited for SC. Cognitive remediation improved RWF functioning, especially when it was combined with psychosocial rehabilitation. SC mediated the relationship of NC with functioning. Negative symptoms appeared to mediate and moderate the association of cognition with functioning. Other factors involved included severity of cognitive dysfunction, metacognition, depression and choice of RWF instrument. We discuss potential implications for studies of pharmacological cognitive interventions in schizophrenia - the relevance of both NC and SC, the advantage of adjunctive psychosocial rehabilitation, the role of relevant moderating and mediating variables, and the challenges with RWF instrument selection. Successful cognitive interventions could allow patients with schizophrenia to improve their potential for community functioning.
| S-EPMC8488595 | biostudies-literature