Transdiagnostic role of glutamate and white matter damage in neuropsychiatric disorders: A Systematic Review

Luttenbacher, Ines; Philips, Angela; Kazemi, Reza; Hadipour, Abed L.; I, Sanghvi; Martinez, Julian; Adamson, Maheen

doi:10.1016/j.jpsychires.2021.12.042

Cited by 8 publications

(8 citation statements)

References 408 publications

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“…Accordingly, NMDARs involvement would be more evident for schizophrenia and severe BD forms resistant to pharmacological treatment and responsive to ECT. Our hypothesis about NMDARs is in agreement with other research groups also prompting a transdiagnostic continuum in white matter abnormalities and glutamatergic alterations from anxiety disorders to mood disorder and schizophrenia 94–96 …”

Section: Discussionsupporting

confidence: 90%

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The role of NMDA receptors in bipolar disorder: A systematic review

et al. 2023

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ObjectivesGlutamatergic transmission and N‐methyl‐D‐aspartate receptors (NMDARs) have been implicated in the pathophysiology schizophrenic spectrum and major depressive disorders. Less is known about the role of NMDARs in bipolar disorder (BD). The present systematic review aimed to investigate the role of NMDARs in BD, along with its possible neurobiological and clinical implications.MethodsWe performed a computerized literature research on PubMed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement, using the following string: ((“Bipolar Disorder”[Mesh]) OR (manic‐depressive disorder[Mesh]) OR (“BD”) OR (“MDD”)) AND ((NMDA [Mesh]) OR (N‐methyl‐D‐aspartate) OR (NMDAR[Mesh]) OR (N‐methyl‐D‐aspartate receptor)).ResultsGenetic studies yield conflicting results, and the most studied candidate for an association with BD is the GRIN2B gene. Postmortem expression studies (in situ hybridization and autoradiographic and immunological studies) are also contradictory but suggest a reduced activity of NMDARs in the prefrontal, superior temporal cortex, anterior cingulate cortex, and hippocampus.ConclusionsGlutamatergic transmission and NMDARs do not appear to be primarily involved in the pathophysiology of BD, but they might be linked to the severity and chronicity of the disorder. Disease progression could be associated with a long phase of enhanced glutamatergic transmission, with ensuing excitotoxicity and neuronal damage, resulting into a reduced density of functional NMDARs.

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Section: Discussionsupporting

confidence: 90%

“…hypothesis about NMDARs is in agreement with other research groups also prompting a transdiagnostic continuum in white matter abnormalities and glutamatergic alterations from anxiety disorders to mood disorder and schizophrenia. [94][95][96]…”

Section: Nmdar-mediated Transmission In Bd: a Transnosographic Perspe...mentioning

confidence: 99%

The role of NMDA receptors in bipolar disorder: A systematic review

et al. 2023

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“…However, the longitudinal fasciculi were also frequently affected with lower fractional anisotropy (right > left) as were regions in the cingulum, left > right ( Zhao et al, 2022 ). As far as specificity, four of the neuropsychiatric disorders studied, obsessive-compulsive disorder, major depressive disorder, bipolar disorder, and schizophrenia had abnormal DTI measures in the corpus callosum and the superior longitudinal fasciculus, to varying degrees (schizophrenia the worst) ( Luttenbacher et al, 2022 ). As far as the impact on the patients, decreased fractional anisotropy has been linked to the deficits in patients with schizophrenia in both positive and negative symptoms, as well as executive, memory, and social dysfunction ( Karlsgodt, 2020 ).…”

Section: Imagingmentioning

confidence: 99%

Neuroimaging in schizophrenia: A review article

et al. 2022

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In this review article we have consolidated the imaging literature of patients with schizophrenia across the full spectrum of modalities in radiology including computed tomography (CT), morphologic magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and magnetoencephalography (MEG). We look at the impact of various subtypes of schizophrenia on imaging findings and the changes that occur with medical and transcranial magnetic stimulation (TMS) therapy. Our goal was a comprehensive multimodality summary of the findings of state-of-the-art imaging in untreated and treated patients with schizophrenia. Clinical imaging in schizophrenia is used to exclude structural lesions which may produce symptoms that may mimic those of patients with schizophrenia. Nonetheless one finds global volume loss in the brains of patients with schizophrenia with associated increased cerebrospinal fluid (CSF) volume and decreased gray matter volume. These features may be influenced by the duration of disease and or medication use. For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. However, these findings may vary depending upon the negative or positive symptomatology manifested in the patients. MR spectroscopy generally shows low N-acetylaspartate from neuronal loss and low glutamine (a neuroexcitatory marker) but glutathione may be elevated, particularly in non-treatment responders. The literature in schizophrenia is difficult to evaluate because age, gender, symptomatology, comorbidities, therapy use, disease duration, substance abuse, and coexisting other psychiatric disorders have not been adequately controlled for, even in large studies and meta-analyses.

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“…In a functional magnetic resonance imaging study of patients with MDD, BD, and SZ, transdiagnostic dysconnectivities were identified within somatomotor and salience networks and between subcortical-limbic and subcortical-dorsal attention networks 27 . Another systematic review of 401 neuroimaging studies found that the concentrations of glutamate-glutamine and white matter abnormalities were commonly found in patients with MDD, BD, and SZ 28 …”

Section: Discussionmentioning

confidence: 99%

“…27 Another systematic review of 401 neuroimaging studies found that the concentrations of glutamateglutamine and white matter abnormalities were commonly found in patients with MDD, BD, and SZ. 28 We performed a subgroup analysis where the sample was segmented by response to antidepressant treatment and found that parents of adolescents with a poor response to antidepressant treatment were more likely to be diagnosed with MDD and BD than parents of adolescents with a good response to antidepressant treatment. In addition, parents of the individuals who were resistant to both SSRIs and non-SSRIs were more likely to be diagnosed with MDD than parents of the individuals who were only resistant to SSRIs.…”

Section: Discussionmentioning

confidence: 99%

Risk of parental psychiatric disorders among adolescents with major depressive disorder according to response to antidepressant treatment: does the type of antidepressant matter?

et al. 2023

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Background The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders. Methods In all, 1,758 adolescents aged 12–19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed. Results The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder. Discussion Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent’s sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.

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Transdiagnostic role of glutamate and white matter damage in neuropsychiatric disorders: A Systematic Review

Cited by 8 publications

References 408 publications

The role of NMDA receptors in bipolar disorder: A systematic review

The role of NMDA receptors in bipolar disorder: A systematic review

Neuroimaging in schizophrenia: A review article

Risk of parental psychiatric disorders among adolescents with major depressive disorder according to response to antidepressant treatment: does the type of antidepressant matter?

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