Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder

2013

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-beta (GSK3-beta). The less active GSK3-beta promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-beta gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-beta promoter rs334558 polymorphism on WM microstructure, using DTI and …

Disruption of White Matter Integrity in Bipolar Depression as a Possible Structural Marker of Illness

2011

Background: Diffusion tensor imaging allows the study of integrity of white matter (WM) tracts. Literature suggests that WM integrity could be altered in bipolar disorder. Heterogeneity of brain imaging methods, the studied samples, and drug treatments make localization, nature, and severity of the WM abnormalities unclear. Methods: We applied tract-based spatial statistics of diffusion tensor imaging measures to compare fractional anisotropy (FA), mean, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by a major depressive episode without psychotic features with a diagnosis of bipolar disorder type I and 21 unrelated healthy volunteers f…

Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

2011

Background: Mood disorders are associated with the highest increase of attempted and completed suicide. Suicidality in major depressive disorder and in schizophrenia has been associated with reduced gray matter volumes in orbitofrontal cortex. Lithium reduces the suicide risk of patients with bipolar disorder (BD) to the same levels of the general population, and can increase GM volumes. We studied the effect of a positive history of attempted suicide and ongoing lithium treatment on regional GM volumes of patients affected by bipolar depression. Methods: With a correlational design, we studied 57 currently depressed inpatients with bipolar disorder: 19 with and 38 without a positive histor…

Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and Medication Load Influence White Matter Structure in Schizophrenia

2014

<b><i>Background:</i></b> Diffusion tensor imaging (DTI) studies have shown a widespread disruption of white matter (WM) microstructure in schizophrenia. Furthermore, higher fractional anisotropy (FA) has been consistently correlated with the severity of psychotic symptoms. Antipsychotic drugs (APDs) affect lipid homeostasis. Gene polymorphisms in sterol regulatory element binding transcription factor (SREBF)-1 and SREBF-2 have been associated with schizophrenia. <b><i>Methods:</i></b> In a sample of 65 patients affected by chronic schizophrenia, we investigated the effect of ongoing APD medication, SREBF-1 rs11868035<b> </b>polymo…

Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients

2007

Gene polymorphisms in the mammalian biological clock system influence individual rhythms. A single nucleotide polymorphism (SNP) in the 3' flanking region of CLOCK (3111 T/C; rs1801260) influenced diurnal preference in healthy humans and caused sleep phase delay and insomnia in patients affected by bipolar disorder. Genes of the biological clock are expressed in many brain structures other than in the 'master clock' suprachiasmatic nuclei. These areas, such as cingulate cortex, are involved in the control of many human behaviors. Clock genes could then bias 'nonclock' functions such as information processing and decision making. Thirty inpatients affected by a major depressive episode under…

Tract-specific white matter structural disruption in patients with bipolar disorder

2011

Benedetti F, Absinta M, Rocca MA, Radaelli D, Poletti S, Bernasconi A, Dallaspezia S, Pagani E, Falini A, Copetti M, Colombo C, Comi G, Smeraldi E, Filippi M. Tract-specific white matter structural disruption in patients with bipolar disorder. Bipolar Disord 2011: 13: 414–424. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives:  A growing body of evidence suggests that, independent of localized brain lesions, mood disorders can be associated with dysfunction of brain networks involved in the modulation of emotional and cognitive behavior. We used diffusion tensor (DT) tractography to quantify the presence and extent of structural injury to the connections betwe…

P1-238: ITALIAN CONSENSUS RECOMMENDATIONS FOR THE ETIOLOGICAL DIAGNOSIS IN MEMORY CLINICS

2019

MYD88 L265P mutation and interleukin‐10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central …

2021

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reac…

Emotional reactivity in chronic schizophrenia: structural and functional brain correlates and the influence of adverse childhood experiences

2011

Background. Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression). Method. Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural response…

Neural and genetic correlates of antidepressant response to sleep deprivation - A functional magnetic resonance imaging study of moral valence decisi…

2007

Context: Total sleep deprivation combined with light therapy causes rapid amelioration of bipolar depression. A polymorphism in the promoter for the serotonin transporter influences both antidepressant response and the structure and function of specific brain areas. Objective: To determine whether antidepressant therapy or the genotype of the serotonin transporter influence the pattern of neural response to a task targeting the depressive biases in information processing (moral valence decision). Design: Before-and-after trial studying the biologic correlates of response to treatment. Setting: University hospital. Patients: Twenty inpatients with bipolar depression. Intervention: Repeated t…

Spectroscopic correlates of antidepressant response to sleep deprivation and light therapy: a 3.0 Tesla study of bipolar depression.

2007

Glutamate is the primary excitatory neurotransmitter of the human brain, and recent findings suggest a role for the glutamatergic system in the pathophysiology and treatment of mood disorders. Single proton magnetic resonance spectroscopy (1H-MRS) was used to study the relative in vivo levels of brain neural metabolites. We evaluated the effect of antidepressant treatments on the relative concentration of unresolved glutamate and glutamine (Glx) with GABA contamination (2.35 ppm peak) using single voxel 1H-MRS at 3.0 Tesla. We studied 19 inpatients (7 males, 12 females) affected by bipolar disorder type 1, current depressive episode without psychotic features, before and after 1 week of tre…

Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-beta activity

2010

At the crossroad of multiple pathways regulating trophism and metabolism, glycogen synthase kinase (GSK)3 is considered a key factor in influencing the susceptibility of neurons to harmful stimuli (neuronal resilience) and is a target for several psychiatric drugs that directly inhibit it or increase its inhibitory phosphorylation. Inhibition of GSK3 prevents apoptosis and could protect against the neuropathological processes associated with psychiatric disorders. A GSK3-beta promoter single-nucleotide polymorphism (rs334558) influences transcriptional strength, and the less active form was associated with less detrimental clinical features of mood disorders. Here we studied the effect of r…

Italian consensus recommendations for a biomarker‐based aetiological diagnosis in mild cognitive impairment patients

2019

Background and purpose: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. Methods: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology – Società Italiana di Neurologia per le Demenze; neuroradiology – Associazione Italiana di Neuroradiologia; b…