Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder
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 …
Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and Medication Load Influence White Matter Structure in Schizophrenia
<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
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…
Neural and genetic correlates of antidepressant response to sleep deprivation - A functional magnetic resonance imaging study of moral valence decision, in bipolar depression
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…
Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-beta activity
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…