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 …
Disruption of White Matter Integrity in Bipolar Depression as a Possible Structural Marker of Illness
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
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…
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…
Tract-specific white matter structural disruption in patients with bipolar disorder
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…
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…
Spectroscopic correlates of antidepressant response to sleep deprivation and light therapy: a 3.0 Tesla study of bipolar depression.
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…
Neural responses to emotional stimuli in comorbid borderline personality disorder and bipolar depression
"\"Borderline personality disorder (BPD) is a severe clinical condition characterised by different maladaptive traits such as impulsivity and affective lability. Mood and emotion dysregulation are core features of affective disorders. Indeed patients affected by mood disorder (MD) have a significantly higher prevalence of comorbid BPD, resulting in more unstable mood and poorer response to medication. Blood oxygen level-dependent functional magnetic resonance imaging has been used to investigate the neural correlates of emotional face processing. Images for each subject were entered into an analysis of variance (ANOVA) dividing participants into three groups (MD, MD + BPD, Controls). MD + B…