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…
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…
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…
Correlati neurali del processo schizofrenico.
Self-awareness of cognitive functioning in schizophrenia: Patients and their relatives
"Cognitive impairment has been recognized since the earliest descriptions of schizophrenia as a core feature of the illness and different programmes have been developed to remediate these deficits. In all likelihood it is important for compliance and adherence to treatment that not only the patients but also their relatives be aware of the patients; cognitive deficits. Sixty-two patients with a diagnosis of schizophrenia and, for each one of them, one family member and an informant from the medical staff, were recruited and administered the Schizophrenia Cognition Rating Scale (SCoRS) ratings. Patients were tested for cognitive deficits with a neuropsychological battery and their performanc…
Emotional reactivity in chronic schizophrenia: structural and functional brain correlates and the influence of adverse childhood experiences
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…
What we learn about bipolar disorder from large-scale neuroimaging
Abstract MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Workin…
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…
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…
Computer-aided neurocognitive remediation in schizophrenia: durability of rehabilitation outcomes in a follow-up study.
Cognitive deficits in patients with schizophrenia constitute a limiting factor to the chances of rehabilitation of daily living abilities, like personal and relational autonomy and working ability. Cognitive Remediation Therapy (CRT) is a rehabilitative technique that aims at the recovery of single cognitive functions through the execution of massive exercises of impaired cognitive domains. This study aims to establish if the results achieved through an intensive deficit-specific neurocognitive treatment of three months duration, were maintained over time. The sample consists in 100 patients diagnosed with schizophrenia according to the criteria of DSM IV. Patients were assessed on cognitiv…