Hippocampal volume recovery with real-time functional MRI amygdala neurofeedback emotional training for posttraumatic stress disorder.

Background: Small hippocampal volume is a prevalent neurostructural abnormality in posttraumatic stress disorder (PTSD). However, whether the hippocampal atrophy is the cause of disease symptoms or a pre-existing risk factor and whether it is a reversible alteration or a permanent trait are unclear. The trait- or state-dependent alteration could also differ among the hippocampal subfields.

Brain activity mediators of PTSD symptom reduction during real-time fMRI amygdala neurofeedback emotional training.

Self-regulation of brain activation with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is emerging as a promising treatment for psychiatric disorders. The association between the regulation and symptom reduction, however, has not been consistent, and the mechanisms underlying the symptom reduction remain poorly understood. The present study investigated brain activity mediators of the amygdala rtfMRI-nf training effect on combat veterans' PTSD symptom reduction.

Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study.

Background: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population.

Real-time fMRI amygdala neurofeedback positive emotional training normalized resting-state functional connectivity in combat veterans with and without PTSD: a connectome-wide investigation.

Self-regulation of brain activation using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is an emerging approach for treating mood and anxiety disorders. The effect of neurofeedback training on resting-state functional connectivity warrants investigation as changes in spontaneous brain activation could reflect the association between sustained symptom relief and brain alteration. We investigated the effect of amygdala-focused rtfMRI-nf training on resting-state functional connectivity in combat veterans with and without posttraumatic stress disorder (PTSD) who were trained to increase a feedback signal reflecting left amygdala activity while recalling positive autobiographical memories (Zotev et al.

Tracking resting state connectivity dynamics in veterans with PTSD.

Posttraumatic stress disorder (PTSD) is a trauma- and stressor-related disorder that may emerge following a traumatic event. Neuroimaging studies have shown evidence of functional abnormality in many brain regions and systems affected by PTSD. Exaggerated threat detection associated with abnormalities in the salience network, as well as abnormalities in executive functions involved in emotions regulations, self-referencing and context evaluation processing are broadly reported in PTSD.

Real-time fMRI neurofeedback training of the amygdala activity with simultaneous EEG in veterans with combat-related PTSD.

Posttraumatic stress disorder (PTSD) is a chronic and disabling neuropsychiatric disorder characterized by insufficient top-down modulation of the amygdala activity by the prefrontal cortex. Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging method with potential for modifying the amygdala-prefrontal interactions. We report the first controlled emotion self-regulation study in veterans with combat-related PTSD utilizing rtfMRI-nf of the amygdala activity.

Connectome-wide investigation of altered resting-state functional connectivity in war veterans with and without posttraumatic stress disorder.

Altered resting-state functional connectivity in posttraumatic stress disorder (PTSD) suggests neuropathology of the disorder. While seed-based fMRI connectivity analysis is often used for the studies, such analysis requires defining a seed location , which restricts search scope and could bias findings toward presupposed areas. Recently, a comprehensive exploratory voxel-wise connectivity analysis, the connectome-wide association approach, has been introduced using multivariate distance matrix regression (MDMR) for resting-state functional connectivity analysis.

Treatment of bipolar depression with minocycline and/or aspirin: an adaptive, 2×2 double-blind, randomized, placebo-controlled, phase IIA clinical trial.

Given evidence of chronic inflammation in bipolar disorder (BD), we tested the efficacy of aspirin and minocycline as augmentation therapy for bipolar depression. Ninety-nine depressed outpatients with BD were enrolled in a 6 week, double-blind, placebo-controlled trial, and randomized to one of four groups: active minocycline (100 mg b.i.

Kynurenic acid is reduced in females and oral contraceptive users: Implications for depression.

The incidence of depression is approximately 2-fold greater in women than men but the biological mechanisms underlying this phenomenon remain unclear. One potential mechanism that has been understudied is immune function, which is modulated by sex hormones and differs considerably between males and females. The immune-regulating kynurenine pathway previously has been implicated in the pathogenesis of mood disorders.

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder.

Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites.

Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder.

Inflammation, which may be present in a subgroup of individuals with major depressive disorder (MDD), activates the kynurenine metabolic pathway to produce kynurenine metabolites kynurenic acid (KynA) and quinolinic acid (QA). We have previously reported an association between the ratio of KynA to QA and hippocampal volume in MDD. In animals, inflammation leads to deficits in incentive motivation.

Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.

Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD).

Neuroprotective kynurenine metabolite indices are abnormally reduced and positively associated with hippocampal and amygdalar volume in bipolar disorder.

Inflammation-related changes in the concentrations of kynurenine-pathway metabolites occur in depression secondary to medical conditions but have not been well characterized in primary bipolar disorder (BD), with contradictory results potentially attributable to the presence or absence of psychosis and/or medication effects. In contrast, reductions in hippocampal and amygdalar volume that theoretically reflect dendritic atrophy occurring in the context of a neurotoxic process are commonly reported in unmedicated BD patients. Here we tested whether the concentrations of putatively neuroprotective (kynurenic acid, KynA) and neurotoxic (3-hydroxy-kynurenine, 3HK and quinolinic acid, QA) kynurenine-pathway metabolites were altered in primary BD and whether these metabolites were associated with hippocampal and amygdalar volume.

Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder.

Inflammation-related changes in the concentrations of kynurenine pathway metabolites occur in depression secondary to medical conditions but are not firmly established in primary mood disorders. Reductions in hippocampal and amygdalar volume that putatively reflect dendritic atrophy are widely reported in major depressive disorder (MDD). Here we tested whether the relative serum concentrations of putatively neuroprotective (kynurenic acid (KA)) and neurotoxic (3-hydroxykynurenine (3HK) and quinolinic acid (QA)) kynurenine pathway metabolites were altered in primary MDD and whether these metabolites were associated with hippocampal and amygdalar volume.