Neuroimaging correlates of emotional response-inhibition discriminate between young depressed adults with and without sub-threshold bipolar symptoms (Emotional Response-inhibition in Young Depressed Adults).

Background: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-).

Method: This study included 118 medication-free young adults (15 - 30 yrs.

Integrative analysis of lithium treatment associated effects on brain structure and peripheral gene expression reveals novel molecular insights into mechanism of action.

Lithium is a highly effective medication for bipolar disorder, but its mechanism of action remains unknown. In this study, brain MRI scans and blood samples for gene expression (total of 110 scans and 109 blood samples) were collected from 21 bipolar subjects before and after 2 and 8 weeks of lithium monotherapy and at the same time-points from untreated 16 healthy controls. We used linear mixed-effects models to identify brain structural features and genes with expression changed after lithium treatment, with correction for multiple testing, and correlated their concurrent changes to identify molecular pathways associated with lithium effects.

Intrinsic functional connectivity during continuous maintenance and suppression of emotion in bipolar disorder.

Resting-state connectivity studies, which examine unconstrained low frequency BOLD fluctuations, have reported inconsistent abnormalities in bipolar disorder (BP). In this study, we investigated intrinsic brain connectivity under the constraints of a Continuous Emotion Regulation Task (CERT) in BP patients in depressed (BPD) and manic (BPM) states, along with healthy control participants. Medication-free participants, with either a diagnosis of BP (BPD = 27, BPM = 30) or healthy controls (N = 33) were included.

Administration of Sub-anesthetic Dose of Ketamine and Electroconvulsive Treatment on Alternate Week Days in Patients with Treatment Resistant Depression: A Double Blind Placebo Controlled Trial.

Introduction And Background: Patients with depression who fail to respond to at least two antidepressants in their current episode are considered to have Treatment Resistant Depression (TRD). ECT is an effective treatment of TRD but cognitive side effects limit its use. Ketamine elicits a rapid antidepressant response in sub-anesthetic repeated doses.

Resting State Functional Connectivity of Dorsal Raphe Nucleus and Ventral Tegmental Area in Medication-Free Young Adults With Major Depression.

This study has, for the first time, investigated the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) resting state whole-brain functional connectivity in medication-free young adults with major depression (MDD), at baseline and in relationship to treatment response. A total of 119 subjects: 78 MDD (24 ± 4 years.) and 41 Healthy Controls (HC) (24 ± 3 years) were included in the analysis.

Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response.

Background: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC).

Methods: One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test.

Lithium monotherapy associated longitudinal effects on resting state brain networks in clinical treatment of bipolar disorder.

Objectives: Lithium is one of the most effective and specific treatments for bipolar disorder (BP), but the neural mechanisms by which lithium impacts symptoms remain unclear. Past research has been limited by a reliance on cross-sectional designs, which does not allow for identification of within-person changes due to lithium and has not examined communication between brain regions (ie, networks). In the present study, we prospectively investigated the lithium monotherapy associated effects in vivo on the brain connectome in medication-free BP patients.

Spectral Dynamics of Resting State fMRI Within the Ventral Tegmental Area and Dorsal Raphe Nuclei in Medication-Free Major Depressive Disorder in Young Adults.

Dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) are major brainstem monamine nuclei consisting of serotonin and dopamine neurons respectively. Animal studies show that firing patterns in both nuclei are altered when animals exhibit depression like behaviors. Functional MRI studies in humans have shown reduced VTA activation and DRN connectivity in depression.

Lithium monotherapy associated clinical improvement effects on amygdala-ventromedial prefrontal cortex resting state connectivity in bipolar disorder.

Background: This study, for the first time, investigated lithium monotherapy associated effects on amygdala- ventromedial prefrontal cortex (vMPFC) resting-state functional connectivity and correlation with clinical improvement in bipolar disorder (BP) METHODS: Thirty-six medication-free subjects - 24 BP (12 hypomanic BPM) and 12 depressed (BPD)) and 12 closely matched healthy controls (HC), were included. BP subjects were treated with lithium and scanned at baseline, after 2 weeks and 8 weeks. HC were scanned at same time points but were not treated.

Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in Peripheral Lymphocytes.

Background: This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD).

Method: Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment.

Quetiapine Extended Release Open-Label Treatment Associated Changes in Amygdala Activation and Connectivity in Anxious Depression: An fMRI Study.

Background: This study investigated extended release quetiapine (quetiapine XR) associated changes in functional MRI (fMRI) measures of task-induced amygdalar activation and resting state connectivity in anxious unipolar major depressive disorder (AMDD).

Methods: Anxious unipolar major depressive disorder patients (n = 15) (17-item Hamilton Depression Rating Scale (HAM-D) >18 and Hamilton Anxiety Scale (HAM-A) >18) and closely matched healthy control (HC) subjects were compared at baseline for task induced amygdala activation and resting state connectivity on fMRI. Subsequently, AMDD patients were treated for 8 weeks with open-label quetiapine XR.

Resting State Brain Network Disturbances Related to Hypomania and Depression in Medication-Free Bipolar Disorder.

Research on resting functional brain networks in bipolar disorder (BP) has been unable to differentiate between disturbances related to mania or depression, which is necessary to understand the mechanisms leading to each state. Past research has also been unable to elucidate the impact of BP-related network disturbances on the organizational properties of the brain (eg, communication efficiency). Thus, the present work sought to isolate network disturbances related to BP, fractionate these into components associated with manic and depressive symptoms, and characterize the impact of disturbances on network function.

The effects of DAT1 genotype on fMRI activation in an emotional go/no-go task.

Dopaminergic brain circuits participate in emotional processing and impulsivity. The dopamine transporter (DAT) modulates dopamine reuptake. A variable number tandem repeat (VNTR) in the dopamine transporter gene (DAT1) affects DAT expression.

Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania.

Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects.

Neurochemical abnormalities in unmedicated bipolar depression and mania: a 2D 1H MRS investigation.

The neurobiology and neurochemistry of bipolar disorder and its different phases are poorly understood. This study investigated metabolite abnormalities in both unmedicated bipolar depression as well as mania using 2D 1H magnetic resonance spectroscopy imaging (MRSI). MRSI data were obtained from 24 unmedicated bipolar disorder (BP) subjects (12 (hypo)manic (BPM)) and 12 depressed (BPD), and 20 closely matched healthy controls.

Emotional response inhibition in bipolar disorder: a functional magnetic resonance imaging study of trait- and state-related abnormalities.

Background: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects.

Methods: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks.

Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial.

Background: Recent studies indicate that modulation of glutamate neurotransmission is associated with antidepressant response. Lamotrigine, an anticonvulsant which decreases presynaptic glutamate release, has been shown to be effective in the depressive phase of bipolar disorder (BD-D); however, only 40-50% of patients have a full response. This pilot study investigated whether memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist approved for Alzheimer's disease, can augment the effects of lamotrigine.

Neural activation during facial emotion processing in unmedicated bipolar depression, euthymia, and mania.

Background: Studies incorporating direct comparisons across all phases of bipolar (BP) disorder are needed to elucidate the pathophysiology of bipolar disorder. However, functional neuroimaging studies that differentiate bipolar mood states from each other and from healthy subjects are few and have yielded inconsistent findings.

Methods: One hundred five unmedicated adults were recruited: 30 with current bipolar depression (BPD), 30 with current bipolar hypomania or mania (BPM), 15 bipolar euthymic (BPE), and 30 healthy control subjects (HC).

Striatal dopamine transporter availability in unmedicated bipolar disorder.

Objectives: Dopamine transmission abnormalities have been implicated in the etiology of bipolar disorder (BPD). However, there is a paucity of receptor imaging studies in BPD, and little information is available about the dopamine system in BPD. Reuptake of synaptic dopamine by the dopamine transporter (DAT) is the principal mechanism regulating dopamine neurotransmission, and is often used as a marker for presynaptic dopamine function.