BDNF rs6265 differentially influences neurometabolites in the anterior cingulate of healthy and bipolar disorder subjects.

Brain-derived neurotrophic factor (BDNF) is the most abundant brain neurotrophin and plays a critical role in neuronal growth, survival and plasticity, implicated in the pathophysiology of Bipolar Disorders (BD). The single-nucleotide polymorphism in the BDNF gene (BDNF rs6265) has been associated with decreased hippocampal BDNF secretion and volume in met carriers in different populations, although the val allele has been reported to be more frequent in BD patients. The anterior cingulate cortex (ACC) is a key center integrating cognitive and affective neuronal connections, where consistent alterations in brain metabolites such as Glx (Glutamate + Glutamine) and N-acetylaspartate (NAA) have been consistently reported in BD.

Association between CACNA1C gene rs100737 polymorphism and glutamatergic neurometabolites in bipolar disorder.

Abnormalities in Ca homeostasis in Bipolar Disorders (BD) have been associated with impairments in glutamatergic receptors and voltage-gated calcium channels. Increased anterior cingulate cortex (ACC) glutamatergic neurometabolites have been consistently disclosed in BD by proton magnetic resonance spectroscopy (H-MRS). A single nucleotide polymorphism (SNP) in the CACNA1C gene (rs1006737), which encodes the alpha 1-C subunit of the L-type calcium channel, has been associated with BD and is reported to modulate intra-cellular Ca.

Effects of antidepressant drug therapy with or without physical exercise on inflammatory biomarkers in major depressive disorder: a systematic review and meta-analysis of randomized controlled trials.

Objective: To conduct a systematic review and meta-analysis of the effects of antidepressant drug therapy (with or without physical exercise) on peripheral inflammatory markers in patients with major depressive disorder (MDD).

Methods: MEDLINE, PyscINFO, Embase, and Google Scholar databases were searched until May 2020. Randomized trials that measured at least one inflammatory biomarker and included adult outpatients with MDD under antidepressant drug therapy (any drug) with or without physical exercise (any modality) were eligible.

Anterior cingulate cortex neurometabolites in bipolar disorder are influenced by mood state and medication: A meta-analysis of H-MRS studies.

The anterior cingulate cortex (ACC), a brain region that mediates affect and cognition by connecting the frontal cortex to limbic structures, has been consistently implicated in the neurobiology of Bipolar Disorder (BD). Proton magnetic resonance spectroscopy (H-MRS) studies have extensively compared in vivo neurometabolite levels of BD patients and healthy controls (HC) in the ACC. However, these studies have not been analyzed in a systematic review or meta-analysis and nor has the influence of mood state and medication on neurometabolites been examined in this cortical region.

Altered brain creatine cycle metabolites in bipolar I disorder with childhood abuse: A H magnetic resonance spectroscopy study.

Background: Childhood abuse (CA) is a risk factor for a number of psychiatric disorders and has been associated with higher risk of developing bipolar disorders (BD). CA in BD has been associated with more severe clinical outcomes, but the neurobiological explanation for this is unknown. Few studies have explored in vivo measurement of brain metabolites using proton magnetic resonance spectroscopy (H-MRS) in CA and no studies have investigated the association of CA severity with brain neurometabolites in BD.

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide.

ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization.

Bipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (H-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio.

A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study.

Background: Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial.

Objective: The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals.

Lithium-associated anterior cingulate neurometabolic profile in euthymic Bipolar I disorder: A H-MRS study.

Objective: In the treatment of Bipolar disorder (BD), achieving euthymia is highly complex and usually requires a combination of mood stabilizers. The mechanism of action in stabilizing mood has not been fully elucidated, but alterations in N-Acetylaspartate (NAA), Myo-Inositol (mI) and Choline (Cho) have been implicated. Proton magnetic resonance spectroscopy (H-MRS) is the gold standard technique for measuring brain NAA, Cho and mI in vivo.

Anterior Cingulate Cortex Glutamatergic Metabolites and Mood Stabilizers in Euthymic Bipolar I Disorder Patients: A Proton Magnetic Resonance Spectroscopy Study.

Background: Bipolar disorder is a chronic and recurrent illness characterized by depressive and manic episodes. Proton magnetic resonance spectroscopy (H-MRS) studies have demonstrated glutamate (Glu) system abnormalities in BD, but it is unclear how Glu varies among mood states and how medications modulate it. The objective of this study was to investigate the influence of mood stabilizers on anterior cingulate cortex Glu levels using H-MRS during euthymia.

Investigation of associations between recurrence of major depressive disorder and spinal posture alignment: A quantitative cross-sectional study.

The aim of this study was to investigate associations between poor spinal posture and the recurrence of major depressive episodes and severity of symptoms in patients with major depressive disorder (MDD). This was a cross-sectional quantitative study of MDD patients. Outpatients were recruited from consecutive admissions at a mood disorders unit of a tertiary psychiatric hospital.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls.

Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in euthymic bipolar I disorder.

Bipolar disorder (BD) has been consistently associated with abnormalities in the Glutamate/GABA-Glutamine cycle. Magnetic resonance spectroscopy (MRS) studies have reported increased brain Glutamate (Glu) and Glx (Glu+Glutamine) in subjects with BD. However, data on separate measures of GABA and Glutamine (Gln) in BD are sparse due to overlapping resonant signals.

Leukocyte telomerase activity and antidepressant efficacy in bipolar disorder.

Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA from damage. Recently, shorten telomeres length has been reported in bipolar disorder (BD) and depression. The enzyme telomerase regulates telomeres׳ length, which has been associated with cellular viability; however it is not clear how telomerase may be involved in the pathophysiology and therapeutics of BD.

Lithium decreases plasma adiponectin levels in bipolar depression.

Lithium, a first line treatment for bipolar disorder (BD), has been associated with significant weight gain, but the mechanisms underlying this phenomenon are still unclear. It has been suggested that changes in production/release of adipokines - molecules secreted by adipose tissue presenting anti-inflammatory (adiponectin) and pro-inflammatory (leptin, resistin) properties - might be implicated. Adiponectin, resistin and leptin were assessed in 25 acutely depressed BD individuals (88% medication-free and 68% treatment-naive) at baseline and after 6 weeks of lithium therapy, and in 23 healthy controls matched by age.

Facial emotion recognition and its correlation with executive functions in bipolar I patients and healthy controls.

Introduction: The ability to recognize facial emotions is altered in patients with Bipolar Disorder (BD) during mood episodes and even in euthymia, while cognitive functioning is similarly impaired. This recognition is considered a fundamental skill for successful social interaction. However, it is unclear whether the ability to recognize facial emotions is correlated with the cognitive deficits observed in BD.

Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met).

The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls.

Introduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls.

Material And Methods: Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus.

Number of manic episodes is associated with elevated DNA oxidation in bipolar I disorder.

Bipolar disorder (BD) is a major public health problem characterized by progressive functional impairment. A number of clinical variables have been associated with progression of the disease, most notably number of affective episodes and presence of psychotic symptoms, both of which correlate with greater cognitive impairment, lower response rates for lithium, and possibly lower levels of neurotrophic factors. Oxidative damage to cytosine and guanosine (8-OHdG) has been described as a modulator of DNA methylation, but the extent of DNA oxidative damage involvement in BD remains unclear.

Association of the COMT Met¹⁵⁸ allele with trait impulsivity in healthy young adults.

Dopamine (DA) is considered to be an important neurotransmitter in the control of impulsive behavior, however, its underlying mechanisms have not been fully elucidated. Catechol-O-methyltransferase (COMT) is a key enzyme in the catabolism of DA within the prefrontal cortex (PFC) and has been suggested to play a role in the mediation of impulsive behavior. The COMT single nucleotide polymorphism (SNP) rs4680 (Val158Met) Met allele has been shown to decrease COMT enzyme activity and is associated with improved PFC cognitive function (intelligence and executive functions).

Bcl-2 rs956572 polymorphism is associated with increased anterior cingulate cortical glutamate in euthymic bipolar I disorder.

B-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca(2+)) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells.

Burden of maternal bipolar disorder on at-risk offspring: a controlled study on family planning and maternal care.

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects.

Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses.

COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder.

Objective: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients.

Does BDNF genotype influence creative output in bipolar I manic patients?

Introduction: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD.

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls.

Introduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression.