scholarly journals Second messenger/signal transduction pathways in major mood disorders: moving from membrane to mechanism of action, part II: bipolar disorder

CNS Spectrums ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 242-251 ◽  
Author(s):  
Mark J. Niciu ◽  
Dawn F. Ionescu ◽  
Daniel C. Mathews ◽  
Erica M. Richards ◽  
Carlos A. Zarate
Keyword(s):  
Signal Transduction ◽  
Bipolar Disorder ◽  
Mood Disorders ◽  
Second Messenger ◽  
Pharmacological Interventions ◽  
Major Depressive ◽  
The Past ◽  
Kinase C ◽  
Gsk 3Β ◽  
Intracellular Mediators

In this second of two articles on second messenger/signal transduction cascades in major mood disorders, we will review the evidence in support of intracellular dysfunction and its rectification in the etiopathogenesis and treatment of bipolar disorder (BD). The importance of these cascades is highlighted by lithium's (the gold standard in BD psychopharmacology) ability to inhibit multiple critical loci in second messenger/signal transduction cascades including protein kinase C (involved in the IP3/PIP2 pathway) and GSK-3β (canonically identified in the Wnt/Fz/Dvl/GSK-3β cascade). As a result, and like major depressive disorder (MDD), more recent pathophysiological studies and rational therapeutic targets have been directed at these and other intracellular mediators. Even in the past decade, intracellular dysfunction in numerous neuroprotective/apoptotic cascades appears important in the pathophysiology and may be a future target for pharmacological interventions of BD.

scholarly journals Second messenger/signal transduction pathways in major mood disorders: moving from membrane to mechanism of action, part I: major depressive disorder

CNS Spectrums ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 231-241 ◽  
Author(s):  
Mark J. Niciu ◽  
Dawn F. Ionescu ◽  
Daniel C. Mathews ◽  
Erica M. Richards ◽  
Carlos A. Zarate
Keyword(s):  
Signal Transduction ◽  
Major Depressive Disorder ◽  
Amino Acid ◽  
Depressive Disorder ◽  
Mood Disorders ◽  
Mechanism Of Action ◽  
Time Lag ◽  
Second Messenger ◽  
Mood Stabilizers ◽  
Major Depressive

The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in support of intracellular mediators in the pathophysiology and treatment of preclinical models of despair and major depressive disorder (MDD). More specifically, we will focus on the following pathways: cAMP/PKA/CREB, neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3β, and NFκB/ΔFosB. We will also discuss recent discoveries with rapidly acting antidepressants, which activate the mammalian target of rapamycin (mTOR) and release of inhibition on local translation via elongation factor stimulation. Throughout this discourse, we will highlight potential intracellular targets for therapeutic intervention. Finally, future clinical implications are discussed.

Adenylyl Cyclase Activity and Mood Disorders: Preliminary Data in Human Brain Postmortem

CNS Spectrums ◽  
1998 ◽  
Vol 3 (10) ◽  
pp. 70-75
Author(s):  
Lionella Palego ◽  
Annalisa Giromella ◽  
Maria Rosa Mazzoni ◽  
Antonio Giuseppe Naccarato ◽  
Donatella Marazziti
Keyword(s):  
Human Brain ◽  
Adenylyl Cyclase ◽  
Mood Disorders ◽  
Present Article ◽  
Preliminary Data ◽  
Second Messenger ◽  
Cyclase Activity ◽  
Adenylyl Cyclase Activity ◽  
The Past ◽  
Second Messenger Pathways

AbstractDuring the past decade, an increasing interest has been shifted from the study of neuroreceptors to their links with second-messenger pathways. In the present article, we shall briefly review the methodological tools for evaluating adenylyl cyclase activity in several human brain and peripheral models, as well as the studies suggesting its involvement in the pathophysiology of mood disorders. We shall present also some preliminary data obtained in our laboratory providing evidence for the measurement of serotonin-sensitive adenylyl cyclase activity in human brain postmortem.

scholarly journals Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder

2017 ◽  
Vol 2017 ◽  
pp. 1-37 ◽  
Author(s):  
Cristy Phillips
Keyword(s):  
Physical Activity ◽  
Bipolar Disorder ◽  
Mood Disorders ◽  
Biogenic Amine ◽  
Clinical Utility ◽  
Major Depressive ◽  
Positive Effects ◽  
Mental Diseases

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers.

scholarly journals EEG Frontal Asymmetry in Dysthymia, Major Depressive Disorder and Euthymic Bipolar Disorder

Symmetry ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2414
Author(s):  
Chiara Spironelli ◽  
Francesca Fusina ◽  
Marco Bortolomasi ◽  
Alessandro Angrilli
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mood Disorders ◽  
Quantitative Eeg ◽  
Beta Activity ◽  
Major Depressive ◽  
Eeg Asymmetry ◽  
Frontal Asymmetry ◽  
Frontal Eeg Asymmetry

In the last few decades, the incidence of mood disorders skyrocketed worldwide and has brought an increasing human and economic burden. Depending on the main symptoms and their evolution across time, they can be classified in several clinical subgroups. A few psychobiological indices have been extensively investigated as promising markers of mood disorders. Among these, frontal asymmetry measured at rest with quantitative EEG has represented the main available marker in recent years. Only a few studies so far attempted to distinguish the features and differences among diagnostic types of mood disorders by using this index. The present study measured frontal EEG asymmetry during a 5-min resting state in three samples of patients with bipolar disorder in a Euthymic phase (EBD, n = 17), major depressive disorder (MDD, n = 25) and persistent depressive disorder (PDD, n = 21), once termed dysthymia. We aimed to test the hypothesis that MDD and PDD lack the typical leftward asymmetry exhibited by normal as well as EBD patients, and that PDD shows greater clinical and neurophysiological impairments than MDD. Clinical scales revealed no symptoms in EBD, and significant larger anxiety and depression scores in PDD than in MDD patients. Relative beta (i.e., beta/alpha ratio) EEG asymmetry was measured from lateral frontal sites and results revealed the typical greater left than right frontal beta activity in EBD, as well as a lack of asymmetry in both MDD and PDD. The last two groups also had lower bilateral frontal beta activity in comparison with the EBD group. Results concerning group differences were interpreted by taking into account both the clinical and the neurophysiological domains.

Important Issues in Understanding Comorbidity Between Generalized Anxiety Disorder and Major Depressive Disorder

2014 ◽  
Author(s):  
Susan Mineka ◽  
Deepika Anand ◽  
Jennifer A. Sumner
Keyword(s):  
Major Depressive Disorder ◽  
Anxiety Disorder ◽  
Depressive Disorder ◽  
Mood Disorder ◽  
Mood Disorders ◽  
Generalized Anxiety Disorder ◽  
Generalized Anxiety ◽  
Major Depressive ◽  
Cross Sectional ◽  
The Past

The comorbidity of anxiety and mood disorders has been of great interest to psychopathology researchers for the past 25 years. One topic––the comorbidity of generalized anxiety disorder (GAD) and major depressive disorder (MDD)––has received considerable attention, in part because it has raised fundamental nosological issues regarding whether GAD should continue to be categorized as an anxiety disorder or whether it should be recategorized as a mood disorder. We review the logic for reclassifying GAD with the mood disorders as well as what we believe to be even more compelling reasons for why it should be retained as an anxiety disorder. In doing so, we review three different kinds of comorbidity—cross-sectional, cumulative (lifetime), and sequential. We also discuss overlaps and distinctions in what is known about the etiology of GAD and MDD and how their somewhat different cognitive and affective profiles bear on these issues of classification. Finally, we briefly discuss what some of the treatment implications may be for individuals with comorbid GAD and MDD.

scholarly journals Comparison of Sexual Experience and Behavior between Bipolar Outpatients and Outpatients without Mood Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jennifer Downey ◽  
Richard C. Friedman ◽  
Elizabeth Haase ◽  
David Goldenberg ◽  
Robinette Bell ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Sexual Behavior ◽  
Mood Disorders ◽  
Risky Sexual Behavior ◽  
Comparison Group ◽  
Sexual Experience ◽  
Sex Partners ◽  
Affective Illness ◽  
The Past ◽  
And Behavior

Sexual behavior over the past year of 32 outpatients with Bipolar disorder is compared to that of 44 Comparison patients that had never had an episode of affective illness. Subjects were outpatients treated with drugs and psychotherapy in routine office practice. Differences in sexual behavior between the two groups as a whole were minimal, but meaningful differences emerged when subgroups were compared. Compared to control men, Bipolar men had had more partners in the last year and were more likely to have had sex without condoms. Compared to Bipolar females, Bipolar males had more sex partners, had more sex with strangers, and were more likely to have engaged in homosexual behavior. Even so, some patients in the Comparison group also had engaged in risky sexual behavior. They had failed to use condoms and had had sex with strangers and prostitutes during the previous year.

scholarly journals Age-Related Increase in the Number of Oligodendrocytes Is Dysregulated in Schizophrenia and Mood Disorders

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Victor Vostrikov ◽  
Natalya Uranova
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
White Matter ◽  
Depressive Disorder ◽  
Mood Disorders ◽  
Numerical Density ◽  
Major Depressive ◽  
Age Related ◽  
Related Increase

The postnatal maturation of the human prefrontal cortex is associated with substantial increase of number of oligodendrocytes. Previously, we reported decreased numerical density of oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. To gain further understanding of the role oligodendrocytes in pathogenesis of schizophrenia and mood disorders, we examined the effect of the age on the number of oligodendrocytes in the prefrontal cortex in schizophrenia, bipolar disorder, and major depressive disorder. We revealed the age-related increase in numerical density of oligodendrocytes in layer VI and adjacent white matter of BA10 and BA 9 in normal controls but not in schizophrenia, bipolar disorder, and major depressive disorder. The absence of normal increase in the number of oligodendrocytes in gray and white matter with age in schizophrenia and mood disorders suggests that age-related process of oligodendrocyte increase is dysregulated in schizophrenia and mood disorders.

scholarly journals The genetics of the mood disorder spectrum: genome-wide association analyses of over 185,000 cases and 439,000 controls

2018 ◽  
Author(s):  
Jonathan R. I. Coleman ◽  
Héléna A. Gaspar ◽  
Julien Bryois ◽  
Gerome Breen ◽  
◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Major Depression ◽  
Depressive Disorder ◽  
Mood Disorders ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Major Depressive ◽  
Genome Wide ◽  
Genome Wide Significance

AbstractBackgroundMood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders.MethodsTo clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424).ResultsSeventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder.ConclusionsThe mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

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