The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels.

Exercise is known to have beneficial effects on cognition, mood, and the brain. However, exercise also activates the hypothalamic-pituitary-adrenal axis and increases levels of the glucocorticoid cortisol (CORT). CORT, also known as the "stress hormone," is considered a mediator between chronic stress and depression and to link various cognitive deficits.

Confirmation of the factorial structure of the Japanese short version of the TEMPS-A in psychiatric patients and general adults.

Background: The Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) is a 110-item questionnaire that assesses five affective temperaments. However, a valid shortened version is desired for large-scale investigations to enhance the compliance of respondents.

Methods: A confirmatory factor analysis was conducted among 320 psychiatric patients and 61 general adults.

Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically.

Although preclinical and clinical studies have established the efficacy of lithium augmentation of antidepressant drugs, the mechanism of action of lithium augmentation is not fully understood. Our previous study reported that subchronic lithium treatment enhanced the anxiolytic-like effect of systemic mirtazapine. In the present study, we examined the effect of subchronic lithium in combination with acute local intracerebral injection of mirtazapine on fear-related behaviors in a contextual fear conditioning test in rats to clarify the target brain region of lithium augmentation of mirtazapine.

Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats.

The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect.

The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise.

Despite the well-documented beneficial effect of exercise on stress coping and depression treatment, its underlying neurobiological mechanism remains unclear. This is further complicated by a 'side effect' of exercise: it increases basal glucocorticoid (CORT), the stress hormone, which has been shown to be a mediator linking stress to depressive disorders. Here we show that three weeks of voluntary wheel running reduced rats' immobility in the forced swim test (FST), an antidepressant-like effect.

Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder.

Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse.

The moderator effects of affective temperaments, childhood abuse and adult stressful life events on depressive symptoms in the nonclinical general adult population.

Background: We recently demonstrated in the structural equation modeling that four of five affective temperaments, as measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire version (TEMPS-A), are strong mediators between childhood abuse and depressive symptoms in the nonclinical general adult population. In this study, we hypothesized that affective temperaments, childhood abuse, and adult life events have moderator effects that interact with one another on depressive symptoms. The hierarchical multiple regression analysis was used to analyze this interaction model.

Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear.

Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual fear conditioning test in rats, an animal model of anxiety or fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned fear.

Local infusion of citalopram into the basolateral amygdala decreased conditioned fear of rats through increasing extracellular serotonin levels.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive disorders and anxiety disorders. The anxiolytic mechanism of SSRIs is currently unclear. To investigate the anxiolytic effects of SSRIs, we measured both freezing behavior and extracellular serotonin and dopamine levels in the basolateral amygdala when rats were given conditioned fear stress under local reverse-dialysis of citalopram, an SSRI, into the basolateral amygdala.

Effect of the coadministration of citalopram with mirtazapine or atipamezole on rat contextual conditioned fear.

Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant, which blocks the α2-adrenergic autoreceptors and heteroreceptors, has shown anxiolytic properties in clinical trials and preclinical animal experiments. The addition of mirtazapine to selective serotonin reuptake inhibitors (SSRIs) is clinically suggested to be more effective for anxiety disorders. In this study, we examined the combined effects of mirtazapine and citalopram, an SSRI, on the freezing behavior of rats, which was induced by contextual conditioned fear as an index of anxiety or fear.

Anxiolytic-like effect of mirtazapine mediates its effect in the median raphe nucleus.

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), blocks the α2-adrenergic autoreceptors and heteroreceptors, which are responsible for controlling noradrenaline and 5-hydroxy-tryptamine (5-HT) release. Though preclinical and clinical studies have shown that mirtazapine exerts an anxiolytic action, its precise brain target sites remain unclear. In the present study, we investigated the brain area(s) in which mirtazapine exerts its anxiolytic-like effects on the expression of contextual conditioned freezing in rats.

The effect of dopamine on adult hippocampal neurogenesis.

Cumulative studies indicated that adult hippocampal neurogenesis might be involved in the action mechanism of antidepressant drugs and/or the pathophysiology of depression. Dopamine (DA) is involved in the regulation of motivation, volition, interest/pleasure, and attention/concentration, all of which are likely to be impaired in depressed patients. Several previous reports suggest that depression may often be accompanied by a relative hypo-dopaminergic state, and some DA receptor agonists are beneficial effects in the treatment for refractory and bipolar depression.

Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3β and β-catenin pathway.

Neurogenesis in the adult dentate gyrus (DG) is decreased in rodent models for mood disorders. Mood stabilizers including lithium (Li) and valproate (VPA) increase it. These increasing effects of Li and VPA on neurogenesis in adult DG are considered to be one of the therapeutic actions of Li and VPA, but their molecular mechanism remains unclear.

Selegiline remarkably improved stage 5 treatment-resistant major depressive disorder: a case report.

We report a case in which selegiline, an irreversible monoamine oxidase B (MAO-B) inhibitor, greatly improved depressive symptoms in an adult with stage 5 treatment-resistant major depressive disorder. Four antidepressants and four augmentation therapies had previously been ineffective or intolerable, and electroconvulsive therapy had only a temporary effect. After 20 weeks of treatment with selegiline (10 mg/day), the patient's score on the 17-item Hamilton Depression Rating Scale (HDRS) had decreased from 19 to 4 points.

Abnormalities in extracellular glycine and glutamate levels in the striatum of sandy mice.

Objective: Glycine regulates glutamatergic neurotransmission, and several papers have reported the relationship between glycine and schizophrenia. The dysbindin-1 (DTNBP1: dystrobrevin-binding protein 1) gene is related to glutamatergic neurotransmission and has been found to be a strong candidate gene for schizophrenia. In this study, we clarified the relationship between dysbindin, glutamate, and glycine with in vivo microdialysis methods.

Differences between bipolar and unipolar depression on Rorschach testing.

Background: The bipolar-unipolar distinction in patients with a major depressive episode is the most important issue related to the diagnosis and treatment of mood disorders, but remains unresolved. This study was undertaken to compare bipolar and unipolar depression on Rorschach testing using the Comprehensive System with reference to healthy Japanese controls.

Methods: Patients with bipolar or unipolar depression who had undergone the Rorschach test for routine clinical purposes were followed up naturalistically for a long period.

Development and validation of a screening questionnaire for present or past (hypo)manic episodes based on DSM-IV-TR criteria.

Background: We developed a self-reported questionnaire, the Manic Episode Screening Questionnaire (MES), based on the eight diagnostic criteria items of DSM-IV-TR (hypo)manic episodes. This study was designed to determine the optimal screening methods to identify bipolar disorders among mood disorder patients of a psychiatric specialty clinic.

Methods: In 95 mood disorder patients, we assessed the operational characteristics of the MES as a screening and diagnostic instrument using a DSM-IV-TR diagnosis by a trained psychiatrist as a reference standard.

Effect of triiodothyronine (T(3)) augmentation of acute milnacipran administration on monoamine levels: an in vivo microdialysis study in rats.

Background: Up to 30% of depressed patients are partially or totally resistant to antidepressant therapy. The administration of triiodothyronine (T(3)) to antidepressant nonresponders can be an effective augmentation strategy, although the mechanism is not fully understood.

Methods: In vivo microdialysis was used to examine the effect of T(3) augmentation of the antidepressant, milnacipran.

Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells.

Adult neurogenesis in dentate gyrus (DG) is involved in the action mechanism of mood stabilizers. However, it is poorly understood how mood stabilizers affect adult neurogenesis in DG. Neurogenesis consists of proliferation, survival (anti-apoptosis) and differentiation of neural precursor cells in adult DG.

SSRIs and conditioned fear.

Among drugs that act on serotonergic neurotransmission, selective serotonin (5-HT) reuptake inhibitors (SSRIs) are now the gold standard for the treatment of anxiety disorders. The precise mechanisms of the anxiolytic actions of SSRIs are unclear. We reviewed the literature related to the effects of SSRIs and the neurochemical changes of 5-HT in conditioned fear.

Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells.

Neurogenesis in the adult dentate gyrus (DG) is considered to be partly involved in the action of mood stabilizers. However, it remains unclear how mood stabilizers affect neural precursor cells in adult DG. We have established a culture system of adult rat DG-derived neural precursor cells (ADP) and have shown that lithium, a mood stabilizer, and dexamethasone, an agonist of glucocorticoid receptor, reciprocally regulate ADP proliferation.