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Interviews were conducted with 336 mother--child dyads (children's ages ranged from 6 to 17 years; mothers' ages ranged from 20 to 59 years) in China, India, Italy, Kenya, the Philippines, and Thailand to examine whether normativeness of physical discipline moderates the link between mothers' use of physical discipline and children's adjustment. Multilevel regression analyses revealed that physical discipline was less strongly associated with adverse child outcomes in conditions of greater perceived normativeness, but physical discipline was also associated with more adverse outcomes regardless of its perceived normativeness. Countries with the lowest use of physical discipline showed the strongest association between mothers' use and children's behavior problems, but in all countries higher use of physical discipline was associated with more aggression and anxiety.

Exposure to severe stress can lead to the development of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The cause of PTSD is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and an imbalance of monoamines. Fruits and vegetables contain large amounts of luteolin (LU; 3′,4′,5,7-tetrahydroxylflavone), which has various pharmacological activities such as anti-inflammatory, antioxidant, and anti-allergic effects. We investigated the effects of LU on fear, depression, and anxiety following monoamine imbalance and hyperactivation of the HPA axis in rats exposed to single prolonged stress (SPS). Male rats were dosed with LU (10 and 20 mg/kg) once daily for 14 days after exposure to SPS. Administration of LU reduced fear freezing responses to extinction recall and depression- and anxiety-like behaviors, and suppressed increases in plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of LU restored the increased norepinephrine and decreased serotonin levels in the structures within the fear circuit, medial prefrontal cortex, and hippocampus. Our results showed that administration of LU improved freezing behavior according in a situation-dependent manner, and showed anti-depressant and anxiolytic effects. Thus, LU may be a useful therapeutic agent to prevent traumatic stress such as PTSD.

Neuroinflammation is considered a major factor in several neuropsychiatric disorders. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including antiinflammatory, antioxidative, and protective properties. The present study was performed to examine whether GPS shows anxiolytic-like effects in a model of chronic inflammation induced by injection of lipopolysaccharide (LPS) into the rat hippocampus. The effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Introduction of LPS into the lateral ventricle caused inflammatory reactions and anxiety-like symptoms in the rats. Daily treatment with GPS (25, 50, and 100 mg/kg) for 21 consecutive days significantly increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. Moreover, GPS administration significantly reduced the freezing response to contextual fear conditioning, and significantly decreased the levels of proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB), levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of Toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA levels. Taken together, these results suggest that GPS may have anxiolytic-like effects and may have novel therapeutic potential for anxiety-like behaviors caused by neuroinflammation. GPS may be useful for developing an agents for the treatment of neuropsychiatric disorders, such as anxiety, due to its antiinflammatory activities and the modulation of NF-κB/iNOS/TLR4/BDNF.

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70 mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD.

Exposure to severe stress can lead to the development of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The cause of PTSD is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and an imbalance of monoamines. Fruits and vegetables contain large amounts of luteolin (LU; 3′,4′,5,7-tetrahydroxylflavone), which has various pharmacological activities such as anti-inflammatory, antioxidant, and anti-allergic effects. We investigated the effects of LU on fear, depression, and anxiety following monoamine imbalance and hyperactivation of the HPA axis in rats exposed to single prolonged stress (SPS). Male rats were dosed with LU (10 and 20 mg/kg) once daily for 14 days after exposure to SPS. Administration of LU reduced fear freezing responses to extinction recall and depression- and anxiety-like behaviors, and suppressed increases in plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of LU restored the increased norepinephrine and decreased serotonin levels in the structures within the fear circuit, medial prefrontal cortex, and hippocampus. Our results showed that administration of LU improved freezing behavior according in a situation-dependent manner, and showed anti-depressant and anxiolytic effects. Thus, LU may be a useful therapeutic agent to prevent traumatic stress such as PTSD. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a stress-related psychiatric or mental disorder characterized by experiencing a traumatic stress. The cause of such PTSD is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and imbalance of monoamines. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. We investigated the effects of MYR on fear, depression, and anxiety following monoamine imbalance and hyperactivation of HPA axis in rats exposed to a single prolonged stress (SPS). Male rats were dosed with MYR (10 and 20 mg/kg, i.p.) once daily for 14 days after exposure to SPS. Administration of MYR reduced freezing responses to extinction recall, depression, and anxiety-like behaviors and decreased increase of plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of MYR restored decreased serotonin and increased norepinephrine in the fear circuit regions, medial prefrontal cortex, and hippocampus. It also increased the reduction in the brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B mRNA expression and the ratio of p-ERK/extracellular signal-regulated kinase (ERK) in the hippocampus. Thus, MYR exerted antidepressant and anxiolytic effects by regulation of HPA axis and activation of the BDNF-ERK signaling pathway. Finally, we suggest that MYR could be a useful therapeutic agent to prevent traumatic stress such as PTSD. [ABSTRACT FROM AUTHOR]

Recently, neuroinflammation is thought to be one of the important causes of many neuropsychiatric diseases. Quercetin (QUER) is a natural flavonoid, and it is well known that QUER has antioxidative, anti-inflammatory, and neuroprotective effects. In our study, lipopolysaccharide (LPS) was injected into the lateral ventricle of rats to induce anxiety-like behaviors and neuroinflammation, and it was confirmed that chronic administration of QUER could improve anxiety-like symptoms. We also investigated the effects of QUER on inflammatory markers and its major mechanisms associated with inflammation in the hippocampus. Daily administration of QUER (10, 50, and 100 mg/kg) daily for 21 days significantly improved anxiety-like behaviors in the elevated plus-maze test and open field test. QUER administration significantly reduced inflammatory markers such as interleukin-6, interleukin-1β, cyclooxygenase-2, and nuclear factor-kappaB levels in the brain. In addition, QUER significantly increased the brain-derived neurotrophic factor (BDNF) mRNA level and decreased the nitric oxide synthase (iNOS) mRNA level. Therefore, our results have shown that QUER can improve anxiety-like behaviors caused by chronic neuroinflammation. This anxiolytic effect of QUER has been shown to be due to its anti-inflammatory effects and appropriate regulation of BDNF and iNOS expression. Thus, QUER provides the potential as a therapeutic agent to inhibit anxiety-like symptoms in neuropsychiatric diseases, such as anxiety. [ABSTRACT FROM AUTHOR]

Neuroinflammation is considered a major factor in several neuropsychiatric disorders. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including antiinflammatory, antioxidative, and protective properties. The present study was performed to examine whether GPS shows anxiolytic-like effects in a model of chronic inflammation induced by injection of lipopolysaccharide (LPS) into the rat hippocampus. The effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Introduction of LPS into the lateral ventricle caused inflammatory reactions and anxiety-like symptoms in the rats. Daily treatment with GPS (25, 50, and 100 mg/kg) for 21 consecutive days significantly increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. Moreover, GPS administration significantly reduced the freezing response to contextual fear conditioning, and significantly decreased the levels of proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB), levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of Toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA levels. Taken together, these results suggest that GPS may have anxiolytic-like effects and may have novel therapeutic potential for anxiety-like behaviors caused by neuroinflammation. GPS may be useful for developing an agents for the treatment of neuropsychiatric disorders, such as anxiety, due to its antiinflammatory activities and the modulation of NF-κB/iNOS/TLR4/BDNF. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a trauma-induced psychiatric disease characterized by impaired hyperarousal, fear extermination, depression, anxiety, and amnesic symptoms that may include the release of monoamines in the dread circuit. Curcumin (CUR), a major diarylheptanoid and polyphenolic component of Curcuma longa, reportedly possesses several pharmacological features, including antidiabetic, antiatherosclerotic, anticancer, and neuropsychiatric actions. But the anxiolytic-like effects of CUR and its mechanism of action in PTSD are unclear. The current research measured some anxiety-related behavioral responses to examine the effects of CUR on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) dysfunction. Rats received CUR (20, 50, or 100 mg/kg, i.p., once daily) for 14 days after SPS exposure. Administration of CUR significantly increased the number of central zone crossings in the open field test and reduced grooming behavior in the elevated plus maze (EPM) test and increased the number of open-arm visits on the EPM test. CUR administration significantly reduced freezing response to contextual fear conditioning. CUR recovered neurochemical abnormalities and SPS-induced decreased 5-HT tissue levels in the hippocampus, amygdala, and striatum. These results suggested that CUR has anxiolytic-like effects on biochemical and behavioral symptoms associated with anxiety. Thus, CUR may be a useful agent to alleviate or treat psychiatric disorders similar to those observed in patients with PTSD. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70 mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-a, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain. [ABSTRACT FROM AUTHOR]

Background: Repeated injection of corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. We examined the effects of Angelica gigas extract (AGN) treatment in a rat model of depressive and anxiety-like behaviors, induced by chronic CORT exposure. Methods: Male rats received 10, 20, or 50 mg/kg AGN (i.p.) 30 min prior to a daily injection of CORT for 21 consecutive days. Activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotropin-releasing factor in the hypothalamus. Results: Daily AGN administration significantly reversed the depression and anxiety-like behavioral abnormalities. It also blocked increases in tyrosine hydroxylase expression in the locus coeruleus, and suppressed the decreased expression levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB mRNAs in the hippocampus. Conclusions: These findings indicate that administration of AGN prior to high-dose exogenous CORT significantly improved helpless behaviors, possibly by modulating the central noradrenergic system and regulation of BDNF expression in rats. Thus, AGN may be a useful agent for the treatment or alleviation of psychiatric disorders associated with depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: Repeated injection of corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. We examined the effects of Angelica gigas extract (AGN) treatment in a rat model of depressive and anxiety-like behaviors, induced by chronic CORT exposure. Methods: Male rats received 10, 20, or 50 mg/kg AGN (i.p.) 30 min prior to a daily injection of CORT for 21 consecutive days. Activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotropin-releasing factor in the hypothalamus. Results: Daily AGN administration significantly reversed the depression and anxiety-like behavioral abnormalities. It also blocked increases in tyrosine hydroxylase expression in the locus coeruleus, and suppressed the decreased expression levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB mRNAs in the hippocampus. Conclusions: These findings indicate that administration of AGN prior to high-dose exogenous CORT significantly improved helpless behaviors, possibly by modulating the central noradrenergic system and regulation of BDNF expression in rats. Thus, AGN may be a useful agent for the treatment or alleviation of psychiatric disorders associated with depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

The pathophysiology underlying anxiety disorders involves stress and associated increases in glucocorticoid levels in the blood. The present study investigated the effects of the administration of the crude extract ofPolygala tenuifolia(EPT) on repeated restraint stress–induced anxiety-like behavioral responses in mice. Additionally, possible changes in the central noradrenergic and brain-derived neurotrophic factor (BDNF)–signaling systems were assessed in the hippocampus of these mice. For 14 consecutive days, mice were orally administrated EPT (50 or 250 mg/kg) 30 min prior to the restraint stress procedure (2 h/day). Dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis in response to the repeated restraint stress was confirmed by measuring serum levels of corticosterone and the expression of corticotrophin-releasing factor in the hypothalamus. Compared with control subjects, the daily administration of higher doses of EPT (250 mg/kg) increased open-arm exploration in an elevated plus maze and the total number of line crossings in an open-field test. EPT also reversed the increased expression of tyrosine hydroxylase in the locus coeruleus and the decreased expression of BDNF mRNA in the hippocampus. Together, these findings demonstrate that the administration of EPT prior to repeated restraint stress significantly reduced anxiety-like behaviors in mice. These changes were associated with a modification of the central noradrenergic system and the upregulation of BDNF expression, which in turn attenuated activity in the HPA axis. [ABSTRACT FROM PUBLISHER]

We investigated the anxiolytic-like activity of a -asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety. [ABSTRACT FROM AUTHOR]

Background Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression. Aims To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome. Method A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ≤7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome. Results The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit. Conclusions We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate whether acupuncture stimulation attenuates withdrawal-induced behaviors in the rats during protracted abstinence following chronic morphine exposure. To do this,male rats were first exposed to morphine gradually from 20 to 100mg/kg for 5 days, and subsequently naloxone was injected once to extend despair-related withdrawal behaviors for 4 weeks. Acupuncture stimulation was performed once at the SP6 (Sanyinjiao) acupoint on rat's; hind leg for 5min during protracted abstinence from morphine. The acupuncture stimulation significantly decreased despair-like behavior deficits in the forced swimming test and low sociability in the open-field test as well as increased open-arm exploration in the elevated plus maze test in the last week of 4-week withdrawal period. Also the acupuncture stimulation significantly suppressed the increase in the hypothalamic corticotropin-releasing factor (CRF) expression, the decrease in the tyrosine hydroxylase expression in the locus coeruleus, and the decrease in the hippocampal brain-derived neurotrophic factor mRNA expression, induced by repeated injection of morphine. Taken together, these findings demonstrate that the acupuncture stimulation of SP6 significantly reduces withdrawal-induced behaviors, induced by repeated administration of morphine in rats, possibly through the modulation of hypothalamic CRF and the central noradrenergic system. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder characterized by impaired fear extinction, depression, and anxiety caused by dysregulation of the hypothalamic–pituitary–adrenal axis and an imbalance of monoamines. Protocatechuic acid (PCA; 3,4-dihydroxybenzoic acid), a major polyphenol metabolite, has various pharmacological effects, such as anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. In this study, the efficacy of PCA for fear extinction, antidepressant, and anxiolytic effects in PTSD-mediated psychiatric disorders, were evaluated by exposing rats to single prolonged stress (SPS). Male rats were administered PCA (100 or 200 mg/kg) once daily for 14 days after exposure to SPS. PCA significantly decreased situational fear, depressive and anxiety-like behaviors, and corticosterone levels. In addition, PCA regulated the imbalance of serotonin and norepinephrine in the fear circuit region (i.e., the medial prefrontal cortex and hippocampus [Hipp]), and suppressed the decrease in brain-derived neurotrophic factor mRNA expression in the Hipp. The results showed that PCA administration improves freezing behavior and has antidepressant and anti-anxiety effects through modulation of the serotonergic nervous system and monoamines in rats. These results indicated that PCA may be useful as a food ingredient to prevent PTSD. [ABSTRACT FROM AUTHOR]