Akkermansia muciniphila ameliorates depressive disorders in a murine alcohol-LPS (mALPS) model.

Depression is the most common mental disorder in the world. Recently, an increasing number of studies have reported alcohol-related depression. However, there is no simple, efficient, and time-saving alcohol-related depression animal model yet. Based on the fact that people with alcohol addiction often have impaired gastrointestinal (GI) tract health like dysbiosis, which serves as a primary factor to augment lipopolysaccharides (LPS), we first developed a murine alcohol-LPS model (mALPS), with oral gavage of LPS in acute alcohol treated mice, and successfully observed depression-like symptoms. We found that acute alcohol treatment damaged the intestinal barrier and caused dysbiosis, which further increased the translocation of LPS and neuroinflammatory responses (TNF-α and IL-1ß) and led to abnormal expression of the depression-related genes, i.e. BDND and IDO, reduced the levels of 5-HT and caused depressive behaviors in mice. Probiotic intervention could improve depressive symptoms without notable adverse effects. Akkermansia muciniphila (AKK), one of the next-generation probiotics, has been widely used for the restoration of the intestinal barrier and reduction of inflammation. Here, we found that AKK significantly ameliorated alcohol-related depressive behaviors in a mALPS model, through enhancing the intestinal barrier and maintaining the homeostasis of the gut microbiota. Furthermore, AKK reduced serum LPS, ameliorated neuroinflammation (TNF-α and IL-1ß), normalized the expression of depression-related genes and increased the 5-HT levels in the hippocampus. Our study suggests that AKK supplements will be a promising therapeutic regime for alcohol-associated depression in the future.

The Role of Natural Products in Treatment of Depressive Disorder.

Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's life. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic- pituitary-adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.

Protective effect of Myrcia pubipetala Miq. against the alterations in oxidative stress parameters in an animal model of depression induced by corticosterone.

Depression is a debilitating disorder in humans that significantly affects quality of life. As such, alternative therapies are highly sought after by patients seeking treatment for depression. Experimentally, the chronic administration of corticosterone (CORT) in rodents has been reported to promote depressive-like behaviors. Herein, animals received saline or CORT for 21 days and, during the last 7 days, they were treated with the crude hydroalcoholic extract (CHE) of Myrcia pubipetala Miq (50, 100 or 150 mg/Kg), or vehicle (distilled water), by oral route. After 24 h, animals were subjected to the open field (OFT) and forced swimming tests (FST), and then sacrificed for the removal of the hippocampus and cerebral cortex for biochemical analysis. Results showed enhanced catalase (CAT) and superoxide dismutase (SOD) activities, as well as an elevated formation of thiobarbituric acid reactive substances (TBARS), in the cerebral cortex of CORT-treated mice. The chronic administration of the CHE (100 and 150 mg/Kg) reduced TBARS and the increased total sulfhydryl content, and also reversed the increase in TBARS induced by CORT. In the hippocampus, CORT increased CAT and SOD activities and reduced glutathione peroxidase (GSH-Px) (C) activity, while Myrcia pubipetala Miq. CHE (100 and 150 mg/Kg) increased GSH-Px activity when administered alone and reversed decreased GSH-Px (100 and 150 mg/Kg) activity when given during CORT administration. Neither CORT administration nor CHE treatment significantly altered the immobility time of the animals in FST and no changes were observed in the locomotor activity of the animals in the OFT. Findings indicate that the CHE of Myrcia pubipetala Miq. exerts antioxidant effects in the cerebral cortex and hippocampus of mice induced to depression by CORT. Since phenolic compounds are reported to have antioxidant effects in this species, the effects of the CHE may be, at least in part, mediated by the presence of these compounds in Myrcia extract.

Ginsenoside Rk1 alleviates LPS-induced depression-like behavior in mice by promoting BDNF and suppressing the neuroinflammatory response.

Ginsenoside Rk1, a saponin component produced by heat-processed ginseng, possesses anti-inflammatory and antitumor activities. The aim of our study was to explore the effects of Rk1 on Lipopolysaccharide (LPS)-induced depression-like behavior in mice and to observe its effects on oxidative stress, the inflammatory response and brain-derived neurotrophic factor (BDNF) - tropomyosin-related kinase B (TrkB) signaling. After mice were pretreated with Rk1 (5, 10, and 20 mg/kg), the immobility time in both the forced swimming test (FST) and the tail suspension test (TST) was reduced, suggesting that Rk1 effectively improved depression-like symptoms. Rk1 (10 and 20 mg/kg) and Fluoxetine (Flu, 20 mg/kg) increased the activity of the antioxidant enzyme SOD in the brain and protected against lipid peroxidation. Different concentrations of Rk1 (10 and 20 mg/kg) and Flu significantly decreased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 in serum, while Rk1 (5, 10, and 20 mg/kg) and Flu reduced the concentrations of IL-6 in a dose-dependent manner. Western blot analysis showed that the administration of Rk1 (20 mg/kg) and Flu significantly downregulated the level of Sirt1 and that Rk1 (5, 10, and 20 mg/kg) and Flu inhibited the p-NF-κb/NF-κb and p-IκB-α/IκB-α ratios, which indicated that the neuroprotective effect of Rk1 may be related to the suppression of inflammation. In addition 5, 10 and 20 mg/kg Rk1 significantly attenuated the LPS-induced decreases in BDNF and TrkB. These results indicated that Rk1 acts as an antidepressant through its antioxidant activity, the inhibition of neuroinflammation, and the positive regulation of the BDNF-TrkB pathway. This study may help develop active ginsenoside-based compounds for neurodegenerative diseases.

Retinoic acid and depressive disorders: Evidence and possible neurobiological mechanisms.

The retinoid family members, including vitamin A and derivatives like 13-cis-retinoic acid (ITT) and all-trans retinoic acid (ATRA), are essential for normal functioning of the developing and adult brain. When vitamin A intake is excessive, however, or after ITT treatment, increased risks have been reported for depression and suicidal ideation. Here, we review pre-clinical and clinical evidences supporting association between retinoids and depressive disorders and discuss several possible underlying neurobiological mechanisms. Clinical evidences include case reports and studies from healthcare databases and government agency sources. Preclinical studies further confirmed that RA treatment induces hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and typical depressive-like behaviors. Notably, the molecular components of the RA signaling are widely expressed throughout adult brain. We further discuss three most important brain systems, hippocampus, hypothalamus and orbitofrontal cortex, as major brain targets of RA. Finally, we highlight altered monoamine systems in the pathophysiology of RA-associated depression. A better understanding of the neurobiological mechanisms underlying RA-associated depression will provide new insights in its etiology and development of effective intervention strategies.

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

PURPOSE OF REVIEW: This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use. RECENT FINDINGS: There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD. SUMMARY: The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

Factors associated with psychological distress amongst outpatient chemotherapy patients: An analysis of depression, anxiety and stress using the DASS-21.

AIM: This study sought to identify clinical, demographic and service-related factors associated with psychological distress amongst outpatient chemotherapy patients. BACKGROUND: Distress in cancer patients leads to increased risk of psychological comorbidity, contributing to sub-optimal treatment adherence and potentially leading to poorer health outcomes. Screening and recognition of distress and risk factors is an important aspect of holistic care within a multidisciplinary team environment. METHODS: Data were obtained via survey and chart review of ambulatory chemotherapy patients at three public tertiary referral hospitals in Perth, Western Australia. The DASS-21 was used to screen for psychological distress. Regression analyses were used to assess the relationship between distress and a range of cancer, socioeconomic and treatment factors. RESULTS: Patients with a Karnofsky Performance Score≤80 (OR 3.8, 95% CI [1.7, 78.7]) and average waiting time (between oncology outpatient appointment and commencement of chemotherapy infusion) >60min (OR 2.4, 95% CI [1.04, 5.5]) were at increased risk of moderate-severe distress. Patients with a household income between $AU 50-75,000 p.a. had a lower risk of distress compared to <$25,000 p.a. (OR 0.05, 95% CI [0.01, 0.52]). On sub-scale analysis, depression and anxiety contributed more to overall distress than the stress subscales. CONCLUSIONS: Performance status, waiting times and household income were key predictors of distress. Findings could assist clinicians to identify higher-risk population subsets that could benefit from targeted screening and additional psychological and social work support. Findings could also assist administrators to consider the contribution of modifiable factors such as waiting times to patient distress.

Sesquiterpenoids from the Root of Panax ginseng Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior through the Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase B and Sirtuin Type 1/Nuclear Factor-κB Signaling Pathways.

The previous study indicated sesquiterpenoids from the root of Panax ginseng (SPG) exhibited a significant antidepressant-like effect, which might be mediated by the modification of the dopaminergic, GABAergic, and glutamatergic systems. This study was to investigate antidepressant effects and mechanisms on the lipopolysaccharide (LPS)-induced depression-like behavior of SPG. In the tail suspension test (TST) and forced swimming test (FST), SPG (0.25 and 1 mg/kg, i.g.) and fluoxetine (20 mg/kg, i.p.) effectively reduced the immobility time. SPG treatment significantly reduced serum levels of IL-6 and TNF-α and increased suppressed superoxide dismutase (SOD) activity in the hippocampus. In addition, SPG effectively upregulated the brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), and sirtuin type 1 (Sirt 1) expression in the hippocampus and downregulated the inhibitor of κB-α (IκB-α) and nuclear factor-κB (NF-κB) phosphorylation. These results suggested that SPG exhibited an antidepressant-like effect through the BDNF/TrkB and Sirt 1/NF-κB signaling pathways.

Protective effect of Lycium Barbarum polysaccharides on dextromethorphan-induced mood impairment and neurogenesis suppression.

Dextromethorphan (DXM) is one of the common drugs abused by adolescents. It is the active ingredient found in cough medicine which is used for suppressing cough. High dosage of DXM can induce euphoria, dissociative effects and even hallucinations. Chronic use of DXM may also lead to depressive-related symptoms. Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of ageing-related neurodegenerative diseases. A recent study has shown the potential beneficial effect of Lycium barbarum to reduce depression-like behavior. In the present study, we investigated the role of Lycium barbarum polysaccharide (LBP) to alleviate DXM-induced emotional distress. Sprague Dawley rats were divided into 4 groups (n=6 per group), including the normal control (vehicles only), DXM-treated group (40 mg/kg DXM), LBP-treated group (1 mg/kg LBP) and DXM+ LBP-treated group (40 mg/kg DXM and 1 mg/kg LBP). After two-week treatment, the DXM-treated group showed increased depression-like and social anxiety-like behaviors in the forced swim test and social interaction test respectively. On the other hand, the adverse behavioral effects induced by DXM were reduced by LBP treatment. Histological results showed that LBP treatment alone did not promote hippocampal neurogenesis when compared to the normal control, but LBP could lessen the suppression of hippocampal neurogenesis induced by DXM. The findings provide insights for the potential use of wolfberry as an adjunct treatment option for alleviating mood disturbances during rehabilitation of cough syrup abusers.

The Role of Nitric Oxide in the Antidepressant Actions of 5-Aminoimidazole-4-Carboxamide-1-ß-D-Ribofuranoside in Insulin-Resistant Mice.

OBJECTIVE: Depression and Type 2 diabetes mellitus are interrelated conditions, but the underlying neurobiology is insufficiently understood. The current study compared the effects of a pharmacological manipulation with 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) that targets neurobiological processes by adenosine 5'-monophosphate-activated protein kinase activation versus exercise on depression-like behavior and nitric oxide (NO)-related measures. METHODS: A mouse model of a depression-like and insulin-resistant state, induced by the co-treatment of high-fat diet and corticosterone administration, was used to examine the antidepressant action of AICAR and exercise. RESULTS: Data showed that AICAR was a putative antidepressant in the depression-like and insulin-resistant mice (total ambulatory distance in the open-field test was 5120.69 ± 167.47 cm, mobility duration in the forced swim test was 17.61 ± 1.54 seconds, latency to feed in the novelty suppressed feeding test was 255.67 ± 37.80 seconds; all p values < .05). Furthermore, the antidepressant actions of AICAR required endothelial nitric oxide synthase activity with increased NO production in the prefrontal cortex, whereas corticosterone-induced expression of neuronal nitric oxide synthase and NO production may increase the risk of depression. In contrast to the traditional antidepressants such as ketamine and imipramine, AICAR interfered with the effects of insulin in skeletal muscle in the context of high-fat diet, consistent with the potential antidepressant effects of AICAR. Exercise also resulted in activation of adenosine 5'-monophosphate-activated protein kinase, nitric oxide synthase, and NO production (all p values < .01), which in turn may be implicated in the antidepressant effects of exercise. CONCLUSIONS: These findings suggest that NO is an essential signal mediating the antidepressant actions of AICAR. Ultimately, the concurrent effects of AICAR on brain insulin action and mitochondrial function suggest a potential of neural insulin resistance, which may contribute to our understanding of the comorbidity of depression and Type 2 diabetes.

[Coffee consumption in depressive disorders: it's not one size fits all]. / Consumo di caffè nei disturbi depressivi: una dose giusta, non per tutti.

Caffeine is considered the world's most popular psychoactive substance. Its actions on the central nervous system, mainly mediated by antagonism of adenosine receptors and subsequent modulation of dopaminergic activity, would be particularly sought by depressed patients, as an attempt of self-medication. However, published data suggested that coffee consumption may worsen psychopathological conditions in mood disorders. Thus, we reviewed available evidence in the literature that investigated the effects of coffee consumption on clinical development of underlying psychopathology. Literature research was done by typing on Medline/PubMed and PsychINFO the key words "coffee AND major depression", "coffee AND dysthymia". The research was limited to English language publications and to studies conducted exclusively on humans. Although literature data are conflicting, extensive follow-up studies indicate a significant caffeine effect on risk reduction of developing clinical depression symptoms. Clinical worsening was observed mainly in cases of postpartum depression and comorbid panic disorder. Taking in account the study limitations, we observed a biphasic profile in caffeine psychostimulant effect: low to moderate doses may correlate with a reduction in depressive risk in healthy subjects and an improvement of many clinical symptoms (attention, arousal, psychomotor performance) in depressed patients, whereas the assumption of high doses may result in thymic dysregulation, favor mixed affective states and worsen circadian profiles and anxiety symptoms.

Pycnogenol ameliorates depression-like behavior in repeated corticosterone-induced depression mice model.

Oxidative stress is considered to be a mechanism of major depression. Pycnogenol (PYC) is a natural plant extract from the bark of Pinus pinaster Aiton and has potent antioxidant activities. We studied the ameliorative effect of PYC on depression-like behavior in chronic corticosterone- (CORT-) treated mice for 20 days. After the end of the CORT treatment period, PYC (0.2 mg/mL) was orally administered in normal drinking water. Depression-like behavior was investigated by the forced swimming test. Immobility time was significantly longer by CORT exposure. When the CORT-treated mice were supplemented with PYC, immobility time was significantly shortened. Our results indicate that orally administered PYC may serve to reduce CORT-induced stress by radical scavenging activity.

Effect of prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on activity of proline-specific peptidases in brain structures of rats with experimental MPTP-induced depressive syndrome.

A noncompetitive synthetic inhibitor of prolyl endopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine (1.0 mg/kg intraperitoneally for 2 weeks) prevented the increase in activity of prolyl endopeptidase in the frontal cortex, striatum, and hypothalamus and activation of dipeptidyl peptidase IV in the frontal cortex of rats with experimental dopamine deficiency-dependent depressive syndrome caused by administration of proneurotoxin MPTP (2 weeks). Our results suggest that the antidepressive effect of prolyl endopeptidase inhibitor is at least partly related to prevention of enzyme activation in the frontal cortex. The antistress effect of this substance can be associated with prevention of enzyme activation in the hypothalamus.

Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy.

Many symptoms of neurologic or psychiatric illness--such as cognitive impairment, depression, anxiety, attention deficits, and migraine--occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.

A biopsychosocial model of interferon-alpha-induced depression in patients with chronic hepatitis C infection.

BACKGROUND: The aim of this prospective study was to gain a more comprehensive picture of the biopsychosocial effects of interferon-α (IFN-α) treatment of patients with chronic hepatitis C (HCV). The predictors of depressive development and changes in health-related quality of life, life satisfaction and cognitive ability were measured with the inclusion of the social context. Furthermore, the effects of IFN-α treatment on indoleamine 2,3-dioxygenase, the level of tryptophan supply in the brain, the development of neurotoxic kynurenine metabolites and the thyroid glands were investigated. Therefore, for the first time the conditions for the development of depressive episodes in HCV patients treated with IFN-α were examined over the entire period of treatment as well as 3 months later, applying a holistic biopsychosocial model. METHOD: Psychiatric and biological assessments were carried out at 6 different times: before, during (at 1, 3, 6 and 9 months) and after the end of IFN-α treatment. RESULTS: During IFN-α treatment 22 (53.7%) of 41 patients fulfilled the criteria for a treatment-related depressive disorder at least once during treatment. Contributing factors are tryptophan depletion (tryptophan to competing amino acids quotient), increased neurotoxic challenge (kynurenine to kynurenic acid quotient), less social support, female gender, preexisting psychiatric vulnerability, means of transmission, low financial security, impaired sexual satisfaction, small circle of friends, impaired physical role, strong body pain, low general health and vitality, reduced social functioning, impaired mental health and impaired emotional role. CONCLUSIONS: The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies.

Distress, coping, and drug law enforcement in a series of patients using medical cannabis.

Patients using medical cannabis in the United States inhabit a conflicting medicolegal space. This study presents data from a dispensary-based survey of patients using medical cannabis in the state of Washington regarding cannabis-specific health behaviors, levels of psychological distress, stress regarding marijuana criminality, past experiences with drug law enforcement, and coping behaviors. Thirty-seven subjects were enrolled in this study, and all but three completed survey materials. The median index of psychological distress, as measured by the Behavioral Symptom Inventory, was nearly 2.5 times higher than that found in a general population sample but one third less than that found in an outpatient sample. The subjects reported a moderate amount of stress related to the criminality of marijuana, with 76% reporting previous exposure to 119 separate drug law enforcement tactics in total. The subjects reported a wide range of coping methods, and their responses to a modified standardized survey showed the confounding influence of legality in assessing substance-related disorders.

Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study.

BACKGROUND: Adolescent major depressive disorder (MDD) is a life-threatening brain disease with limited interventions. Treatment resistance is common, and the illness burden is disproportionately borne by females. 31-Phosphorus magnetic resonance spectroscopy ((31)P MRS) is a translational method for in vivo measurement of brain energy metabolites. METHODS: We recruited 5 female adolescents who had been on fluoxetine (Prozac®) for ≥ 8 weeks, but continued meet diagnostic criteria for MDD with a Children's Depression Rating Scale-Revised (CDRS-R) raw score ≥ 40. Treatment response was measured with the CDRS-R. (31)P MRS brain scans were performed at baseline, and repeated following adjunctive creatine 4 g daily for 8 weeks. For comparison, 10 healthy female adolescents underwent identical brain scans performed 8 weeks apart. RESULTS: The mean CDRS-R score declined from 69 to 30.6, a decrease of 56%. Participants experienced no Serious Adverse Events, suicide attempts, hospitalizations or intentional self-harm. There were no unresolved treatment-emergent adverse effects or laboratory abnormalities. MDD participants' baseline CDRS-R score was correlated with baseline pH (p=0.04), and was negatively correlated with beta-nucleoside triphosphate (ß-NTP) concentration (p=0.03). Compared to healthy controls, creatine-treated adolescents demonstrated a significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up (31)P MRS brain scans. LIMITATIONS: Lack of placebo control; and small sample size. CONCLUSIONS: Further study of creatine as an adjunctive treatment for adolescents with SSRI-resistant MDD is warranted.

Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission.

The pathophysiological neural mechanism underlying the depressogenic and anxiogenic effects of chronic adolescent cannabinoid use may be linked to perturbations in monoaminergic neurotransmission. We tested this hypothesis by administering the CB(1) receptor agonist WIN55,212-2, once daily for 20 days to adolescent and adult rats, subsequently subjecting them to tests for emotional reactivity paralleled by the in vivo extracellular recordings of serotonergic and noradrenergic neurons. Chronic adolescent exposure but not adult exposure to low (0.2 mg/kg) and high (1.0 mg/kg) doses led to depression-like behaviour in the forced swim and sucrose preference test, while the high dose also induced anxiety-like consequences in the novelty-suppressed feeding test. Electrophysiological recordings revealed both doses to have attenuated serotonergic activity, while the high dose also led to a hyperactivity of noradrenergic neurons only after adolescent exposure. These suggest that long-term exposure to cannabinoids during adolescence induces anxiety-like and depression-like behaviours in adulthood and that this may be instigated by serotonergic hypoactivity and noradrenergic hyperactivity.

Depression in methadone maintenance treatment patients: rate and risk factors.

BACKGROUND: Depression is widely prevalent among former heroin addicts in methadone maintenance treatment (MMT). The risk factors for depression among MMT patients that have not been well characterized, was studied. METHODS: In a cross-sectional study (January, 2004-August, 2005), 90 MMT patients were evaluated for depression by the 21-item Hamilton Rating Scale for Depression (21-HAM-D) and the Brief Psychiatric Rating scale (BPRS). To study possible induction of depression by drug abuse, urine samples tested for opiates, cocaine metabolite (benzoylecgonine), benzodiazepines (BDZ), cannabis (THC), amphetamines and methadone metabolite during 1 month preceding study entry: a drug was defined as being positive if at least one sample was positive. RESULTS: The 21-HAM-D and BPRS scores were significantly correlated (Pearson R=0.76, p<0.0005). Fifty percent were found to be suffering from depression (21-HAM-D, scored > or = 18). Fifteen new patients in MMT had better scores (5.1+/-5.7) than continuous patients (17.7+/-6.2, p<0.0005), independent of treatment duration. Higher scores were in 51 patients with any Axis I psychiatric diagnosis (18.9+/-5.7 vs. 11.4+/-7.9, p<0.0005), 74 abusing and or using prescribed BDZ (16.3+/-7.4 vs. 11.7+/-8, p=0.03), and 36 prescribed more than one type of medication (17.5+/-7.3 vs. 14.2+/-7.7, p=0.05). Females (N=40) had poorer scores than males (17.6+/-7 vs. 14.1+/-7.9, p=0.03), especially 12 admitted into treatment while pregnant (20.2+/-4.1). LIMITATION: Patient drug abuse and withdrawal could distort evaluation and lead to misclassification of depression. CONCLUSION: The major risk factors for depression were already being in MMT, female gender, any DSM-IV Axis I psychiatric diagnosis, taking any psychotropic medication, abuse or using prescribed BDZ, and methadone dose > 120 mg/day.

Activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats with dopamine deficiency-dependent MPTP-induced depressive syndrome.

The development of MPTP-induced depressive syndrome in rats was accompanied by activation of prolyl endopeptidase and dipeptidyl peptidase IV in the brain frontal cortex. Prolyl endopeptidase activity in the striatum also increased under these conditions. Our results indicate that proline-specific peptidases in the target structures of the brain dopaminergic system are involved in the pathogenesis of dopamine deficiency-dependent depressive states.