Психофармакологические тесты в диагностике аффективных расстройств

Таким образом, для выбора адекватной терапии приступов аффективных психозов необходимо понять структуру состояния больного, отражающую механизмы образования его синдрома. Для этой цели клинический метод успешно дополняется психофармакологическими тестами. Лечение аффективных и аффектив­но-бредовых больных (кроме маниакальных) целесообразно начи­нать с пробного терапевтического курса анксиолитиками (феназепамом, лепонексом) или с диазепамового теста. В зависимости от трансформации клинической картины, указывающей на основ­ное биологическое расстройство, на «блок», являющийся основой патологического состояния, в дальнейшем назначаются антиде­прессивные или энергизирующие препараты. Создается впечатление,  что сфера применения нейролептиков в терапии аффективных приступов должна быть весьма ограниченной рамками маниакаль­ных и маниакально-параноидных состояний, в комбинации с нормотимиками.

 Точилов В.А. - ОБ ИССЛЕДОВАНИИ СТРУКТУРЫ И ЛЕЧЕНИИ АФФЕКТИВНЫХ ПРИСТУПОВ

Отсутствие долгосрочной противотревожной эффективности потенцирования кветиапином в предварительном исследовании

Background

Comorbid anxiety symptoms,in patients with a primary anxiety disorder or a mood disorder, leads to poor patient outcomes and burdens the healthcare system. This pilot study evaluated the feasibility of extended-release quetiapine fumarate (quetiapine XR) for the treatment of patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms compared to a placebo, as an adjunct to antidepressant therapy.

Methods

Thirty-nine patients with a diagnosis of a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms were enrolled in this study. Patients with a stable dose of antidepressant therapy were randomized according to a 2:1 probability of receiving either quetiapine XR or a placebo adjunctive treatment for 8 weeks. The efficacy was assessed by the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression of severity (CGI-S) score at baseline, week 1, 4, and 8.

Results

A total of 35 patients were included in this intention-to treat (ITT) population for the efficacy analysis (quetiapine XR: 22 patients; placebo: 13 patients). At week 4, statistically significant differences were observed on both the HAM-A score (p = 0.003) and the CGI-S score (p = 0.025), favouring the quetiapine XR (-13.00 +/- 4.14) compared to placebo (-6.63 +/- 5.42). However, no statistically significant difference was observed between the two groups with regard to changes from the baseline to week 8 on the HAM-A score (p = 0.332) or the CGI-S score (p = 0.833).

Conclusions

Augmentation of antidepressant treatment with quetiapine XR did not result in clinical improvement according to the outcome measure of anxiety using the HAM-A and CGI-S scores at week 8, among the patients with either a primary anxiety disorder or a mood disorder with comorbid anxiety symptoms. However, treatment with quetiapine XR as an adjunct to antidepressant therapy appeared to provide a short-term benefit at 4 weeks. Further study is needed with a larger sample size, randomized controlled design and control of the dosage prescribed.

 Quetiapine fumarate augmentation for patients with a primary anxiety disorder or a mood disorder: a pilot study

Нарушения дыхания во сне и психиатрические расстройства

The mechanism(s) underlying the connection between SDB and psychiatric symptoms is a matter of debate. From a psychiatric perspective, one can conceptualize the relationship as stemming from a direct physiological consequence of the general medical condition (in this case, sleep deprivation and nocturnal hypoxia/hypercapnia). Therefore, the increased prevalence of depression with SDB would not be surprising given that such a relationship is seen in other diseases that produce hypoxia and impair quality of life (eg, chronic obstructive pulmonary disease). On the other hand, excessive sleepiness and fatigue as a result of sleep apnea produce significant social and personal problems and result in depression. Ishman and colleagues showed that the daytime sleepiness is a strong predictor of depressive symptoms in patients with SDB.

Sleep apnea and depression can be bridged conceptually by vital exhaustion. Vital exhaustion refers to a state characterized by elevated somatic and cognitive symptoms of depression without affective symptoms. Our group as well as others demonstrated that vital exhaustion profiles were affected in patients with SDB. Therefore, depressive manifestations in patients with sleep apnea may reflect the patients’ vital exhaustion, which differs dramatically from melancholic affective mood changes observed in more typical forms of depression and dysthymia. As such, depressive phenomena in patients who have sleep apnea should be more akin to depression secondary to chronic medical illness.

The Correlation Between Sleep-Disordered Breathing and Psychiatry 

Ответ на провокацию углекислым газом при социофобии и паническом расстройстве

The 35% carbon dioxide (CO2) challenge is a well-established model of panic. This study aimed to investigate 35% CO2 sensitivity in patients with social anxiety disorder (SAD) compared with patients with panic disorder (PD) and normal controls. First, a 35% CO2 challenge was conducted including 16 patients with generalized SAD, 16 with PD and 16 normal subjects. Outcome was assessed by a Visual Analogue Scale for Fear (VAS-F) and the Panic Symptom List (PSL). Second, meta-analyses of fear and panic scores were performed, including data from the present experiment and from previous 35% CO2 challenge studies in patients with SAD. The present 35% CO2challenge found equal increases in VAS-F and PSL in patients with SAD compared with normal controls, whereas the CO2 response in patients with PD was significantly stronger than in controls. The meta-analyses confirmed the experimental data from this study, and in addition showed an intermediate panic rate in SAD patients, in between that of normal controls and patients with PD. In conclusion, neither our experiment nor the meta-analyses found evidence for a similarly exaggerated 35% CO2 sensitivity in SAD and PD, suggesting that the pathogenesis of SAD is different from PD, although patients with SAD may be slightly more sensitive than non-anxious controls.

35% CO2 sensitivity in social anxiety disorder 

Психические расстройства при гипотиреозе и гипертиреозе

The symptoms and signs of hyperthyroidism resemble those of primary mental disorders. Overactivity of the adrenergic system caused by hyperthyroidism may explain the similarity between the clinical presentations of hyperthyroidism and mania or anxiety, as well as the precipitating role of hyperthyroidism in the development of mania or anxiety disorder. It may also explain the increased sense of well being often experienced in the early stages of hyperthyroidism.[20,21]

The relationship between hyperthyroidism and depression is less clear. Depression is usually linked to hypothyroidism, not to hyperthyroidism. However, prolonged hyperthyroidism might exhaust noradrenergic transmission and thus contribute to depression. Noradrenergic exhaustion might well occur in patients with hyperthyroidism who have bipolar disorder. In the initial phase of hyperthyroidism, thyroid hormone stimulation of the noradrenergic system may cause mania; later, when noradrenergic neurotransmission is exhausted, it may contribute to depression.[21]

Mental symptoms and disorders secondary to hyperthyroidism should be treated first by restoring euthyroidism. Most mental symptoms, including depression, usually resolve once euthyroidism has been regained. Treatment with beta-adrenergic antagonists alone may quickly relieve many symptoms, including mental symptoms, even if euthyroidism is not restored,[22] providing evidence that overactivity of the adrenergic system is largely responsible for mental symptoms in hyperthyroidism.

Thyroid deficits are frequently observed in bipolar patients, especially in women with the rapid cycling form of the disease.[24] Both subclinical hypothyroidism and subclinical hyperthyroidism increase the risk for Alzheimer's disease, especially in women.[25] However, most hypothyroid patients do not meet the criteria for a mental disorder.

A recent study evaluated brain glucose metabolism during T4 treatment of hypothyroidism. A reduction in depression and cognitive symptoms was associated with restoration of metabolic activity in brain areas that are integral to the regulation of mood and cognition.[26••]

In hypothyroidism, replacement therapy with T4 remains the treatment of choice and resolves most physical and psychological signs and symptoms in most patients. However, some patients do not feel entirely well despite doses of T4 that are usually adequate.[27] In T4-treated patients, it was found that reduced psychological well being is associated with occurrence of polymorphism in the D2 gene,[28••] as well as in the OATP1c1 gene.[29]

Thyroid hormone replacement with a combination of T4 and T3, in comparison with T4 monotherapy, improves mental functioning in some but not all hypothyroid patients,[30,31•] and most of the patients subjectively prefer combined treatment.[32] Two studies have evaluated whether D2 polymorphism is associated with changes in psychological well being after combined T4 and T3 treatment. One underpowered study[33] reported a trend toward improvement. In a second study[28••] involving a very large sample, D2 polymorphism was associated with improvement in psychological well being after T4 and T3 treatment.

Thyroid Disease and Mental Disorders: Cause and Effect or Only comorbidity?

Метирапон и психотравмирующие воспоминания

“Metyrapone is a drug that significantly decreases the levels of cortisol, a stress hormone that is involved in memory recall,” explained lead author Marie-France Marin, a doctoral student.

Manipulating cortisol close to the time of forming new memories can decrease the negative emotions that may be associated with them, the researchers said.

“The results show that when we decrease stress hormone levels at the time of recall of a negative event, we can impair the memory for this negative event with a long-lasting effect,” said Sonia Lupien, Ph.D., who directed the research.

The Drug Metyrapone to Erase Bad Memories?

Блокирование 5-HT7 рецепторов как потенциальный механизм быстрого антидепрессивного эффекта

Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT7) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT7 receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test. In vivo, 5-HT7 receptors negatively regulate the firing activity of dorsal raphe 5-HT neurons and become desensitized after long-term administration of fluoxetine. In contrast with fluoxetine, a 1-week treatment with SB-269970 did not alter 5-HT firing activity but desensitized cell body 5-HT autoreceptors, enhanced the hippocampal cell proliferation, and counteracted the depressive-like behavior in olfactory bulbectomized rats. Finally, unlike fluoxetine, early-life administration of SB-269970, did not induce anxious/depressive-like behaviors in adulthood. Together, these findings indicate that the 5-HT7 receptor antagonists may represent a new class of antidepressants with faster therapeutic action.

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

Особенности воздействия пароксетина тревожную и депрессивную симптоматику

This is rather remarkable. Everyone calls paroxetine "an antidepressant", yet at least in one important sense it works better against OCD and social anxiety than it does against depression!

In fact, is paroxetine an antidepressant at all? It works better on MADRS and very poorly on the HAMD; is this because the HAMD is a better scale of depression, and the MADRS actually measures anxiety or OCD symptoms?

That's a lovely neat theory... but in fact the HAMD-17 has two questions about anxiety, scoring 0-4 points each, so you can score up to 8 (or 12 if you count "hypochondriasis", which is basically health anxiety, so you probably should), out of a total maximum of 52. The MADRS has one anxiety item with a max score of 6 on a total of 60. So the HAMD is more "anxious" than the MADRS.

This is more than just a curiosity. Paroxetine's antidepressant effect was tiny in those aged 25 or under on the HAMD - treatment just 9% of the placebo effect - but on the MADRS in the same age group, the benefit was 35%! So what is the HAMD measuring and why is it different to the MADRS?

Honestly, it's hard to tell because the Hamilton scale is so messy. It measures depression and the other distressing symptoms which commonly go along with it. The idea, I think, was that it was meant to be a scale of the patient's overall clinical severity - how seriously they were suffering - rather than a measure of depression per se.

Paxil: The Whole Truth?

Влияние пищевых предпочтений на частоту тревожных и депрессивных расстройств

Thus, the present study used a composite dietary quality score as well as 3 dietary patterns ("traditional," "western," and "modern") derived by factor analysis to measure overall dietary intake and controlled for age, education, socioeconomic status, physical activity, alcohol and nicotine consumption, as well as body mass index as potential confounders. The "traditional" diet was mainly comprised of vegetables, fruit, beef, lamb, fish, and whole-grain foods; the "western" diet consisted mainly of meat pies, processed meats, pizza, chips, hamburgers, white bread, sugar, flavored milk drinks, and beer; and the "modern" diet comprised fruits and salad plus fish, tofu, beans, nuts, yogurt, and red wine. Psychopathology was assessed with the Structured Clinical Interview for DSM IV-TR, Non-patient Version (SCID I/NP) and the General Health Questionnaire (GHQ-12).

The results showed that, controlled for all potential confounders, a "traditional" diet was associated with significantly lower odds of depressive and anxiety disorders, while a "western" diet was significantly associated with higher general symptoms on the GHQ-12. The "western" diet was furthermore correlated with higher odds of depressive disorders before adjustment for confounders, while adjustment reduced it to a trend. The diet quality score was inversely related with general symptoms on the GHQ-12, also when controlled for confounders. Interestingly, the authors noted a positive correlation between a "modern" diet and depressive disorders after adjustment for confounders.

The Year in Psychosis and Bipolar Disorder: Association of Diet With Depression and Anxiety

Длительность лечения тревожного расстройства

Relapse rates after 12 months of venlafaxine XR treatment were 6.7% for patients who were taking venlafaxine XR for the full 18 months, 20.0% for patients taking placebo for 12 months (months 6 to 18), and 32.3% for placebo patients who switched at month 12 to placebo (P < .14).

The study also found that patients treated with venlafaxine XR for 12 months before being shifted to placebo experienced a lower relapse rate (32.4%) than patients shifted to placebo after taking venlafaxine XR for only 6 months (53.7%; P < .03).

Chronic Anxiety Requires Long-Term Treatment to Prevent Relapse

Акампросат в лечении тревожных расстройств

BACKGROUND: Glutamate is a major excitatory neurotransmitter, while {gamma}-aminobutyric acid (GABA) is a predominant inhibitory neurotransmitter in the central nervous system. This GABA-glutamate imbalance is thought to play a role in the development of anxiety. Acamprosate calcium is thought to restore this chemical imbalance in alcohol withdrawal.

OBJECTIVE: To examine acamprosate calcium as augmentation therapy for treatment of anxiety.

METHODS: This 8-week, open-label study was designed to evaluate patients with anxiety who were stable on current medications (selective serotonin-reuptake inhibitors and serotonin-norepinephrine-reuptake inhibitors) but still symptomatic. Acamprosate was dosed at 1998 mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and the Hospital Anxiety and Depression Scale.

RESULTS: Thirteen patients enrolled in the study and received study medication. Acamprosate reduced anxiety symptoms (mean HAM-A score reduction to 8.87 from a baseline of 20). Sixty-two percent of patients receiving acamprosate achieved remission (HAM-A score ≤7). Modal dose was 1998 mg/day (range 999-1998). The most commonly reported adverse events were nausea (n = 1), gastrointestinal upset (n = 1), and increased dream activity (n = 1).

CONCLUSIONS: Acamprosate calcium may be effective augmentation therapy in patients with treatment-resistant anxiety.

Acamprosate Calcium as Augmentation Therapy for Anxiety Disorders

Статины, холестерин и аффективные расстройства

New research into cholesterol-lowering statin drugs and serotonin-1A receptors may help explain the relationships between cholesterol levels and symptoms of anxiety and depression.

Shrivastava and colleagues1 explored the effect of chronic cholesterol depletion induced by mevastatin on the function and dynamics of the human serotonin-1A receptors stably expressed in animal cells. Statins are competitive inhibitors of HMG-CoA reductase, the key rate-limiting enzyme in cholesterol biosynthesis.

Statins, Cholesterol Depletion—and Mood Disorders: What’s the Link?

Депрессия и тревожные расстройства в пожилом возрасте

Anxiety and Depression in the Elderly

Пропранолол при ПТСР

The β-blocker propranolol may interrupt reconsolidation of traumatic memories through protein synthesis inhibition, presenting a promising treatment option for posttraumatic stress disorder (PTSD), 2 new studies suggests.
Propranolol blocks β-adrenergic receptors and, if administered after subjects have actively recalled their memory, may have a 6-hour window to interrupt memory reconsolidation.

Propranolol a Promising Treatment for PTSD

Плавная vs резкая отмена антидепрессантов

Rapid discontinuation was associated with a significantly shorter time to relapse than gradual discontinuation (median, 3.6 vs. 8.4 months). The authors estimated that time to relapse after rapid discontinuation was only 25% of the average time to earlier relapses in the same patients. The findings were most evident for bipolar I and panic disorders. After rapid discontinuation, the intervals preceding relapse were similar among different drug types, but after gradual discontinuation, time to relapse was substantially longer with tricyclics than with modern antidepressants. Relapse risk was the least pronounced for medications with prolonged half-lives and was not associated with antidepressant dose, duration of illness or treatment, or concurrent treatment.

Rapid vs. Gradual Discontinuation of Antidepressants

Нелекарственные методы лечения инсомнии

Stimulus control therapy. Bootzin et al5 first evaluated stimulus control therapy for conditioned insomnia (subsequently identified as primary insomnia). This therapy’s goal is to interrupt the conditioned activation that occurs at bedtime. Patients are instructed to:

*

go to bed when sleepy
*

remain in bed for no more than 10 minutes (20 minutes if elderly) without sleeping
*

if unable to sleep, get up, do something boring, and return to bed only when sleepy
*

repeat getting up and returning as frequently as necessary until sleep onset.

For the first 2 weeks of stimulus control therapy, patients are required to self-monitor their sleep behaviors using a sleep diary. Stimulus control therapy is beneficial for primary insomnia and insomnia related to anxious preoccupation. About 70% of patients with conditioned insomnia will improve using stimulus control therapy,4 but it is not clear whether the primary effective intervention is:

*

patients dissociating conditioned responses at bedtime, or
*

the inevitable sleep restriction caused by getting out of bed.

Relaxation training. Progressive muscle relaxation is a common behavioral treatment of insomnia. Patients learn to tense and then relax individual muscles, beginning at the feet or head and working their way up or down the body. Patients are taught the difference between tension and relaxation to facilitate a relaxation response at bedtime. Another method is the body scanning technique, in which the patient “talks” to each body part, telling it to “relax… relax… relax.”

Relaxation training is predicated on the belief that insomnia is caused by somatized tension and psychophysiologic arousal. The greatest challenge to effective relaxation training is that patients need extensive daytime practice before they can bring the method to the bedroom.

Remind patients that “practice makes perfect.” Therapists often instruct patients to start practicing their relaxation method during the day while self-monitoring by sleep diary and restricting time in bed at night.2

CBTi is the most extensively investigated nonpharmacologic therapy for insomnia.6 It has been used to effectively manage comorbid insomnia in patients with psychiatric disorders,7,8 such as depression,9 generalized anxiety,10 and alcohol dependence,11 as well as those with breast cancer,12 traumatic brain injury,13 and fibromyalgia.14 Age does not appear to be a limitation; research trials show the technique is effective in elderly patients.15

CBTi incorporates cognitive strategies and behavioral interventions to improve sleep quality. Patient self-monitoring with sleep diaries and worksheets is essential.

CBTi commonly is provided in 5 to 8 sessions over 8 to 12 weeks, although studies have described abbreviated practices that used 2 sessions16 and CBTi delivered over the Internet.17 Highly trained clinical psychologists are at the forefront of therapy, but counselors and nurses in primary care settings have administered CBTi.18 For primary insomnia, CBTi is superior in efficacy to pharmacotherapy:

*

as initial treatment19
*

for long-term management4
*

in assisting discontinuation of hypnotic medication.20

Put your patients to sleep: Useful nondrug strategies for chronic insomnia

Семейная история тревожных и депрессивных расстройств и утренний уровень кортизола

Background

It is unclear whether altered hypothalamic–pituitary–adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state factor.

Aims

To examine whether HPA axis dysregulation represents a biological vulnerability for these disorders, we compared cortisol levels in unaffected people with and without a parental history of depressive or anxiety disorders. We additionally examined whether possible HPA axis dysregulations resemble those observed in participants with depression or anxiety disorders.

Method

Data were from the Netherlands Study of Depression and Anxiety. Within the participants without a lifetime diagnoses of depression or anxiety disorders, three groups were distinguished: 180 people without parental history, 114 with self-reported parental history and 74 with CIDI-diagnosed parental history. These groups were additionally compared with people with major depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary cortisol samples were obtained upon awakening, and 30, 45 and 60 min later.

Results

As compared with unaffected participants without parental history, unaffected individuals with diagnosed parental history of depression or anxiety showed a significantly higher cortisol awakening curve (effect size (d) = 0.50), which was similar to that observed in the participants with depression or anxiety disorders. Unaffected people with self-reported parental history did not differ in awakening cortisol levels from unaffected people without parental history.

Conclusions

Unaffected individuals with parental history of depression or anxiety showed a higher cortisol awakening curve, similar to that of the participants with depression or anxiety disorders. This suggests that a higher cortisol awakening curve reflects a trait marker, indicating an underlying biological vulnerability for the development of depressive and anxiety disorders.
Parental history of depression or anxiety and the cortisol awakening response

Психические расстройства при гипотиреозе и гипертиреозе

The symptoms and signs of hyperthyroidism resemble those of primary mental disorders. Overactivity of the adrenergic system caused by hyperthyroidism may explain the similarity between the clinical presentations of hyperthyroidism and mania or anxiety, as well as the precipitating role of hyperthyroidism in the development of mania or anxiety disorder. It may also explain the increased sense of well being often experienced in the early stages of hyperthyroidism.[20,21]

The relationship between hyperthyroidism and depression is less clear. Depression is usually linked to hypothyroidism, not to hyperthyroidism. However, prolonged hyperthyroidism might exhaust noradrenergic transmission and thus contribute to depression. Noradrenergic exhaustion might well occur in patients with hyperthyroidism who have bipolar disorder. In the initial phase of hyperthyroidism, thyroid hormone stimulation of the noradrenergic system may cause mania; later, when noradrenergic neurotransmission is exhausted, it may contribute to depression.[21]

Mental symptoms and disorders secondary to hyperthyroidism should be treated first by restoring euthyroidism. Most mental symptoms, including depression, usually resolve once euthyroidism has been regained. Treatment with beta-adrenergic antagonists alone may quickly relieve many symptoms, including mental symptoms, even if euthyroidism is not restored,[22] providing evidence that overactivity of the adrenergic system is largely responsible for mental symptoms in hyperthyroidism.

Thyroid deficits are frequently observed in bipolar patients, especially in women with the rapid cycling form of the disease.[24] Both subclinical hypothyroidism and subclinical hyperthyroidism increase the risk for Alzheimer's disease, especially in women.[25] However, most hypothyroid patients do not meet the criteria for a mental disorder.

A recent study evaluated brain glucose metabolism during T4 treatment of hypothyroidism. A reduction in depression and cognitive symptoms was associated with restoration of metabolic activity in brain areas that are integral to the regulation of mood and cognition.[26••]

In hypothyroidism, replacement therapy with T4 remains the treatment of choice and resolves most physical and psychological signs and symptoms in most patients. However, some patients do not feel entirely well despite doses of T4 that are usually adequate.[27] In T4-treated patients, it was found that reduced psychological well being is associated with occurrence of polymorphism in the D2 gene,[28••] as well as in the OATP1c1 gene.[29]

Thyroid hormone replacement with a combination of T4 and T3, in comparison with T4 monotherapy, improves mental functioning in some but not all hypothyroid patients,[30,31•] and most of the patients subjectively prefer combined treatment.[32] Two studies have evaluated whether D2 polymorphism is associated with changes in psychological well being after combined T4 and T3 treatment. One underpowered study[33] reported a trend toward improvement. In a second study[28••] involving a very large sample, D2 polymorphism was associated with improvement in psychological well being after T4 and T3 treatment.

Thyroid Disease and Mental Disorders: Cause and Effect or Only comorbidity?

Фармакотерапия социофобии

Pharmacotherapy for Social Anxiety Disorder: An Update

Анксиолитический эффект сока черноплодной рябины у крыс

"The main biologically active constituents of Aronia melanocarpa fruit juice (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on anxiety using the social interaction test, on locomotor activity in the open field test and on working memory in the object recognition test in rats. AMFJ showed an anxiolytic-like effect which was demonstrated by a dose-dependent increase in the time of active social contacts between the test partners. The effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg). AMFJ neither changed significantly horizontal and vertical locomotor activity, nor did it adversely affect working memory. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved."

Anxiolytic-like effect of Aronia melanocarpa fruit juice in rats.