Does sickle cell disease have a psychosomatic component? A particular focus on anxiety and depression.

Sickle cell disease, an early-age genetic condition, encompasses a range of blood disorders with severe complications. This disease is characterized by the synthesis of abnormal hemoglobin molecules, which tend to polymerize due to their low solubility upon deoxygenation in the peripheral capillary beds, resulting in sickle-like red blood cells. Sickled cells lose their normal functioning and hemodynamic properties, leading to chronic fatigue as well as to episodes of painful crises. Over the last two decades, a growing body of clinical evidence has pointed out that these somatic complaints can give rise to neuropsychiatric disorders, among which anxiety and depression are the most common, that worsen the health-related quality of life in patients. At first glance, this somatic influence may be unsurprising, as both anxiety and depressive signs are prevalent in almost all chronic diseases. However, in the case of a genetic condition such as sickle cell disease whose somatic disturbances are predetermined, the fact that mood disorders can increase fatigue and pain through a psychosomatic component has attracted increasing attention. In this review, we address the hypothesis of a psychosomatic component in patients with sickle cell disease by underlining the most relevant clinical studies that have highlighted the existence of a bidirectional link between physical and psychological sequelae, which are reported to be relieved not only by pharmacological cotreatments but also by the concomitant application of cognitive behavioral therapy.

Effects of hesperidin on formaldehyde-induced toxicity in pregnant rats.

This experimental study aimed to investigate the protective effect of a bioflavonoid, hesperidin (HP), on formaldehyde (FA)-related pathophysiological and behavioral outcomes in pregnant rats and developmental aspects in their offspring. Female Wistar rats were subjected to perigestational exposure to FA (2 mg/kg/day per os) with a concomitant treatment with HP (50 mg/kg/day per os). Pregnant rats were weighed throughout gestation and tested in two behavioral paradigms (elevated plus-maze and open field) at gestational days (GD) 1, 10 and 19 to evaluate the anxiety-like behavior and locomotive alterations. Another subset of rats was decapitated at GD19 to determine the hematological profile along with cortisol, 17ß-estradiol, and progesterone plasma levels. Reproductive and fetal measures and observations were also performed to check for developmental deformities. Significant body weight loss, hemato-immune decline, hormonal changes, anxiety and lethargy signs, locomotor disabilities, reproductive failure and fetal weight decrease were observed in FA-exposed rats. Treatment with HP alleviated the reproductive and fetal weight defects. Its behavioral benefits were only seen at GD1 and 10. This flavanone ameliorated some hematological parameters, decreased cortisol levels and increased 17ß-estradiol rates. A potential preventive impact of HP was found against FA toxicity in pregnant rats.

Effects of quercetin on predator stress-related hematological and behavioral alterations in pregnant rats and their offspring.

This study aims at investigating the effect of a psychogenic stress during gestation on the behaviour and haematological indices in dams as well as on the neonatal haematological status and periadolescent behaviour in their offspring. Moreover, the ability of quercetin, a natural flavonoid, to prevent the stress-induced changes was estimated. Pregnant Wistar rats were pretreated with quercetin before the exposure to a predator stress on gestational day 19. Post-stress maternal anxiety-like behaviour was assessed with a concomitant haematological analysis. In the offspring, haematological analysis and behavioural testing were performed during the postnatal stage. Our results revealed that predator stress causes an anxiety-like behaviour in dams along with a decrease in erythrocytes, a microcytosis, and a thrombocytosis. Prenatally stressed neonates manifested microcytosis and thrombocytosis with a significant polycythemia. Signs of motor hyperactivity, anxiety-like behaviour, and memory dysfunction were detected at periadolescence. Quercetin pretreatment alleviated the stress-induced behavioural and haematological impairments in dams but failed to attenuate the haematological changes in neonates. A sex-dependent effect of quercetin on behaviour was found at periadolescence. Our findings suggest that, besides a beneficial effect on haematological and behavioural anomalies in traumatized dams, quercetin may lastingly modulate the behaviour of their progeny.

Quercetin mitigates Adriamycin-induced anxiety- and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats.

This study was designed to evaluate the effect of quercetin, a natural flavonoid, on behavioral alterations, brain oxidative stress, and immune dysregulation caused by a chemotherapeutic agent, Adriamycin (ADR; 7 mg/kg of body weight). Different subsets of male Wistar rats were used to determine the benefit of quercetin on ADR-related depression-like and anxiety-like behaviors in the forced swim test, open field, and elevated plus maze, respectively. Quercetin (60 mg/kg of body weight) was administered 24, 5, and 1 h before the test session of forced swim test (FST) or at the same time points before the elevated plus maze/open field (EPM/OF) tests. Other subsets of rats were sacrificed after quercetin injections to assess the plasma corticosterone level, the brain oxidative status, and the immune cell count. Our results indicate that quercetin alleviated the anxio-depressive-like behavior, attenuated the brain oxidative stress, and suppressed the corticosterone excess that appeared following ADR treatment. The ADR-induced immune disturbance was slightly diminished after quercetin administration, especially for the lymphocyte count. This study suggests that quercetin can mitigate the neurobehavioral and immunological impairments that manifest in ADR-treated rats. Therefore, the combination of quercetin treatment with the chemotherapeutic regimen seems to be beneficial against chemotherapy-related complications.

Quercetin alleviates predator stress-induced anxiety-like and brain oxidative signs in pregnant rats and immune count disturbance in their offspring.

This study was performed in rats to investigate the effect of a psychogenic stress during late gestation on the immediate behavior and brain oxidative status in dams as well as on the immune cell counts in their offspring up to weaning. Besides, the ability of quercetin (a natural flavonoid) to prevent stress effects was evaluated. Quercetin was orally administered for 6 consecutive days before the pregnant rats were acutely exposed to predator stress on gestational day 19. Post-stress corticosterone level, brain oxidative stress parameters and anxiety-like behavior were assessed in dams, whereas immune cell counts were postnatally determined in both male and female pups. Predator stress caused an oxidative stress in the brain and elicited an elevation in plasma corticosterone with concomitant behavioral impairment in dams. Prenatally-stressed pups mainly showed a decrease in total leukocytes and lymphocytes along with monocytosis and granulocytosis, but these changes were sex-dependent throughout the postnatal period studied. Quercetin pretreatment blocked the stress-induced corticosterone release and alleviated the brain oxidative stress with the maternal anxiety measures being slightly attenuated, whereas its effects on the offspring immune cell counts were mostly revealed at birth. Our findings suggest that late gestational exposure to traumatic events may cause anxiety symptoms in dams, in which corticosterone and brain oxidative stress play a certain role, and trigger negative immune changes in the early postnatal life of progeny. Notably, quercetin intake before such adverse events seems to be beneficial against negative outcomes in both dams and offspring.

Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats.

Chemotherapeutic regimens have been indicated to negatively impact the quality of life for patients. Adriamycin (ADR) is an effective chemotherapeutic agent widely employed for the treatment of human's malignancies; however, it may cause serious side effects. The present study was aimed at investigating the effects of acute administration of ADR on cognitive alterations, brain oxidative status and immune dysregulation in male Wistar rats. Treated animals received a single intraperitoneal injection of ADR (7 mg/kg). Control ones received physiological saline only. Behavioral effects were tested in the elevated plus-maze and the open field which showed that drug-treated rats displayed anxious behavior and deteriorations in the locomotive and exploratory activities over the 72 h following ADR injection as compared to controls. Assessment of brain antioxidant capacity in ADR-injected animals revealed an increase in glutathione-S-transferase activities and malondialdehyde levels while a decrease in glutathione concentrations when compared with the vehicle-treated group. Our results indicated that ADR administration decreased total leukocyte, lymphocyte and granulocyte counts, while enhanced monocyte levels. Moreover, white blood cells (WBC) relative counts in ADR-treated rats showed a significant increase in monocytes and granulocytes and a decrease in lymphocytes as compared to controls. This study suggests that ADR-related cognitive impairments are associated with brain oxidative stress and myelosuppression.