The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature.

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

The role of cholesterol levels in mood disorders and suicide.

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

Ultradian variation of nerve growth factor plasma levels in healthy and schizophrenic subjects.

Some studies in animal models showed that several neurotrophins may be implicated in the regulation of light-dependent suprachiasmatic pacemaker and in other functions implicated in long-term memory acquisition during sleep. However, no data are known about the role played by NGF in ultradian regulation in humans. The aim of this study was to investigate whether or not there is a natural diurnal fluctuation during daytime in healthy and schizophrenic subjects with a normal light/dark cycle. In a sample of 33 subjects (10 male schizophrenics and 23 healthy subjects) an ELISA assay was used to study the ultradian NGF cycle in blood samples at 9.00, 13.00 and 20.00 hours. The study showed an ultradian rhythm of NGF in healthy subjects with a "V" trend: higher at 9:00 and 20:00 and lower at 13:00. We also show significant differences between male and female controls. No NGF ultradian rhythm among schizophrenic patients compared to healthy subjects was found. The results of this study lead to a rhythmic NGF regulation that appears altered in schizophrenics, where higher levels in the morning and lower levels in the evening were observed, compared to the controls, and support the hypothesis of a role played by NGF in schizophrenia.

Flunitrazepam a benzodiazepine most used among drug abusers.

Flunitrazepam (FZ) is a sedative/hypnotic nitro-benzodiazepine. This drug has been accepted by both patients and physicians and in the last 20 years flunitrazepam has been included and studied in many clinical trials so, in many countries, flunitrazepam is one of the most prescribed hypnotic. Since 1980 it has been found that FZ began to be a popular drug among drug abusers all over the word. However, little is known about the difference between Fz and other Benzodiazepines in capacity to produce physiologic dependence or in ability to produce drug taking or drug seeking behaviour. Flunitrazepam has little risk of abuse by the vast majority of patients; however when the drug is taken i. v. or intranasally, its effect is much faster and risk of abuse is much greater. In this report we examine the reasons why some populations of drug abusers prefer flunitrazepam over the other benzodiazepines.