Neuropsychological functioning in young subjects with generalized anxiety disorder with and without pharmacotherapy.

The purpose of this study was to investigate the neuropsychological functioning and the effect of antidepressant drug intake on cognitive performance in a group of relatively young generalized anxiety disorder (GAD) patients. Forty patients with a DSM-IV diagnosis of GAD and 31 healthy subjects participated in the study (Control group, CON). None of the selected subjects had comorbid depression. GAD subjects were divided into two different subgroups: 18 were taking antidepressants [GAD-pharmacotherapy (GAD-p group)] and 22 were treatment-naïve (GAD group). Each group was administered with a comprehensive neuropsychological battery to assess attention, memory and executive functions. Performance on executive and non-verbal memory tasks of both GAD groups was largely worse than the CON group. However, these deficits seem to be more marked in patients taking antidepressants, especially in the domains of attention, non-verbal memory and executive functions. The present study indicates that GAD is associated with cognitive impairments among young adults. However, the observed association of neuropsychological deficits and the use of pharmacotherapy suggest a possible effect of antidepressant treatment on attention, executive functioning and non-verbal memory.

The emerging role of melatonin agonists in the treatment of major depression: focus on agomelatine.

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual subtreshold symptoms. This compound showed a relative early onset of action as well as an excellent safety and tolerability profile linked to a low discontinuation rate in MDD patients. Moreover, some data suggest that agomelatine has not only antidepressant effects but also anxiolytic effects, with a potential benefit both on anxiety symptoms associated with MDD and in the treatment of generalised anxiety disorder. This review will summarise the role of the melatonergic system in MDD and will describe the characteristics of agomelatine, focusing on its efficacy and safety in the treatment of MDD.

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.

Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder.

The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.

The role of C-reactive protein in mood disorders.

Recently, a possible relationship between C-Reactive Protein (CRP), a marker of underlying low-grade inflammation, and mood disorders has been proposed by some researchers. The aim of this review is to elucidate the current facts and views about CRP in mood disorders such as Depressive and Bipolar Disorders. Several studies have examined the relationship between affective disorders and CRP, but the majority of the studies in literature have been limited by retrospective, case-controlled study design, and very few studies have examined the relationship between depression and CRP in large study samples. In conclusion, the role of CRP in mood disorders is, to date, intriguing but somewhat unclear. Further prospective studies are needed to introduce the CRP in clinical settings as a marker of affective states and suicidability.