No abstract

Essential elements are very important for the proper functioning of the human body. They are required for fundamental life processes such as cell division and differentiation and protein synthesis. Thus a deficiency of these essential elements is associated with an enormous health risk that can ultimately lead to death. In recent years, studies have provided valuable information on the involvement of essential elements in psychiatric disorders, in particular depression and anxiety. There is strong evidence indicating that deficiency of essential elements can lead to the development of depressive and/or anxiogenic behaviour and supplementation can enhance therapeutic effect of antidepressants and anxiolytics. This review presents the most important results from preclinical and clinical studies showing involvement of essential elements such as zinc, magnesium, lithium, iron, calcium and chromium in depression and anxiety. From these studies it is evident that different types of depression and anxiety respond to treatment at different receptors indicating that the underlying mechanisms are slightly different. Furthermore, administration of low dose antidepressants supplemented with an element is effective and can reduce unwanted side effects in different types of depression/anxiety.

The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2-methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6-methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydrochloride (HBK-15) in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM) in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic α1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14—FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg) and (HBK-15—FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg). We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg) and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg) possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds.

Depression is a serious global illness, becoming more and more common in developed countries. Because of specific symptoms it is considered as a leading cause of disability all over the world with a high death factor due to suicides. There are many antidepressants used in the therapy, but still more than 30% of patients do not respond to the treatment. The heterogeneous nature of the illness and its complex, unclear aetiology may be responsible for these difficulties. Next to the main monoaminergic hypothesis of depression there are also many other approaches connected with the pathophysiology of the disease, including hypothalamic-pituitary-adrenal axis dysregulation, dopaminergic, cholinergic, glutamatergic or GABA-ergic neurotransmission. Nevertheless, it can be unambiguously stated that serotonergic, noradrenergic and dopaminergic systems are precisely connected with pathogenesis of depression, and should be therefore considered as valuable targets in patients' treatment. Bearing that in mind, this review presents the role of serotonergic, adrenergic and dopaminergic receptors in antidepressant-like effect.

In this paper we continue to discuss the involvement of essential elements in depression and anxiety, and the possible mechanisms that link elements to the neurobiology underlying depression/anxiety. The present paper is focused on copper, selenium, manganese, iodine and vanadium. Different aspects of relationship between elements and depression or anxiety are reviewed, e.g. the association of the amount of an element in a diet or the serum level of an element and depressive or anxiety-like symptoms. Moreover, the relation of selected elements to the pathophysiology of depression or anxiety is discussed in the context of enzymes which require these elements as co-factors and are involved in the underlying pathophysiology of these disorders.