Alprazolam (a benzodiazepine in the group of the triazolo-benzodiazepines) is a potent drug for the treatment of panic disorder. This is possible due to four different interactions with neurotransmitter systems. First, it facilitates, as all diazepines, the inhibitory acitivity of gamma-amino-butyricacid (GABA). The chemical structure differs from the benzodiazepines by incorporation of the triazoloring. Due to this triazoloring, the drug has three additional modes of action. These modes of action inhibit the locus coeruleus which plays a role in the origin of panic disorder. A first specific action is a stimulation of the serotonergic system. Triazolobenzodiazepines are also α2-adrenoreceptor agonists. Both mechanisms are responsible for inhibition of the locus coeruleus. Triazolo-benzodiazepines inhibit the platelet-activating-factor (PAF). PAF stimulates the corticotropin-releasing-hormone (CRH). This hormone stimulates the locus coeruleus. CRH in patients with panic attacks is elevated. This could be a result of hyperactive metabolism of the right parahippocampal area, which is observed in patients with panic attacks. Triazolo-benzodiazepines decrease the activity of the locus coeruleus because of a low CRH-level due to inhibited PAF.

Reported (ir)reversibility of neurological and psychiatric symptoms induced by Phenytoin intoxication is being discussed by means of a case report concerning a 40-year old man who sets fire to his house during a psychosis. Observation after admission to a general psychiatric hospital, following a short period of detention, leads to diagnosing neurological and psychiatric symptoms due to chronic Phenytoin intoxication. Discontinuation of Phenytoin supply induces partial remission of the symptoms. Literature on the subject is being revised.

Zinc is a trace element which plays a fundamental role in a wide range of biochemical processes in living organisms. Zinc is an essential component of various proteins and is an important factor for physiological function of the mammalian nervous and immune systems. In the central nervous system (CNS), zinc is found at high concentrations in hippocampal neurons. These neurons possess mechanisms for zinc uptake and storage in synaptic terminals and for the stimulation of zinc release along with neurotransmitters. In the central nervous system, zinc modulates predominantly the excitatory (glutamatergic) and inhibitory (GABAergic) amino acid neurotransmission pathways. In the immune system, zinc is necessary for the physiological activity of the thymus and T-cell-dependent responses. Zinc deficiency impairs the activities of the neuroendocrine and immune systems in mammalian organisms. This paper reviews the alterations in the blood and brain zinc concentrations in relation to the neuroimmune pathophysiology and treatment of depression. Major depression is related to lowered serum zinc concentrations, which may be caused by the acute phase and the inflammatory response in that illness. Repeated administration of antidepressants selectively increases and redistributes brain zinc in the hippocampus. Since zinc is an inhibitor of the glutama-te/NMDA receptor, these data are in accordance with the glutamate hypothesis of antidepressant action.

This article describes a number of studies by our research group to find brain structures that may be involved in the symptoms of idiopathic depression, depression in Alzheimer's disease and depression in Parkinson's disease. Until recently, idiopathic depression has generally been related to deficiencies of aminergic systems. In Alzheimer patients we found a strong decrease in the number of neurons in the locus coeruleus and brain noradrenaline concentrations, but in depressed Alzheimer patients we did not find an extra de crease. This is in agreement with the finding that there is no cell loss in the locus coeruleus in idiopathic depression. We did find, however, that the number of corticotropin-releasing hormone-, vasopressin- and oxytocin expressing neurons, the number of corticotropin-releasing hormone neurons co-expressing vasopressin and the amount of corticotropin-releasing hormone -mRNA in idiopathic depression were strongly increased in the paraventricular nucleus of the hypothalamus. This result supports the hypothesis on the pathogenetic involvement of the hypothalamo-pituitary-adrenal axis in depression and is of clinical relevance, since it may provide a theoretical rationale for antidepressive therapy with CRH antagonists.