Keywords: Anxious Depression; Monoamine Oxidase; Semi carbazide-Sensitive Amine Oxidase; Middle-Mass Endotoxic Molecules
Data from the World Health Organization indicate that depression and anxiety are the most common concomitant disorders in the primary healthcare system . These two states significantly overlap in terms of clinical symptoms and various pathophysiological mechanisms of depression and anxiety can be detected in 42-100% of patients with depression . Many aspects of pathogenetic and pathophysiological mechanisms of depressions need further investigations. It is especially important regarding biochemical investigations. The aim of the study was to investigate the state of aminergic metabolism and some parameters reflecting the disturbances of homeostasis in patients with anxious depression.
Material and Methods
There were investigated 21 patients with anxious depression.
The patient’s state according to ICD-10 criteria [according to
International Classifications of Diseases, tenth edition, clinical
modification (ICD-10-CM)]  was defined as a depressive episode
as an independent disease (F32.1) and together with recurrent
depressive disease (F33.1). The presence of anxiety together with
depression was the main indication for the inclusion into the
investigation. The clinical severity of the illness was assessed using
the Hamilton Rating Scale for depression (HAM-D) (21 items) and
the Hamilton Rating Scale for anxiety (HAM-A) .
Control group consists of 15 healthy volunteers. Investigation was performed in accordance with the permission of the local ethical committee of Moscow Research Institute of Psychiatry (N 16, 13.03.2017). Biochemical parameters were estimated at the admission. The activities of platelet monoamine oxidase (MAO) and serum semi carbazide-sensitive amine oxidase (SSАО) were estimated by methods of  and , respectively. Concentration of middle-mass endotoxic molecules (MMEM) in blood plasma was estimated by method of . The significance of the differences was assessed using the Wilcoxon test Data for patients with depression were presented as the mean ± the error of the mean. Statistical significance was implied by p<0.05.
Results and Discussion
Data from the Hamilton scale (HAM-D) showed that at admission the total score was 21.83, which is consistent with severe depressive disorder. HAM-A data gave a total score of 18.4 which is also consistent with severe anxiety. At admission, all patients were characterized by the significant increase in platelet MAO activity (by 95%), decrease of serum SSАО activity (by 43%) and increase of MMEM concentration (by 86%) in comparison with control values (Table 1). This implies that anxious depression is characterized by the strongly pronounced disturbances of aminergic metabolism and homeostasis.
*p<0.05 **p<0.001 – in comparison with controls; MAO - monoamine oxidase; SSAO - semi carbazide-sensitive amine oxidase; MMEM - middle-mass endotoxic molecules
The disturbance of MAO activity in anxiously depressed patients
may be indicative of damage of membrane structures (this enzyme
is an integral component of the external mitochondrial membrane),
resulting in the appearance in the blood of different toxic end
products (aldehyde and ammonia). Changes in MAO activity can
disturb the equilibrium between serotonin and epinephrine that
play important role in the pathophysiology of the condition .
Hydrogen peroxide formed in the reaction of deamination catalyzed
by MAO represents the main source of free radicals in the brain .
Thus, the elevation of MAO activity in these patients can induce the
activation of free radical processes and lipid peroxidation that leads
to the activation of oxidative stress. From the other side activation
of oxidative stress is followed by the disturbances of mitochondria
and the damage of blood-brain barrier. This statement is supported
by data that depression is followed by damage of blood-brain
barrier structures . Taken together, these results suggest that
an increased MAO activity precipitates a cascade of negative
Serum SSAO is an enzyme that is involved in the oxidation both xenobiotics and endogenous amino-containing metabolites . The precise physiological and pathophysiological role of this enzyme is not known. SSAO can convert some endogenous amines, such as methylamine and aminoacetone, into highly toxic compounds - formaldehyde, methylglyoxal and acrolein . Therefore, it is possible that an increase in the blood concentrations of these substances following stressful life events, as a depression, can exert harmful influences. It is supposed that increase of toxic metabolite concentrations in depressed patients promotes the intensification of endogenous intoxication. In previous studies, we proposed that the degree of endogenous intoxication can serve as a parameter of intensity of the disturbances of homoeostasis [6, 10].
Endogenous intoxication (endotoxicosis) is a pathophysiological process that is characterized by the formation and accumulation in tissues and body fluids of different substances and metabolites (endotoxins), in excessive concentrations or in forms that are not characteristic for the normal metabolism [6,10]. Increased level of MMEM, activation of free radical processes and lipid peroxidation, reactions catalyzed by MAOs and SSAO and so on make a major contribution to the development of endotoxicosis . In patients with anxious depression MMEM concentration was elevated more than twofold support this thesis. It is postulated that, during the development of the mental disorders, there is an activation of catabolic processes that increase the concentration of different MMEM components. The increase of the MMEM concentration in blood plasma is indicative of the aggravation of the degree of endogenous intoxication as well as patient’s clinical status.
These findings point out that anxious depression is followed by the profound biochemical and metabolic disturbances. We suppose that investigated parameters can serve as biomarkers of the severity of the condition.
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