Lucio Tonello

The use of artificial neural networks to study fatty acids in neuropsychiatric disorders

BackgroundThe range of the fatty acids has been largely investigated in the plasma and erythrocytes of patients suffering from neuropsychiatric disorders. In this paper we investigate, for the first time, whether the study of the platelet fatty acids from such patients may be facilitated by means of artificial neural networks.MethodsVenous blood samples were taken from 84 patients with a DSM-IV-TR diagnosis of major depressive disorder and from 60 normal control subjects without a history of clinical depression. Platelet levels of the following 11 fatty acids were analyzed using one-way analysis of variance: C14:0, C16:0, C16:1, C18:0, C18:1 n-9, C18:1 n-7, C18:2 n-6, C18:3 n-3, C20:3 n-3, C20:4 n-6 and C22:6 n-3. The results were then entered into a wide variety of different artificial neural networks.ResultsAll the artificial neural networks tested gave essentially the same result. However, one type of artificial neural network, the self-organizing map, gave superior information by allowing the results to be described in a two-dimensional plane with potentially informative border areas. A series of repeated and independent self-organizing map simulations, with the input parameters being changed each time, led to the finding that the best discriminant map was that obtained by inclusion of just three fatty acids.ConclusionOur results confirm that artificial neural networks may be used to analyze platelet fatty acids in neuropsychiatric disorder. Furthermore, they show that the self-organizing map, an unsupervised competitive-learning network algorithm which forms a nonlinear projection of a high-dimensional data manifold on a regular, low-dimensional grid, is an optimal type of artificial neural network to use for this task.

Bio Molecular Considerations in Major Depression and Ischemic Cardiovascular Disease

In our study we have evaluated the theme of the platelet fatty acid composition in subjects with a clinical diagnosis of Major Depression (MD), in subjects with a clinical diagnosis of Ischemic Heart Disease (IHD) according to the coronary angiography and in control subjects. We have analyzed all the groups without taking in account therapies, gender and age. As far as we know, the platelet fatty acid composition has never been analyzed before, in MD. The results obtained with the Self Organizing Map (SOM) show the evidence of three fatty acids, Arachidonic Acid (AA), Linoleic Acid (LA), and Palmitic Acid (PA) in a peculiar position with respect to the biochemical characterization of MD and three fatty acids, Arachidonic Acid (AA), Linoleic Acid (LA) and Oleic Acid (OA) in a peculiar position with respect to the biochemical characterization of the IHD. Bio molecular considerations are made about the possibility of controlling positive changes in platelet viscosity, in both pathologies.

A comparison of oxidative stress in smokers and non-smokers: an in vivo human quantitative study of n-3 lipid peroxidation

BackgroundCigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath.MethodsSamples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry.ResultsThe two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75).ConclusionOur results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

Human depression: A new approach in quantitative psychiatry

The biomolecular approach to major depression disorder is explained by the different steps that involve cell membrane viscosity, Gsα protein and tubulin. For the first time it is hypothesised that a biomolecular pathway exists, moving from cell membrane viscosity through Gsα protein and Tubulin, which can condition the conscious state and is measurable by electroencephalogram study of the brains γ wave synchrony.

Fatty acids, membrane viscosity, serotonin and ischemic heart disease

Novel markers for ischemic heart disease are under investigation by the scientific community at international level.This work focuses on a specific platelet membrane fatty acid condition of viscosity which is linked to molecular aspects such as serotonin and G proteins, factors involved in vascular biology.A suggestive hypothesis is considered about the possibility to use platelet membrane viscosity, in relation to serotonin or, indirectly, the fatty acid profile, as indicator of ischemic risk.

Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology

Due to the relationship between biology and culture, we believe that depression, understood as a cultural and existential phenomenon, has clear markers in molecular biology. We begin from an existential analysis of depression constituting the human condition and then shift to analysis of biological data confirming, according to our judgment, its original (ontological) structure. In this way philosophy is involved at the anthropological level, in as much as it detects the underlying meanings of depression in the original biological-cultural horizon of human life. Considering the integration of knowledge it is the task of molecular biology to identify the aforementioned markers, to which the existential aspects of depression are linked to. In particular, recent works show the existence of a link between serotonin and osteoporosis as a result of a modified expression of the low-density lipoprotein receptor-related protein 5 gene. Moreover, it is believed that the hereditary or acquired involvement of tryptophan hydroxylase 2 (Tph2) or 5-hydroxytryptamine transporter (5-HTT) is responsible for the reduced concentration of serotonin in the central nervous system, causing depression and affective disorders. This work studies the depression-osteoporosis relationship, with the aim of focusing on depressive disorders that concern the quantitative dynamic of platelet membrane viscosity and interactome cytoskeleton modifications (in particular Tubulin and Gsα protein) as a possible condition of the involvement of the serotonin axis (gut, brain and platelet), not only in depression but also in connection with osteoporosis.

Running the hypothesis of a bio molecular approach to psychiatric disorder characterization and fatty acids therapeutical choices

Beyond the conviction that Major Depression can found its origin in genetics [1-3] a bio molecular mechanism could be hypothesized from what emerged from the studies on platelets fatty acid composition in human (normal and depressive subjects) which allowed classifying the depressive disorder [4] using an Artificial Neural Network (Self Organizing Map-SOM) [5], as mathematical tool, because of the complexity of the membrane dynamics. Rapid changes in membrane lipid composition or in the cytoskeleton could modify neuronal signalling. In the knowledge to have found something that could have implications in the understanding of some aspects of psychiatric disorders and a very suggestive hypothesis was build as summarized in Figure ​Figure1.1. In figure ​figure11 is described the molecular depression hypothesis made according to Cocchi and collegues [4], Donati and collegues [6], Hameroff and Penrose [7]. The membrane viscosity can modify the Gsα protein status. The Gsα protein is connected with Tubulin. Tubulin, depending on local membrane lipid fase concentration, may serve as a positive or negative regulator of phosphatidylinositol bisphosphate (PIP2) hydrolysis, such as Gsα protein does. Tubulin is known to form high-affinity complexes with certain G proteins. The formation of such complexes allows tubulin to activate Gsα, which, in turn, can activate the Protein Kinase C and fosters a system whereby elements of the cytoskeleton can influence G-protein signalling. Rapid changes in membrane lipid composition or in the cytoskeleton might modify neuronal signalling. We have hypothesized that through this mechanism is possible to modify the consciousness state and that it is mesurable through gamma syncrony EEG. Figure 1 The molecular depression hypothesis. There are strong reasons to think that each fatty acid combination of Palmitic Acid (PA), Linoleic Acid (LA) and Arachidonic Acid (AA), in platelet, is responsible of the membrane viscosity and, therefore, of the molecular conditioning of the cellular stuctures (Gsα and Tubulin) and that the main therapeutic target is the reduction of the Arachidonic Acid.

Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking broken symmetries in molecular biology, mood disorders and personalistic emergentism

In this paper we present a mechanistic model that integrates subneuronal structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain. We also argue that subtle changes in the composition of the membrane’s fatty acids may lead to down-stream effects causing dysregulation of the membrane, cytoskeleton and their interface. Such exquisite sensitivity to minor changes is known to occur in physical systems undergoing phase transitions, the simplest and most studied of them is the so-called Ising model, which exhibits a phase transition at a finite temperature between an ordered and disordered state in 2- or 3-dimensional space. We propose this model in the context of neuronal dynamics and further hypothesize that it may involve quantum degrees of freedom dependent upon variation in membrane domains associated with ion channels or microtubules. Finally, we provide a link between these physical characteristics of the dynamical mechanism to psychiatric disorders such as major depression and antidepressant action.

Human and Animal Brain Phospholipids Fatty Acids, Evolution and MoodDisorders

The purpose of this paper is to connect the experimental evidence concerning brain phospholipids fatty acids composition by comparing the first warm-blooded animal in the phylogeny (birds) with the human brain at various ages of life (from the fetal period until the eightieth year of age). The particularity of our investigation is an almost unique opportunity for groped a hypothesis about the evolutionary aspects of the behavior of brain and consciousness, as represented in the human and animal world, as a result of the evidence that led to the diagnostic classification of mood disorders in humans, in their similarity with some animal species. A logical sequence of considerations about the mood disorder diagnosis, due to unequivocal evidence by the use of mathematical tools that cannot be manipulated, it leads to results that most probably indicate and suggest the existence of a common brain “biochemical house“, in man and animal. This “common house” will become more and more complex, during evolution, from animal to man, respecting the concept of the molecular equilibrium and allowing to each living being the adaptation to their needs and their roles. Small deviations from the biochemical equilibrium of brain fatty acids can manifest pathological behavioral responses, much amplified. Everything seems to be witnessed by the strong classificatory correspondence of the platelets fatty acids which correspond to psycho pathologies, especially for the Linoleic acid and alpha Linolenic acid, in particular the Linoleic Acid, which, to varying percentages, it may correspond to psychopathological phenomena.

Molecular Contiguity between Human and Animal Consciousness throughEvolution: Some Considerations

This work suggests the possibility of the existence of contiguity in the molecular evolution of consciousness, between man and animal. From the experimental point of view and in terms of hypotheses, it seems that many elements lead to considerations about a common molecular evolutionary origin of the consciousness in animals and humans. It seems, also, evident that the increasing levels of complexity of consciousness can correspond to the evolutionary process. The work discusses a scientific speculation about the possible role of serotonin and thermoregulation in the evolution of consciousness of living beings.