OJD  Vol.3 No.2 , May 2014
Platelet’s Fatty Acids and Differential Diagnosis of Major Depression and Bipolar Disorder through the Use of an Unsupervised Competitive-Learning Network Algorithm (SOM)
Abstract: Aim of the study: The main purpose of this work was to verify, through the study of three fatty acids of platelets (namely: Palmitic Acid—PA, Linoleic Acid—LA, Arachidonic Acid—AA) the ability to distinguish adult subjects with Major Depression (MD) from those with Bipolar Disorder (BD), using an artificial neural network (Self Organizing Map—SOM) and an indirect index of the viscosity of the membrane (B2), in agreement with previous results; secondly, the ability to understand any similarities between children and adults in the molecular characterization of mood disorders, both in general and in relation to a subset of individuals with suicidal ideation, indicated by the survey instruments used (SOM). Design: The study design, in order to achieve the objectives, has forecast the recruitment of three groups of subjects without regard to sex, age, food intake patterns, or pharmacological therapies: 1) Controls; 2) Subjects with Major Depression; 3) Subjects with Bipolar Disorder. They were provided for the following investigations: 1) Platelet Fatty Acids analysis; 2) Plasma and platelet serotonin levels; 3) Oxidative stress and inflammation markers. Moreover, the data of the fatty acids of platelets, previously obtained by a group of children were used, for comparison, in the SOM, with adults surveyed. Subjects participating in the study: All participants, volunteer, were recruited in the judgment of psychiatrists as they presented themselves to the office visit of the “Dipartimento di Salute Mentale”, ASUR 4, Fano, Italy. All subjects were submitted to a semi-structured interview based on DSM-IV-TR criteria. 21-item Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impressions Scale (CGI), Symptom Checklist-90 (SCL-90), and Hypomania/Mania Symptom Checklist (HCL-32) were also applied to each patient. Adult subjects who did not give consent, patients with a diagnosis other than an affective disorder and subjects in their first clinical episode were excluded. The study was double blind. Outcomes: The results obtained have confirmed the main objective of the study. It was possible to obtain, in fact, the recognition of individuals with Major Depression and Bipolar Disorder, using the SOM and the index B2. Value of the study: The methodology used in this study may be of utility, such as quantitative diagnostic support to the psychiatrist, in order to reduce the high error that occurs in the first diagnosis, with regard to mood disorders. Limitations of this study: The limitations of this study are mainly related to the number of controls. They should have been more numerous such as the number of suicidal ideations. About the comparison with children, the main limitation seems to be the lack of psychiatric diagnosis of children, so that any results just assume the value of hypotheses. Future Research: Because of the strong classificatory properties of the SOM, it would require a RCT in a larger sample of subjects with mood disorders with the aim of assessing whether it is possible to identify subgroups of subjects with respect to the classical psychiatric classification and corresponding to different therapies. The same is for suicidal ideation.
Cite this paper: Benedetti, S. , Bucciarelli, S. , Canestrari, F. , Catalani, S. , Mandolini, S. , Marconi, V. , Mastrogiacomo, A. , Silvestri, R. , Tagliamonte, M. , Venanzini, R. , Caramia, G. , Gabrielli, F. , Tonello, L. and Cocchi, M. (2014) Platelet’s Fatty Acids and Differential Diagnosis of Major Depression and Bipolar Disorder through the Use of an Unsupervised Competitive-Learning Network Algorithm (SOM). Open Journal of Depression, 3, 52-73. doi: 10.4236/ojd.2014.32011.

[1]   Aebischer, C. P., Schierle, J., & Schuep, W. (1999). Simultaneous Determination of Retinol, Tocopherols, Carotene, Lycopene and Xanthophylls in Plasma by Means of Reversed-Phase High-Performance Liquid Chromatography. Methods in Enzymology, 299, 348-362.

[2]   Andreazza, A. C., Kauer-Sant’anna, M., Frey, B. N., Bond, D. J., Kapczinski, F., Young, L. T., & Yatham, L. N. (2008). Oxidative Stress Markers in Bipolar Disorder: A Meta-Analysis. Journal of Affective Disorders, 111, 135-144.

[3]   Angst, J., Azorin, J. M., Bowden, C. L., Perugi, G., Vieta, E., Gamma, A., Young, A. H., & BRIDGE Study Group (2011). Prevalence and Characteristics of Undiagnosed Bipolar Disorders in Patients with a Major Depressive Episode: The BRIDGE Study. JAMA Psychiatry, 68, 791-798.

[4]   Bellivier, F., Yon, L., Luquiens, A., Azorin, J. M., Bertsch, J., & Gerard, S. (2011). Suicidal Attempts in Bipolar Disorder: Results from an Observational Study (EMBLEM). Bipolar Disorders, 13, 377-386.

[5]   Berk, M., Dean, O., Cotton, S. M., Gama, C. S., Kapczinski, F., Fernandes, B. S. et al. (2011). The Efficacy of N-Acetylcysteine as an Adjunctive Treatment in Bipolar Depression: An Open Label Trial. Journal of Affective Disorders, 135, 389-394.

[6]   Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., Magalhaes, P. V. S., Amminger, P., McGorry, P., & Malh, G. S. (2011). Pathways Underlying Neuroprogression in Bipolar Disorder: Focus on Inflammation, Oxidative Stress and Neurotrophic Factors. Neuroscience & Biobehavioral Reviews, 35, 804-817.

[7]   Bilici, M., Efe, H., Koroglu, M. A., Uydu, H.A., Bekaroglu, M., & Deger, O. (2001). Antioxidative Enzyme Activities and Lipid Peroxidation in Major Depression: Alterations by Antidepressant Treatments. Journal of Affective Disorders, 64, 43-51.

[8]   Bowden, C. L. (2001). Strategies to Reduce Misdiagnosis of Bipolar Depression. Psychiatric Services, 52, 51-55.

[9]   Britt, S. G., Chiu, V. W., Redpath, G. T., & VandenBerg, S. R. (1992). Elimination of Ascorbic Acid-Induced Membrane Lipid Peroxidation and Serotonin Receptor Loss by Trolox-C, a Water Soluble Analogue of Vitamin E. Journal of Receptor Research, 12, 181-200.

[10]   Camacho, A., & Dimsdale, J. E. (2000). Platelets and Psychiatry: Lessons Learned from Old and New Studies. Psychosomatic Medicine, 62, 326-336.

[11]   Cocchi, M., Tonello, L., Cappello, G., Tarozzi, G., Nabacino, L., Pastorini, E., Bucciarelli, S., Solazzo, L., De luca, M., Visci, G., & Caramia, G. (2008). Membrane Platelet Fatty Acids: Biochemical Characterisation of the Ischemic Cardiovascular Disease, Characteristics of the Paediatric Age, through an Artificial Neural Network Interpretation. Medical and Surgical Pediatrics, 30, 25-30.

[12]   Cocchi, M., Gabrielli, F., Tonello, L., & Pregnolato, M. (2010). The Interactome Hypothesis of Depression. NeuroQuantology, 8, 603-613.

[13]   Cocchi, M., Sardi, L., Tonello, L., & Martelli, G. (2009). Do Mood Disorders Play a Role on Pig Welfare? Italian Journal of Animal Science, 8, 691-704.

[14]   Cocchi, M., & Tonello, L. (2006). Biological, Biochemical and Mathematical Considerations about the Use of an Artificial Neural Network (ANN) for the Study of the Connection between Platelet Fatty Acids and Major Depression. Journal of Biological Research, 81, 82-87.

[15]   Cocchi, M., & Tonello, L. (2007). Platelets, Fatty Acids, Depression and Cardiovascular Ischemic Pathology. Progress in Nutrition, 9, 94-104.

[16]   Cocchi, M., & Tonello, L. (2010a). Bio Molecular Considerations in Major Depression and Ischemic Cardiovascular Disease. Central Nervous System Agents in Medicinal Chemistry, 10, 97-107.

[17]   Cocchi, M., & Tonello, L. (2010b). Running the Hypothesis of a Bio Molecular Approach to Psychiatric Disorder Characterization and Fatty Acids Therapeutical Choices. Annals of General Psychiatry, 9, S26.

[18]   Cocchi, M., Tonello, L., & Cappello, G. (2006). Biochemical Markers in Major Depression as Interface between Neuronal Network and Artificial Neural Network (ANN). Journal of Biological Research, 81, 77-81.

[19]   Cocchi, M., Tonello, L., De Lucia, A., & Amato, P. (2009a). Platelet and Brain Fatty Acids: A Model for the Classification of the Animals? Part 1. International Journal of Anthropology, 24, 69-76.

[20]   Cocchi, M., Tonello, L., De Lucia, A., & Amato, P. (2009b). Platelet and Brain Fatty Acids: A Model for the Classification of the Animals? Part 2. Platelet and Brain Fatty Acid Transfer: Hypothesis on Arachidonic Acid and Its Relationship to Major Depression. International Journal of Anthropology, 24, 201-220.

[21]   Cocchi, M., Tonello, L., & Gabrielli, F. (2012). Considerations on Blood Platelets: A Neuron’s Mirror for Mood Disorders? Open Journal of Blood Diseases, 2, 22-29.

[22]   Cocchi, M., Tonello, L., & Lercker, G. (2010). Fatty Acids, Membrane Viscosity, Serotonin and Ischemic Heart Disease. Lipids in Health and Disease, 9, 97.

[23]   Cocchi, M., Tonello, L., & Rasenick, M. (2010). Human Depression: A New Approach in Quantitative Psychiatry. Annals of General Psychiatry, 9, 25.

[24]   Cocchi, M., Tonello, L., Tsaluchidu, S., & Puri, B. K. (2008). The Use of Artificial Neural Networks to Study Fatty Acids in Neuropsychiatric Disorders. BMC Psychiatry, 8, S3.

[25]   Da Prada, M., Cesura, A. M., Launay, J. M., & Richards, J. G. (1988). Platelets as a Model for Neurones? Experientia, 44, 115-126.

[26]   Dionisio, N., Jardín, I., Salido, G. M., & Rosado, J. A. (2010). Homocysteine, Intracellular Signaling and Thrombotic Disorders. Current Medicinal Chemistry, 17, 3109-3119.

[27]   Donati, R. J., Dwivedi, Y., Roberts, R. C., Conley, R. R., Pandey, G. N., & Rasenick, M. M. (2008). Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gs Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase. Journal of Neuroscience, 28, 3042-3050.

[28]   Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctot, K. L. (2010). A Meta-Analysis of Cytokines in Major Depression. Biological Psychiatry, 67, 446-457.

[29]   Engelberg, H. (1992). Low Serum Cholesterol and Suicide. Lancet, 339, 727-729.

[30]   Evers, C. A., & Starr, L. (2006). Biology: Concepts and Applications (6th ed.). Thomson.

[31]   Folch, J., Less, M., & Sloane Stanley, G. H. (1957). A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissue. Journal of Biological Chemistry, 226, 497-509.

[32]   Fountoulakis, K. N. (2010). Pharmaceutical Treatment of Acute Bipolar Depression. F1000 Medicine Report 2.

[33]   Frasure-Smith, N., & Lespérance, F. (2006). Depression and Coronary Artery Disease. Heart, 31, 64-68.

[34]   Goldstein, B. I., Kemp, D. E., Soczynska, J. K., & McIntyre, R. S. (2009). Inflammation and the Phenomenology, Pathophysiology, Comorbidity, and Treatment of Bipolar Disorder: A Systematic Review of the Literature. Journal of Clinical Psychiatry, 70, 1078-1090.

[35]   Heron, D. S., Shinitzky, M., Hershkowitz, M., & Samuel, D. (1980). Lipid Fluidity Markedly Modulates the Binding of Serotonin to Mouse Brain Membranes. Proceedings of the National Academy of Sciences of the United States of America, 77, 7463-7467.

[36]   Khairova, R., Pawar, R., Salvadore, G., Juruena, M. F., De Sousa, R. T., Soeiro-De-Souza, M. G., Salvador, M., Zarate, C. A., Gattaz, W. F., & Machado-Vieira, R. (2012). Effects of Lithium on Oxidative Stress Parameters in Healthy Subjects. Molecular Medicine Reports, 5, 680-682.

[37]   Kohonen, T. (2001). Self-Organizing Maps (3rd ed.). Berlin: Springer.

[38]   Kulkarni, S. K., Bhutani, M. K., & Bishnoi, M. (2008). Antidepressant Activity of Curcumin: Involvement of Serotonin and Dopamine System. Psychopharmacology, 201, 435-442.

[39]   Lee, R. E. (1985). Membrane Engineering to Rejuvenate the Ageing Brain. Canadian Medical Association Journal, 132, 325-327.

[40]   Leonard, B. (2000). Clinical Implications of Mechanisms of Action of Antidepressants. Advances in Psychiatric Treatment, 6, 178-186.

[41]   Maes, M., Galecki, P., Chang, Y. S., & Berk, M. (2011). A Review on the Oxidative and Nitrosative Stress (O&NS) Pathways in Major Depression and Their Possible Contribution to the (Neuro) Degenerative Processes in that Illness. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35, 676-692.

[42]   Maes, M., Mihaylova, I., Kubera, M., Uytterhoeven, M., Vrydags, N., & Bosmans, E. (2010). Increased Plasma Peroxides and Serum Oxidized Low Density Lipoprotein Antibodies in Major Depression: Markers that Further Explain the Higher Incidence of Neurodegeneration and Coronary Artery Disease. Journal of Affective Disorders, 125, 287-294.

[43]   Mann, J. J. (2003). Neurobiology of Suicidal Behaviour. Nature Reviews Neuroscience, 4, 819-828.

[44]   Mann, J. J., & Currier, D. M. (2010). Stress, Genetics and Epigenetic Effects on the Neurobiology of Suicidal Behavior and Depression. European Psychiatry, 25, 268-271.

[45]   Marangos, P. J., Campbell, I. C., Schmechel, D. E., Murphy, D. L., & Goodwin, F. K. (1980). Blood Platelets Contain a Neuron-Specific Enolase Subunit. Journal of Neurochemistry, 34, 1254-1258.

[46]   Mathews, D. C., Richards, E. M., Niciu, M. J., Ionescu, D. F., Rasimas, J. J., & Zarate Jr., C. A. (2013). Neurobiological Aspects of Suicide and Suicide Attempts in Bipolar Disorder. Translational Neuroscience, 4, 203-216.

[47]   Mazza, M., Di Nicola, M., Janiri, L., & Bria, P. (2013). To Be or Not to Be a Bipolar Disorder Patient: Problems with Diagnosis. Journal of Nervous & Mental Disease, 201, 435-437.

[48]   McNamara, R. K., & Lotrich, F. E. (2012). Elevated Immune-Inflammatory Signaling in Mood Disorders: A New Therapeutic Target? Expert Review of Neurotherapeutics, 12, 1143-1161.

[49]   Milaneschi, Y., Bandinelli, S., Penninx, B. W., Corsi, A. M., Lauretani, F., Vazzana, R. et al. (2012). The Relationship between Plasma Carotenoids and Depressive Symptoms in Older Persons. World Journal of Biological Psychiatry, 13, 588-598.

[50]   Mitra, S., Goyal, T., & Mehta, J. L. (2011). Oxidized LDL, LOX-1 and Atherosclerosis. Cardiovascular Drugs and Therapy, 25, 419-429.

[51]   Ng, F., Berk, M., Dean, O., & Bush, A. I. (2008). Oxidative Stress in Psychiatric Disorders: Evidence Base and Therapeutic Implications. International Journal of Neuropsychopharmacology, 11, 851-876.

[52]   Nicholson, A. M., & Ferreira, A. (2009). Increased Membrane Cholesterol Might Render Mature Hippocampal Neurons More Susceptible to Beta-Amyloid-Induced Calpain Activation and tau Toxicity. Journal of Neuroscience, 29, 4640-4651.

[53]   Ozcan, M. E., Gulec, M., Ozerol, E., Polat, R., & Akyol, O. (2004). Antioxidant Enzyme Activities and Oxidative Stress in Affective Disorders. International Clinical Psychopharmacology, 19, 89-95.

[54]   Pandey, G. N. (2011). Neurobiology of Adult and Teenage Suicide. Asian Journal of Psychiatry, 4, 2-13.

[55]   Pandey, G. N., & Dwivedi, Y. (2012). Peripheral Biomarkers for Suicide, In Y. Dwivedi (Ed.), The Neurobiological Basis of Suicide (pp. 407-424). Boca Raton, FL: CRC Press.

[56]   Pandya, C. D., Howell, K. R., & Pillai, A. (2012). Antioxidants as Potential Therapeutics for Neuropsychiatric Disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 46, 214-223.

[57]   Phillips, M. L., & Kupfer, D. J. (2013). Bipolar Disorder Diagnosis: Challenges and Future Directions. Lancet, 381, 1663-1671.

[58]   Plein, H., & Berk, M. (2001). The Platelet as a Peripheral Marker in Psychiatric Illness. Human Psychopharmacology, 16, 229-236.

[59]   Pletscher, A., & Laubscher, A. (1980). Blood Platelets as Models for Neurons: Uses and Limitations. Journal of Neural Transmission Supplementum, 16, 7-16.

[60]   Rawdin, B. J., Mellon, S. H., Dhabhar, F. S., Epel, E. S., Puterman, E., Su, Y., Burke, H. M., Reus, V. I., Rosser, R., Hamilton, S. P., Nelson, J. C., & Wolkowitz, O. M. (2012). Dysregulated Relationship of Inflammation and Oxidative Stress in Major Depression. Brain, Behavior, and Immunity, 31, 143-152.

[61]   Sachs, G. S. (1996). Bipolar Mood Disorder: Practical Strategies for Acute and Maintenance Phase Treatment. Journal of Clinical Psychopharmacology, 16, 32S-47S.

[62]   Scapagnini, G., Davinelli, S., Drago, F., De Lorenzo, A., & Oriani, G. (2012). Antioxidants as Antidepressants: Fact or Fiction? CNS Drug, 26, 477-490.

[63]   Smith, D. J., Griffiths, K. M., Hood, K., Craddock, N., & Simpson, S. A. (2011). Unrecognised Bipolar Disorder in Primary Care Patients with Depression. British Journal of Psychiatry, 199, 49-56.

[64]   Stahl, S. M., Woo, D. J., Mefford, I. N., Berger, P. A., & Ciaranello, R. D. (1983). Hyperserotonemia and Platelet Serotonin Uptake and Release in Schizophrenia and Affective Disorders. American Journal of Psychiatry, 140, 26-30.

[65]   Stanley, M., & Stanley, B. (1989). Biochemical Studies in Suicide Victims: Current Findings and Future Implications. Suicide and Life-Threatening Behavior, 19, 30-42.

[66]   Stanley, M., Stanley, B., Traskman-Bendz, L., Mann, J. J., & Meyendorff, E. (1986). Neurochemical Findings in Suicide Completers and Suicide Attempters. Suicide and Life-Threatening Behavior, 16, 286-300.

[67]   Steckert, A. V., Valvassori, S. S., Moretti, M., Dal-Pizzol, F., & Quevedo, J. (2010). Role of Oxidative Stress in the Pathophysiology of Bipolar Disorder. Neurochemical Research, 35, 1295-1301.

[68]   Suppes, T., Datto, C., Minkwitz, M., Nordenhem, A., Walker, C., & Darko, D. (2010). Effectiveness of the Extended Release Formulation of Quetiapine as Monotherapy for the Treatment of Acute Bipolar Depression. Journal of Affective Disorders, 121, 106-115.

[69]   Tonello, L., & Cocchi, M. (2010). The Cell Membrane: Is It a Bridge from Psychiatry to Quantum Consciousness? Neuro-Quantology, 8, 54-60.

[70]   Turecki, G. (2001). Suicidal Behavior: Is There a Genetic Predisposition? Bipolar Disorders, 3, 335-349.

[71]   Turecki, G., Ernst, C., Jollant, F., Labonte, B., & Mechawar, N. (2012). The Neurodevelopmental Origins of Suicidal Behavior. Trends in Neurosciences, 35, 14-23.

[72]   Undurraga, J., Baldessarini, R. J., Valenti, M., Pacchiarotti, I., & Vieta, E. (2012). Suicidal Risk Factors in Bipolar I and II Disorder Patients. Journal of Clinical Psychiatry, 73, 778-782.

[73]   Yager, S., Forlenza, M. J., & Miller, G. E. (2010). Depression and Oxidative Damage to Lipids. Psychoneuroendocrinology, 35, 1356-1362.