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Phospholipid Spectrum Disorders
in Psychiatry and Neurology

Second Edition

Edited by Malcolm Peet, Iain Glen and David Horrobin






List of contributors


Part I. Introduction and basic science


††††††††††††††† 1†††††† Phospholipid metabolism and the pathophysiology of psychiatric and

†††††††††††††††††††††††† neurological disorders.

†††††††††††††††††††††††† David F. Horrobin and Crispin N. Bennett


††††††††††††††† 2†††††† The role of plasmalogens in normal brain function and in neurological

†††††††††††††††††††††††† disorders.

†††††††††††††††††††††††† Akhlaq A. Farooqui and Lloyd A. Horrocks


††††††††††††††† 3†††††† Long chain polyunsaturated fatty acids and cognitive development

†††††††††††††††††††††††† in childhood.

†††††††††††††††††††††††† J. Stewart Forsyth and Peter Willatts


††††††††††††††† 4†††††† The role of fatty acids in synaptic growth and plasticity.

†††††††††††††††††††††††† Kentaro Murakami and Aryeh Routtenberg


††††††††††††††† 5†††††† The possible role of abnormal platelet-activating factor metabolism in

†††††††††††††††††††††††† psychiatric disorders.

†††††††††††††††††††††††† Kathleen Taylor


††††††††††††††† 6†††††† The possible roles of lipoxygenase metabolism in psychiatric and

†††††††††††††††††††††††† neurological disorders.

†††††††††††††††††††††††† Hari Manev and Tolga Uz



Part II. Schizophrenia: membrane and phospholipid metabolism


††††††††††††††† 7†††††† Phospholipid and fatty acid biochemistry in schizophrenia.

†††††††††††††††††††††††† David F. Horrobin


††††††††††††††† 8†††††† Phospholipase A2-associated processes in the human brain and their role in

†††††††††††††††††††††††† neuropathology and psychopathology.

†††††††††††††††††††††††† Brian M. Ross


††††††††††††††† 9†††††† Cytosolic phospholipase A2 (IVAPLA2) in red cells in schizophrenia and

†††††††††††††††††††††††† other psychiatric disorders.

†††††††††††††††††††††††† Alastair C. A. Glen, Donald J. Macdonald and Rose M. Boyle


††††††††††††††† 10†††† Abnormalities of fatty acid metabolism in red cells, platelets and brain in

†††††††††††††††††††††††† schizophrenia.

†††††††††††††††††††††††† Jeffrey K. Yao


††††††††††††††† 11†††† Phospholipase A2 and the hypofrontality hypothesis of schizophrenia.

†††††††††††††††††††††††† Wagner F. Gattaz, Juliana Yacubian, Hildeberto Tavares and

†††††††††††††††††††††††† Juergen Brunner


††††††††††††††† 12†††† Brain phospholipid metabolism in schizophrenia: assessment with

†††††††††††††††††††††††† 31P magnetic resonance spectroscopy.

†††††††††††††††††††††††† Peter C. Williamson and Dick J. Drost


††††††††††††††† 13†††† Magnetic resonance spectroscopy in the assessment of phospholipid

†††††††††††††††††††††††† metabolism in schizophrenia and other psychiatric disorders.

†††††††††††††††††††††††† Jay W. Pettegrew and Matcheri S. Keshavan, Jeffrey A. Stanley,

†††††††††††††††††††††††† Richard J. McClure, Cynthia R. Johnson and Kanagasabai Panchalingam


††††††††††††††† 14†††† The role of apolipoprotein D in the mechanisms of action of clozapine, and

†††††††††††††††††††††††† in psychiatric disorders.

††††††††††††††††††††††† Elizabeth A. Thomas and J. Gregor Sutcliffe


††††††††††††††† 15†††† The effects of antipsychotic drugs on membrane phospholipids: a possible

†††††††††††††††††††††††† novel mechanism of action of clozapine.

†††††††††††††††††††††††† David F. Horrobin


††††††††††††††† 16†††† The role of oxidative stress in modulating membrane and phospholipid

†††††††††††††††††††††††† function in schizophrenia.

†††††††††††††††††††††††† Sahebarao P. Mahadik, Vinay V. Parikh and Mohammad M. Khan


††††††††††††††† 17†††† Effects of antipsychotic drugs on rat brain, and on essential fatty acids in

†††††††††††††††††††††††† the erythrocytes of schizophrenic patients: implications for outcome.

†††††††††††††††††††††††† Sahebarao P. Mahadik, Mohammad M. Khan and Vinay Parikh


††††††††††††††† 18†††† Membrane protection in schizophrenia: concepts and therapeutic

†††††††††††††††††††††††† approaches.

†††††††††††††††††††††††† Ravinder Reddy and Jeffrey K. Yao


††††††††††††††† 19†††† Retinal function in schizophrenia.

†††††††††††††††††††††††† Malcolm Peet, Rhian Edwards, Fiona Skinner and Rachel Warner



Part III.†† Diagnostic tests in schizophrenia and

††††††††††††††† other psychiatric disorders


††††††††††††††† 20†††† Oral and topical niacin flush test.

†††††††††††††††††††††††† Brian M. Ross, Pauline E. Ward, Roderick McLean and Iain Glen


††††††††††††††† 21†††† The niacin skin-flush response in patients with schizophrenia, unaffected

†††††††††††††††††††††††† first-degree relatives and controls.

†††††††††††††††††††††††† Stella Fabrikant, Brendan Jansen, Joachim Hallmayer, Adam Brett,

†††††††††††††††††††††††† Julie Johnston and Assen Jablensky


††††††††††††††† 22†††† The niacin skin-flush test in unmedicated schizophrenic patients, their

†††††††††††††††††††††††† first degree relatives, and depressive patients.

†††††††††††††††††††††††† Malcolm Peet, Sandeep Shah and Rhian W. Edwards


††††††††††††††† 23†††† Niacin flush response in families of schizophrenic patients.

†††††††††††††††††††††††† Merilyn C. Waldo


††††††††††††††† 24†††† Niacin testing in other psychiatric and neurological disorders.

†††††††††††††††††††††††† Basant K. Puri


††††††††††††††† 25†††† Markers of oxidative damage in exhalant and their use in schizophrenia

†††††††††††††††††††††††† and other disorders.

††††††††††††††††††††††† Iain Glen, Ivor McKenzie, Kemi Obajimi, George H. Dodd,

††††††††††††††††††††††† Pauline E. Ward and Brian M. Ross



Part IV. Schizophrenia: treatment and the effect of diet


††††††††††††††† 26†††† Dietary fat and schizophrenia.

†††††††††††††††††††††††† Malcolm Peet


††††††††††††††† 27†††† Eicosapentaenoic acid derivatives in the management of schizophrenia.

†††††††††††††††††††††††† David F. Horrobin


††††††††††††††† 28†††† Long-term follow up of a single patient with schizophrenia treated with

†††††††††††††††††††††††† ethyl-EPA alone.

†††††††††††††††††††††††† Basant K. Puri and Alexandra J. Richardson


††††††††††††††† 29†††† The use of n-3 fatty acids for the management of depression andpsychosis

†††††††††††††††††††††††† during pregnancy and breast feeding.

†††††††††††††††††††††††† Kuan-Pin Su, Winston W. Shen and Shih-Yi Huang



Part V. Depression, anxiety and bipolar disorder


††††††††††††††† 30†††† Relationship between brain lipids, depression and suicide.

†††††††††††††††††††††††† Malcolm Peet and Crispin N. Bennett


††††††††††††††† 31†††† Roles of abnormalities of phospholipid metabolism in bipolar disorder.

†††††††††††††††††††††††† David F. Horrobin


††††††††††††††† 32†††† Effects of n3 fatty acids on depressive symptoms induced by

†††††††††††††††††††††††† proinflammatory cytokines in animals.

†††††††††††††††††††††††† Cai Song


††††††††††††††† 33†††† Fatty acid composition in major depression.

†††††††††††††††††††††††† Dirk van West and Michael Maes


††††††††††††††† 34†††† The relationship between depression and medical illness.

†††††††††††††††††††††††† Malcolm Peet and David F. Horrobin


††††††††††††††† 35†††† Mechanisms of action of mood-stabilizing drugs.

†††††††††††††††††††††††† Miguel A. Contreras, Jyrki J. O. Rintala and Michael C. J. Chang


††††††††††††††† 36†††† The role of essential lipids in the management of bipolar disorder.

†††††††††††††††††††††††† Ingrid A. Sarmiento, Andrew L. Stoll and Bruce Cohen


††††††††††††††† 37†††† N-3 fatty acids in the treatment of depression.

†††††††††††††††††††††††† Malcolm Peet, Rhian Edwards and David F. Horrobin


††††††††††††††† 38†††† Treatment of panic disorder with moderate-to-severe palpitations using

†††††††††††††††††††††††† essential fatty acids.

†††††††††††††††††††††††† Krishna S. Vaddadi



Part VI. Dyslexia, dyspraxia and schizotypy


††††††††††††††† 39†††† Clinical and biochemical fatty acid abnormalities in dyslexia, dyspraxia

†††††††††††††††††††††††† and schizotypy: an overview.

†††††††††††††††††††††††† Alexandra J. Richardson, Eva Cyhlarova and Basant K. Puri


††††††††††††††† 40†††† Clinical trials of fatty acid supplementation in dyslexia and dyspraxia.

†††††††††††††††††††††††† Alexandra J. Richardson


††††††††††††††† 41†††† Magnetic resonance spectroscopy in the assessment of brain phospholipid

†††††††††††††††††††††††† metabolism in dyslexia.

††††††††††††††††††††††† Basant K. Puri and Alexandra J. Richardson



Part VII. Paediatric psychiatry


††††††††††††††† 42†††† Essential fatty acids in relation to attention deficit hyperactivity disorder:

†††††††††††††††††††††††† an update.

†††††††††††††††††††††††† John R. Burgess and Laura J. Stevens


††††††††††††††† 43†††† Abnormal fatty acid metabolism in autism and Aspergerís syndrome.

†††††††††††††††††††††††† J. Gordon Bell, J. R. Dick, E. E. MacKinlay, A. C. A. Glen,

†††††††††††††††††††††††† D. J. Macdonald, R. M. Boyle and D. V. Riordan


††††††††††††††† 44†††† Clinical trials of fatty acid supplementation in attention deficit

†††††††††††††††††††††††† hyperactivity disorder.

†††††††††††††††††††††††† Alexandra J. Richardson


††††††††††††††† 45†††† A possible role for fatty acid treatment in paediatric depression.

†††††††††††††††††††††††† Basant K. Puri



Part VIII. Movement disorders and Huntingtonís disease


††††††††††††††† 46†††† Transgenic and other models of Huntingtonís disease: focus on lipid

†††††††††††††††††††††††† modulation.

†††††††††††††††††††††††† Jeremiah J. Clifford, John L. Waddington, John Drago and

†††††††††††††††††††††††† Krishna S. Vaddadi


††††††††††††††† 47†††† Essential fatty acids in the treatment of Huntingtonís disease.

†††††††††††††††††††††††† Krishna S. Vaddadi


††††††††††††††† 48†††† A randomised trial of ethyl eicosapentaenoate in patients with end-stage

†††††††††††††††††††††††† Huntingtonís disease.

†††††††††††††††††††††††† Basant K. Puri



Part IX. Alzheimerís disease


††††††††††††††† 49†††† Phospholipase A2 activity in Alzheimerís disease.

†††††††††††††††††††††††† Wagner F. Gattaz, Orestes V. Forlenza and Cassio M. C. Bottino


††††††††††††††† 50†††† The role of phospholipid metabolism during normal brain ageing and

†††††††††††††††††††††††† radiation-accelerated neurodegeneration.

†††††††††††††††††††††††† Marina Lynch and David F. Horrobin



Part X. Genetics and evolution


††††††††††††††† 51†††† Locations of genes for phospholipid and fatty acid related proteins as

†††††††††††††††††††††††† compared to those associated with psychiatric disorders.

†††††††††††††††††††††††† Crispin N. Bennett and David F. Horrobin


††††††††††††††† 52†††† A speculative overview: the relationship between phospholipid spectrum

†††††††††††††††††††††††† disorders and human evolution.

†††††††††††††††††††††††† David F. Horrobin

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