LETTERS

sensitivity: an exploratory clinical study. Aliment Pharmacol Ther 2014; 39:1104–1112 5. Catassi C, Bai JC, Bonaz B, et al: Non-celiac gluten sensitivity: the new frontier of gluten related disorders. Nutrients 2013; 5:3839–3853 Bernardo Dell’Osso, M.D. Luca Elli, M.D. From the Department of Mental Health, Department of Pathophysiology and Transplant, University of Milan, Milan, Italy; the Center for the Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; and the Bipolar Disorders Clinic, Stanford University, Stanford, Calif. Dr. Elli is a member of the Dr. Schär Institute Board. Dr. Dell’Osso reports no financial relationships with commercial interests. This letter was accepted for publication in April 2015.

can modify the patient’s schizophrenic illness to increase expression of depressive symptoms. Although there is some recent evidence linking major depressive disorder to celiac disease or gluten sensitivity (7, 8), the evidence does not have the long history and series of replications found in the literature on schizophrenia (9). We agree with the authors of the letter that celiac disease has been associated with psychiatric disorders other than schizophrenia, including major depressive disorder. With all this taken into account, we also agree with the authors that a gluten-free diet should be investigated in psychiatric disorders that show evidence of an association with celiac disease or gluten sensitivity.

Am J Psychiatry 2015; 172:685–686; doi: 10.1176/appi.ajp.2015.15030361

Response to Dell’Osso and Elli TO THE EDITOR: We thank Drs. Dell’Osso and Elli for their critical interest in our article. They raise the issue of an “affective diathesis rather than schizophrenia” in the patient we reported on in our clinical case conference. They base their critique upon the patient’s history of depressive symptoms, hallucinations, and delusions as well as a family history of seasonal affective disorder in his parents and bouts of depression in his grandparents. Depressive symptoms have been recognized as a feature of schizophrenia since Bleuler described them as either directly springing from the very process of the malady (i.e., primary symptoms) or as secondary symptoms of schizophrenia, stating that “chronic as well as acute depressions are found more frequently in the beginning of an outspoken illness than any other syndrome” (1). Kraepelin lists among the clinical forms of dementia praecox “simple depressive dementia” and “delusional depressive dementia” (2). In longitudinal populationbased studies, the diagnosis of schizophrenia is often preceded by another diagnosis that is often affective in nature. In longitudinal studies, up to one-third of patients who initially had a diagnosis other than schizophrenia were later diagnosed with schizophrenia (3, 4). Depressive symptoms in patients with schizophrenia can be observed during each phase of the disorder including the prodromal phase. It is important to note that in our case, depressive symptoms presented at age 15 in conjunction with psychotic symptoms in the context of his “first break” that caused the patient’s first hospitalization and a diagnosis of major depression with psychotic features. Depressive symptoms in the early course of schizophrenia have been associated with a family history of unipolar depression or psychiatric disorders other than schizophrenia (5, 6). A familial genetic liability to affective disorder, as in the case we have presented,

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REFERENCES 1. Bleuler E: Dementia Praecox or the Group of Schizophrenias. Madison, Conn, International University Press, 1964 2. Kraepelin E: Dementia Praecox and Paraphrenia (Lifetime Editions of Kraepelin in English). Bristol, United Kingdom, Thoemmes Press, 2000 3. Chen YR, Swann AC, Burt DB: Stability of diagnosis in schizophrenia. Am J Psychiatry 1996; 153:682–686 4. Bromet EJ, Kotov R, Fochtmann LJ, et al: Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry 2011; 168:1186–1194 5. Subotnik KL, Nuechterlein KH, Asarnow RF, et al: Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness. Am J Psychiatry 1997; 154:1551–1556 6. Bottlender R, Strauss A, Möller HJ: Prevalence and background factors of depression in first admitted schizophrenic patients. Acta Psychiatr Scand 2000; 101:153–160 7. Peters SL, Biesiekierski JR, Yelland GW, et al: Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity: an exploratory clinical study. Aliment Pharmacol Ther 2014; 39:1104–1112 8. Karakuła-Juchnowicz H, Szachta P, Opolska A, et al: The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders. Nutr Neurosci (Epub ahead of print, Sept 30, 2014) 9. Kalaydjian AE, Eaton W, Cascella N, et al: The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand 2006; 113:82–90 William W. Eaton, Ph.D. Lian-Yu Chen, M.D. F. Curtis Dohan, Jr., M.D. Deanna L. Kelly, Pharm.D. Nicola Cascella, M.D. From the Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore; Taipei City Psychiatric Center, Taipei City Hospital, Taipei City, Taiwan; the Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis; the Treatment Research Program, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore; and Sheppard Pratt Hospital, Baltimore. The authors’ disclosures accompany the original article. This letter was accepted for publication in April 2015. Am J Psychiatry 2015; 172:686; doi: 10.1176/appi.ajp.2015.15030361r

Am J Psychiatry 172:7, July 2015

Response to Dell'Osso and Elli.

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