Archives of General Psychiatry

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250004001

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1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250010002

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables.

Mannuzza, Salvatore;Klein, Rachel Gittelman;Bonagura, Noreen;Konig, Paula Horowitz;Shenker, Ronald

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250017003pmid: 3337607

Abstract • In a previous article we reported the rate of DSM-III diagnoses among 101 male adolescents (aged 16 to 23 years) in whom hyperactivity had been diagnosed between ages 6 and 12 years compared with 100 controls. This report examines the rates of dysfunction among the 52 probands and 80 control adolescents who did not receive a DSM-III diagnosis at followup. Contrary to expectations, there were few areas (primarily involving school adjustment) in which the formerly hyperactive children were found to be at a disadvantage and numerous areas (occupational adjustment, temperament, alcohol abuse, antisocial activities, etc) in which the groups were indistinguishable. The results are explained in accordance with a bimodal distribution of dysfunction in hyperactive children grown up. Indirectly, this model supports the construct validity of the DSM-III diagnoses attention deficit disorder with hyperactivity, substance use disorder, and antisocial personality disorder. Post hoc analyses suggest that behavior problems resulting from drug use in early adolescence have graver consequences for previously hyperactive children than normal subjects. References 1. Gittelman R, Mannuzza S, Shenker R, Bonagura N: Hyperactive boys almost grown up: I. Psychiatric status . Arch Gen Psychiatry 1985;42:937-947.Crossref 2. Weiss G, Hechtman L, Perlman T, Hopkins J, Wener A: Hyperactives as young adults: A controlled prospective ten-year follow-up of 75 children . Arch Gen Psychiatry 1979;36:675-681.Crossref 3. Weiss G, Hechtman L, Milroy T, Perlman T: Psychiatric status of hyperactives as adults: A controlled prospective 15-year follow-up of 63 hyperactive children . J Am Acad Child Psychiatry 1985;24:211-220.Crossref 4. Robins LN, Helzer JE, Croughan J, Ratcliff KS: The NIMH Diagnostic Interview Schedule: Its history, characteristics, and validity . Arch Gen Psychiatry 1981;38:381-389.Crossref 5. Robins LN, Helzer JE, Ratcliff KS, Seyfried W: Validity of the Diagnostic Interview Schedule, version II: DSM-III diagnoses . Psychol Med 1982;12:855-870.Crossref 6. Gittelman R, Mannuzza S: Diagnosing ADD-H in adolescents . Psychopharmacol Bull 1985;21:237-242.

Schiavi, Raul C.;Theilgaard, Alice;Owen, David R.;White, Daniel

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250023004pmid: 3122695

Abstract • Behavioral investigation of men with sex chromosome anomalies has been primarily limited to the study of institutionalized individuals or patient groups. A double-blind controlled investigation of XYY and XXY men found in a birth cohort of 4591 tall men born in Copenhagen gathered sexual information and assessed the role of hormonal determinants on sexual behavior. There were significant differences in several sexual dimensions and in gender role between XYY men and their controls and XXY men and their controls as well as between XYY and XXY men. Although both proband groups differed from each other and from their controls in pituitary gonadal function, there was no evidence that adult hormonal levels mediate the effect of sex chromosome anomalies on male sexuality. References 1. Owen DR: The 47,XYY male: A review . Psychol Bull 1972;78:209-233.Crossref 2. Hook EB: Behavioral implications of the human XYY genotype . Science 1973;179:139-150.Crossref 3. Borgaonkar SD, Shah SA: The XYY chromosome: Male or syndrome? Prog Med Genet 1974;10:135-222. 4. Walzer S, Gerald PS, Shah SA: The XYY genotype . Annu Rev Med 1978;29:563-570.Crossref 5. Court Brown WM, Price WH, Jacobs PA: Further information on the identity of 47,XYY males . Br Med J 1968;2:325-328.Crossref 6. Griffith AW, Richards BW, Zaremba J, Abramowics T, Stewart A: Psychological and sociological investigation of XYY prisoners . Nature 1970;227:290-292.Crossref 7. Marinello MJ, Berkson RA, Edwards JA, Bannerman RM: A study of the XYY syndrome in tall men and juvenile delinquents . JAMA 1969;208:321-325.Crossref 8. Money J, Gaskin RJ, Hull H: Impulse, aggression and sexuality in the XYY syndrome . St Johns Law Rev 1969;44:220-235. 9. Buhrich N, Barr R, Lam-Po-Tang PRLC: Two transsexuals with 47-XYY karyotype . Br J Psychiatry 1978;133:77-81.Crossref 10. Raboch J, Mellan J, Starka L: Klinefelter's syndrome: Sexual development and activity . Arch Sex Behav 1979;8:333-339.Crossref 11. Bancroft J, Axworthy D, Ratcliffe S: The personality and psychosexual development of boys with 47 XXY chromosome constitution . J Child Psychol Psychiatry 1982;23:169-180.Crossref 12. Paulsen CA, Gordon DL, Carpenter RW, Candy HM, Drucker WD: Klinefelter's syndrome and its variants in a hormonal and chromosome study . Recent Prog Horm Res 1968;24:321-353. 13. Becker KL: Clinical and therapeutic experiences with Klinefelter's syndrome . Fertil Steril 1972;23:568-578. 14. Wakeling A: Comparative study of psychiatric patients with Klinefelter's syndrome and hypogonadism . Psychol Med 1972;2:139-143.Crossref 15. Witkin HA, Mednick SA, Schulsinger F, Bakkestrom E, Christiansen KO, Goodenough DR, Hirschhorn K, Lundsteen C, Owen DR, Philip J, Rubin DB, Stocking M: Criminality in XYY and XXY men . Science 1976;193:547-555.Crossref 16. Schiavi RC, Owen D, Fogel M, White D, Szechter R: Pituitary gonadal function in XYY men and XXY men identified in a population survey . Clin Endocrinol 1978;9:223-239.Crossref 17. Schiavi RC, Theilgaard A, Owen DR, White D: Sex chromosome anomalies, hormones and aggressivity . Arch Gen Psychiatry 1984;41:93-99.Crossref 18. Schafer R: The Clinical Application of Psychological Tests . New York, International University Press, 1951. 19. Rapaport D, Gill MM, Schafer R: The thematic apperception test , in Holt R (ed): Diagnostic Psychological Testing . New York, International University Press, 1968, pp 464-515. 20. Swensen C, Newton KR: The development of sexual differentiation on the Draw-a-Person Test . J Clin Psychol 1955;11:417-419.Crossref 21. Theilgaard A: A psychological study of the personalities of XYY and XXY men . Acta Psychiatr Scand Suppl 1984;69:1-133. 22. Davidson M, Toporek J: General univariate and multivariate analysis of variance and covariance, including repeated measures (URWAS) , in Dixon WJ (ed): Biomedical Computer Program P-Series . Los Angeles, University of California Press, 1980, pp 264-287. 23. Balodimos MC, Lisco H, Irwin I, Merrill W, Dingman JF: XYY karyotype in a case of familial hypogonadism . J Clin Endocrinol Metab 1966;26:443-452.Crossref 24. Nielsen J: Y chromosomes in male psychiatric patients above 180 cm tall . Br J Psychiatry 1968;114:1589-1590.Crossref 25. Nielsen J, Christensen AL, Schultz-Larsen J, Yde H: A psychiatricpsychological study of patients with the XYY syndrome found outside of institutions . Acta Psychiatr Scand 1973;49:159-168.Crossref 26. Zeuthen E, Hansen M, Christensen AL, Nielsen J: A psychiatricpsychological study of XYY males found in a general male population . Acta Psychiatr Scand 1975;51:3-18.Crossref 27. Raboch J, Starka L: Reported coital activity of men and levels of plasma testosterone . Arch Sex Behav 1973;2:309-316.Crossref 28. Money J, Annecillo C, Van Orman B, Borgaonkar DS: Cytogenetics, hormones and behavior disability: Comparison of XYY and XXY syndromes . Clin Genet 1974;6:370-382.Crossref 29. Money J, Wiedeking C, Walker P, Migeon C, Meyer W, Borgaonkar D: 47,XYY and 46,XY males with antisocial and/or sex-offending behavior: Antiandrogen therapy plus counseling . Psychoendocrinology 1975;1:165-178.Crossref 30. Davidson JM, Camargo CA, Smith ER: Effects of androgens on sexual behavior in hypogonadal men . J Clin Endocrinol Metab 1979;48:955-958.Crossref 31. Skakkebaek N, Bancroft J, Davidson DW, Warner P: Androgen replacement with oral testosterone undecanoate in hypogonadal men: A double-blind controlled study . Clin Endocrinol 1981;14:49-61.Crossref 32. Wu FCW, Bancroft J, Davidson DW, Nicol K: The behavioural effects of testosterone undecanoate in adult men with Klinefelter's syndrome: A controlled study . Clin Endocrinol 1982;16:489-497.Crossref 33. Schiavi RC, White D: Adrogens and male sexual function: A review of human studies . J Sex Marital Ther 1976;2:214-228.Crossref 34. Bancroft J: Endocrinology of sexual function . Clin Obstet Gynaecol 1980;7:253-281. 35. Harris RJ: A Primer of Multivariate Statistics , ed 2. Orlando, Fla, Academic Press Inc, 1985.

Reiss, Allan L.;Hagerman, Randi J.;Vinogradov, Sophia;Abrams, Micheal;King, Roy J.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250029005pmid: 3337608

Abstract • Fragile X syndrome, an X-linked genetic condition, is an important genetic cause of mental retardation in males. In addition to mental retardation, hemizygous males with fragile X syndrome appear to have a greater likelihood of displaying behaviors classified under the diagnostic category of pervasive developmental disorder than would be expected on the basis of mental retardation alone. Although the majority of female heterozygotes with the fragile X genetic defect are of normal intelligence, our clinical work with this population and a recent case report have suggested that females with fragile X syndrome have an increased rate of schizophrenia spectrum and affective disorders. In this study, the relationship of the fragile X genetic defect to psychopathology in female heterozygotes is investigated by psychiatric evaluation of 35 obligate female carriers of the fragile X chromosome and a comparison group of 24 fragile X—negative controls. Female fragile X carriers were found to have a greater frequency of psychopathology associated with schizophrenia spectrum diagnoses, particularly schizotypal features. A weaker association between the fragile X genetic defect and chronic affective disorders was detected. The specificity of the neuropsychiatric phenotype occurring in particular genetic conditions such as the fragile X syndrome adds a potentially valuable tool to the study of psychopathology in the general population. References 1. McKusick VA: Mendelian Inheritance in Man , ed 7. Baltimore, Johns Hopkins University Press, 1986. 2. Sutherland GR, Hecht F: Fragile Sites on Human Chromosomes . New York, Oxford University Press, 1985. 3. Ireland W: Mental Affections of Children . ed 2. New York, Churchill Livingstone Inc, 1900. 4. Martin JP, Bell Z: A pedigree of mental defect showing sex-linkage . J Neurol Psychiatry 1943;6:154-157.Crossref 5. Turner G, Opitz JM, Brown WT, Davies KE, Jacobs PA, Jenkins EC, Mikkelsen M, Partington MW, Sutherland GR: Conference report: Second international workshop on the fragile X and on X-linked mental retardation . Am J Med Genet 1986;23:11-68.Crossref 6. Opitz JM: On the gates of hell and a most unusual gene . Am J Med Genet 1986;23:1-10.Crossref 7. Lubs HA: A marker X chromosome . Am J Med Genet 1969;21:231-244. 8. Brown WT, Jenkins EC, Cohen IL, Fisch GS, Wolf-Schein EG, Gross A, Waterhouse L, Fein D, Mason-Brothers A, Ritro E, Ruttenberg BA, Bentley W, Castells S: Fragile X and autism: A multicenter survey . Am J Med Genet 1986;28:341-352.Crossref 9. Hagerman RJ, Jackson AW, Levitas A, Rimland B, Braden M: An analysis of autism in 50 males with the fragile X syndrome . Am J Med Genet 1986;23:359-374.Crossref 10. Kemper MB, Hagerman RJ, Ahmed RS, Mariner R: Cognitive profiles and the spectrum of clinical manifestations in heterozygous fra(X) females . Am J Med Genet 1986;23:139-156.Crossref 11. Fryns J: The female and the fragile X . Am J Med Genet 1986;23:157-170.Crossref 12. Hagerman RJ, Smith AC: The heterozygous female , in Hagerman RJ, McBogg PM (eds): The Fragile X Syndrome . Dillon, Colo, Spectra Publishing, 1983, pp 83-94. 13. Hagerman RJ, Chudley AE, Knoll JH, Jackson AW, Kemper M, Ahmed R: Autism in fragile X females . Am J Med Genet 1986;23:375-380.Crossref 14. Reiss AL, Feinstein C, Toomey KE, Goldsmith B, Rosenbaum K, Caruso MA: Psychiatric disability associated with the fragile X chromosome . Am J Med Genet 1986;23:393-402.Crossref 15. Jacobs P, Sherman S, Turner G, Webb T: The fragile (X) syndrome: The mutation problem . Am J Med Genet 1986;23:611-618.Crossref 16. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry 1978;35:837-844.Crossref 17. Andreasen NC, Grove WM, Shapiro RW, Keller MB, Hirschfield RM, McDonald-Scott P: Reliability of lifetime diagnosis: A multicenter collaborative perspective . Arch Gen Psychiatry 1981;38:400-405.Crossref 18. Leckman JF, Sholamskas D, Thompson WD: Best estimate of lifetime psychiatric diagnosis: A methodological study . Arch Gen Psychiatry 1982;39:879-883.Crossref 19. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria: Rationale and reliability . Arch Gen Psychiatry 1978;35:773-782.Crossref 20. Mannuzza S, Fryer AJ, Klein DF: Schedule for Affective Disorders and Schizophrenia—Lifetime Version, Rater Manual . New York, New York State Psychiatric Institute, 1985, pp 30-31. 21. Overall JE, Gorham DR: The Brief Psychiatric Rating Scale . Psychol Rep 1962;10;799-812.Crossref 22. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders—Diagnostic Manual , ed 3. New York, New York State Psychiatric Institute, 1981. 23. Delisi LE, White B, Reiss A, Gershon ES: Cytogenetic studies of schizophrenic patients, in Proceedings of the World Congresses of Biological Psychiatry. Pitman, NJ, Anthony Jannetti Co, 1985. 24. DeMeyer MK, Hingtgen JN, Jackson RK: Infantile autism reviewed: A decade of research . Schizophr Bull 1981;7:388-451.Crossref 25. Kenwrick S, Ionasescu V, Ionasescu G, Searby C, King A, Dubowitz M, Davies KE: Linkage studies of X-linked spastic paraplegia using DNA probes . Hum Genet 1986;73:264-266.Crossref 26. Mendelwicz J, Fleiss JL: Linkage studies with X-chromosome markers in bipolar (manic depressive) and unipolar (depressive) illness . Biol Psychiatry 1975;9:261-270. 27. Naidu S, Murphy M, Moser HW, Rett A: Rett syndrome: Natural history in 70 cases . Am J Med Genet 1986;24( (suppl 1) ):61-72.Crossref 28. Pennington BF, Bender B, Puck M, Salbenblatt J, Robinson A: Learning disabilities in children with sex chromosome anomalies . Child Dev 1982;53:1182-1192.Crossref 29. Money J, Alexander D: Turner's syndrome: Further demonstration of the presence of specific cognitional deficits . J Med Genet 1966;3:47-48.Crossref 30. Silbert A, Wolff DH, Lilienthal J: Spatial and temporal processing in patients with Turner's syndrome . Behav Genet 1977;7:11-21. 31. McCauley E, Ito J, Kay T: Psychosocial functioning in girls with Turner's syndrome and short stature: Social skills, behavior problems, and self-concept . J Am Acad Child Psychiatry 1986;25:105-112.Crossref 32. Overall JE, Hollister LE, Pichot P: Major psychiatric disorders: A four-dimensional model . Arch Gen Psychiatry 1967;16:146-151.Crossref

Gorman, Jack M.;Fyer, Minna R.;Goetz, Raymond;Askanazi, Jeffrey;Liebowitz, Michael R.;Fyer, Abby J.;Kinney, John;Klein, Donald F.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250035006pmid: 2827599

Abstract • Thirty-one patients with DSM-III panic disorder or agoraphobia with panic attacks, 13 normal controls, and 12 patients with other anxiety disorders were studied during ventilatory challenge with room air hyperventilation and 5% carbon dioxide inhalation. Patients also underwent sodium lactate infusion. Among the patients with panic disorder, 58% panicked with sodium lactate, 39% with 5% CO2, and 23% with room air hyperventilation. Of the other patients, four panicked with sodium lactate, none with 5% CO2, and one with room air hyperventilation. One normal control panicked with both sodium lactate and 5% CO2. Panic with CO2 was associated with an exaggerated ventilatory response and increases in plasma norepinephrine level and diastolic blood pressure. Patients with panic disorder may have hypersensitive CO2 receptors that, when triggered, evoke a subjective panic associated with an exaggerated ventilatory response and consequent hypocapnic alkalosis. References 1. Cohen ME, White PD: Life situations, emotions and neurocirculatory asthenia . Psychosom Med 1951;13:335-357.Crossref 2. Gorman JM, Askanazi J, Liebowitz MR, Fyer A, Stein J, Kinney JM, Klein DF: Response to hyperventilation in a group of patients with panic disorder . Am J Psychiatry 1984;41:857-861. 3. Woods SW, Charney DS, Lake J, Goodman WK, Redmond DE, Heninger DR: Carbon dioxide sensitivity in panic anxiety: Ventilatory and anxiogenic response to carbon dioxide in health subjects and panic anxiety patients before and after alprazolam treatment . Arch Gen Psychiatry 1986;43:900-909.Crossref 4. Read DJC: A clinical method for assessing the ventilatory response to carbon dioxide . Australas Ann Med 1967;16:20-32. 5. Griez E, van den Hout MA: Peripheral panic symptoms occur during changes in alveolar carbon dioxide . Compr Psychiatry 1985;26:381-387.Crossref 6. Van den Hout MA, Griez E: Panic symptoms after inhalation of CO2 . Br J Psychiatry 1984;144:503-507.Crossref 7. Van den Hout MA, Griez E: Cardiovascular and subjective response to inhalation of carbon dioxide . Psychother Psychosom 1982;37:75-82.Crossref 8. Lambertsen CJ: Neural control of respiration , in Mountcastle VS (ed): Medical Physiology . St Louis, CV Mosby Co, 1980, pp 1749-1773. 9. Mitchell RA, Loeschke HH, Severinghaus JW, Richardson BW, Massion WH: Regions of respiratory chemosensitivity on the surface of the medulla . Ann NY Acad Sci 1963;109:661-681.Crossref 10. Comroe JH Jr: Physiology of Respiration . Chicago, Year Book Medical Publishers Inc, 1974. 11. Berger AJ, Mitchell RA, Severinghaus JW: Regulation of respiration . N Engl J Med 1977;297:138-143.Crossref 12. Askanazi J, Silverberg PA, Foster RJ, Hyman AI, Milic-Emili J, Kinney JM: Effects of respiratory apparatus on breathing pattern . J Appl Physiol 1980;48:577-580. 13. Kinney JM: The application of indirect calorimetry in clinical studies, in Kinney JM (ed): Assessment of Energy Metabolism in Health and Disease, Report of the First Ross Conference on Medical Research. Columbus, Ohio, Ross Laboratories, 1980, pp 42-48. 14. Milic-Emili J, Grunstein MM: Drive and timing components of ventilation . Chest 1976;70( (suppl 1) ):131-133.Crossref 15. Askanazi J, Milic-Emili J, Broell JR, Hyman AI, Kinney JM: Influence of exercise and CO2 on breathing pattern of normal man . J Appl Physiol 1979;47:192-196. 16. Weissman C, Abraham B, Askanazi J, Milic-Emili J, Hyman AI, Kinney JM: Effect of posture on the ventilatory response to CO2 . J Appl Physiol 1982;53:761-765.Crossref 17. Padget P: The respiratory response to carbon dioxide . Am J Physiol 1927;83:384-394. 18. Liebowitz MR, Gorman JM, Fyer AJ, Levitt M, Dillon D, Levy G, Appleby I, Anderson S, Palij M, Davies SO, Klein DF: Lactate provocation of panic attacks: II. Biochemical and physiologic findings . Arch Gen Psychiatry 1985;42:709-719.Crossref 19. Grossman P, Deswart JGG: Diagnosis of hyperventilation syndrome on the basis of reported complaints . J Psychosom Res 1984;28:97-104.Crossref 20. Folgering H, Colla P: Some anomalies in the control of PACO2 in patients with a hyperventilation syndrome . Bull Eur Physiopathol Respir 1978;14:503-512. 21. Gorman JM, Fyer AJ, Ross DC, Cohen BS, Martinez J, Liebowitz MR, Klein DF: Normalization of venous pH, pCO2 and HCO3 levels after blockade of panic attacks . Psychiatry Res 1985;14:57-65.Crossref 22. Gorman JM, Liebowitz MR, Fyer AJ, Fyer MR, Klein DF: Possible respiratory abnormalities in panic disorder . Psychopharmacol Bull , in press. 23. Rapoport SI: Blood-Brain Barrier in Physiology and Medicine . New York, Raven Press, 1976. 24. Lum LC: Hyperventilation and anxiety states . J R Soc Med 1981;74:1-4. 25. Lum LC: Physiological considerations in the treatment of hyperventilation syndromes . J Drug Res 1983;8:1867-1872. 26. Clark DM, Salkovskis PM, Chalkly AJ: Respiratory control as a treatment for panic attacks . J Behav Ther Exp Psychiatry 1985;16:23-30.Crossref 27. Carr DB, Sheehan DV: Panic anxiety: A new biological model . J Clin Psychiatry 1984;45:323-330.

Woods, Scott W.;Charney, Dennis S.;Goodman, Wayne K.;Heninger, George R.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250051007pmid: 3122696

Abstract • Carbon dioxide was administered for 15 minutes to patients with panic disorders (5% CO2, n =14) and healthy subjects (5% CO2, n =11; 7.5% CO2, n = 8). Following administration of CO2 and air placebo, changes in behavioral ratings, vital signs, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol, cortisol, growth hormone, and prolactin were measured over three hours. In the healthy subjects, CO2 produced dose-related increases in anxiety, somatic symptoms, vital signs, and plasma cortisol levels. In the patients, the frequency of panic attacks (in eight of 14 patients) and the increases in anxiety and somatic symptoms induced by 5% CO2 exceeded those in the healthy subjects and were similar to those induced by 7.5% CO2 in the healthy subjects. The physiologic and biochemical measurements obtained did not elucidate the mechanisms underlying CO2-induced anxiety or the greater anxiogenic effects of CO2 seen in patients with panic disorders. 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Schalch DS, Packer ML: A sensitive double antibody immunoassay for human growth hormone in plasma . Nature 1964;263:1141-1142.Crossref 46. SAS Institute Inc: SAS User's Guide: Statistics. Cary, NC, SAS Institute Inc, 1982. 47. Dixon WJ, Brown MB, Engelman L, Frane JW, Hill MA, Jennvick RI, Toporek JD: BMDP Statistical Software: 1983 Printing With Additions . Berkeley, Calif, University of California Press, 1983. 48. Checkley SA, Glass IB, Thompson C, Corn T, Robinson P: The GH response to clonidine in endogenous as compared with reactive depression . Psychol Med 1984;14:773-777.Crossref 49. Berger AJ, Mitchell RA, Severinghaus JW: Regulation of respiration . N Engl J Med 1977;297:92-97, 138-143, 194-201.Crossref 50. Rebuck AS, Slutsky AS: Measurement of ventilatory responses to hypercapnia and hypoxia , in Hornbein TF (ed): Regulation of Breathing . New York, Marcel Dekker Inc, 1981, pp 745-772. 51. Dempsey JA: CO2 response: Stimulus definition and limitations . Chest 1976;70( (suppl) ):114-118.Crossref 52. Slater SL, Leavy A: The effects of inhaling a 35% CO2—65% O2 mixture upon anxiety level in neurotic patients . Behav Res Ther 1966;4:309-316.Crossref 53. Ley R, Walker H: Effects of carbon dioxide-oxygen inhalation on heart rate, blood pressure, and subjective anxiety . J Behav Ther Exp Psychiatry 1973;4:223-228.Crossref 54. Latimer P: Carbon dioxide as a reciprocal inhibitor in the treatment of neurosis . J Behav Ther Exp Psychiatry 1977;8:83-85.Crossref 55. Haslam MT: The relationship between the effect of lactate infusion on anxiety states, and their amelioration by carbon dioxide inhalation . Br J Psychiatry 1974;125:88-90.Crossref 56. Wolpe J: Psychotherapy by Reciprocal Inhibition . Stanford, Calif, Stanford University Press, 1985, pp 74, 166, 168. 57. Rose EC Jr, Althaus JA, Kaiser DL, Miller ED, Carey RM: Acute hypoxemia and hypercapnia: Increase in plasma catecholamines in conscious dogs . Am J Physiol 1983;245:H924-H929. 58. O'Brodovich HM, Stalcup SA, Pang LM, Mellins RB: Hemodynamic and vasoactive mediator response to experimental respiratory failure . J Appl Physiol 1982;52:1230-1236. 59. Miller RA, Morris ME: Norepinephrine release during respiratory acidosis in adrenalectomized dogs . Anesthesiology 1961;22:62-66.Crossref 60. Price HL, Lurie AA, Jones RE, Price ML, Linde HW: Cyclopropane anesthesia: II. Epinephrine and norepinephrine in initiation of ventricular arrhythmias by carbon dioxide inhalation . Anesthesiology 1958;19:619-630.Crossref 61. Charney DS, Heninger GR, Jatlow PI: Increased anxiogenic effects of caffeine in panic disorders . Arch Gen Psychiatry 1985;42:233-243.Crossref 62. Carr DB, Sheehan DV, Surman OS, Coleman JH, Greenblatt DJ, Heninger GR, Jones KJ, Levine PH, Watkins WD: Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy . Am J Psychiatry 1986;143:483-494. 63. 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Gaffney, F. Andrew;Fenton, Barry J.;Lane, Lynda D.;Lake, C. Ray

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250063008pmid: 3337609

Abstract • Hemodynamic, ventilatory, and biochemical variables were measured in ten healthy adults and ten panic patients during infusion of 0.5 mol/L of sodium lactate. Physical activity, fitness level, and ambulatory electrocardiograms were also recorded. Lactate infusion doubled cardiac output, increased blood lactate levels by sixfold, and produced hypernatremia, hypocalcemia, and decreased serum bicarbonate levels in both groups but raised arterial pressure only in the patients. The patients hyperventilated before and during the infusion. Physiological responses and somatic complaints with the infusion differed little between the groups, but emotional complaints were six times more frequent among the panic patients. Eight patients but no control subjects interpreted their symptoms as a panic attack. Heart rate increased with only 14 of 31 recorded spontaneous outpatient panic attacks. Sodium lactate infusions appear to produce panic by mimicking the physiology of spontaneous panic. Treatment with cardioactive agents is not indicated in the absence of cardiopulmonary or autonomic nervous system abnormalities. References 1. Jones M, Mellersh V: A comparison of the exercise response in anxiety states and normal controls . Psychosom Med 1946:8:180-187.Crossref 2. Linko E: Lactic acid response to muscular exercise in neurocirculatory asthenia . Ann Med Interne Fenniae 1950;39:161-176. 3. Holmgren A, Strom G: Blood lactate concentration and relative workload in normal men and in mitral stenosis, atrial septal defect, and vasoregulatory asthenia . Acta Med Scand 1959;163:183-184. 4. Pitts FN, McClure JN: Lactate metabolism in anxiety neurosis . N Engl J Med 1967;277:1329-1336.Crossref 5. Grosz HJ, Farmer BB: Pitts' and McClure's lactate-anxiety study revisited . Br J Psychiatry 1972;120:415-418.Crossref 6. Grosz HJ, Farmer BB: Blood lactate in the development of anxiety symptoms . Arch Gen Psychiatry 1969;21:611-619.Crossref 7. Kelly D, Mitchell-Heggs N, Sherman D: Anxiety and the effects of sodium lactate assessed clinically and physiologically . Br J Psychiatry 1971;119:129-141.Crossref 8. Bonn JA, Harrison J, Rees WL: Lactate infusion in the treatment of 'free-floating' anxiety . Can J Psychiatry 1973;18:41-46. 9. Gorman JM, Levy GF, Liebowitz MR. McGrath P, Appleby IL, Dillon DJ, Davies SO, Klein DF: Effect of acute β-adrenergic blockage on lactateinduced panic . Arch Gen Psychiatry 1983;40:1079-1082.Crossref 10. Freedman RR, Ianni P, Ettedgui E, Nandakumaran P: Ambulatory monitoring of panic disorder . Arch Gen Psychiatry 1985;42:244-248.Crossref 11. Spitzer RL, Williams JB: Structure Clinical Interview for DSM-III, Upjohn Version . New York, New York State Psychiatric Institute, 1983. 12. Gaffney FA, Karlsson ES, Campbell W, Schutte JE, Nixon JV, Willerson JT, Blomqvist CG: Autonomic dysfunction in women with mitral valve prolapse syndrome . Circulation 1979;59:894-901.Crossref 13. Triebwasser JH, Johnson RL, Burpo RP, Campbell JC, Reardon WC, Blomqvist CG: Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements . Aviat Space Environ Med 1977;48:203-209. 14. Nielsen MH, Nielsen NC: Spectrophotometric determination of Evans' blue dye in plasma with individual correction for blood density by a modified Gaebleis method . Scand J Clin Lab Invest 1962;14:605-617.Crossref 15. Durett LR, Ziegler MG: A sensitive radioenzymatic assay for catechol drugs . J Neurosci Res 1980;5:587-598.Crossref 16. Statistical Analysis System. Cary, NC, SAS Institute Inc, 1985. 17. Rubenstein E, Federman DD: Medicine . New York, Scientific American Inc, 1982, vol 6, pp 11-12. 18. Liebowitz MR, Fyer AJ, Gorman JM, Dillon D, Appleby IL, Levy G, Anderson S, Levitt M, Palij M, Davies SO, Klein DF: Lactate provocation of panic attacks: I. Clinical and behavioral findings . Arch Gen Psychiatry 1984;41:764-770.Crossref 19. Liebowitz MR, Gorman JM, Fyer AJ, Levitt M, Dillon D, Levy G, Appleby IL, Anderson S, Palij M, Davies SO, Klein DF: Lactate provocation of panic attacks: II. Biochemical and physiological findings . Arch Gen Psychiatry 1985;42:709-719.Crossref 20. Shear MK, Polan JJ, Harshfield G, Pickering T, Mann JJ, Frances A, James G: Ambulatory monitoring of blood pressure and heart rate in panic patients, abstracted. Philadelphia, Society for Behavioral Medicine, 1984. 21. Taylor CB, Sheikh J, Agras WS, Roth WT, Margraf J, Ehlers A, Maddock RJ, Gossand D: Ambulatory heart rate changes in patients with panic attacks . Am J Psychiatry 1986;143:478-482. 22. Charney DS, Heninger GR, Breier A: Noradrenergic function in panic anxiety . Arch Gen Psychiatry 1984;41:751-763.Crossref 23. Boulenger JP, Uhde TW, Wolff EA III, Post RM: Increased sensitivity to caffeine in patients with panic disorders . Arch Gen Psychiatry 1984;41:1067-1071.Crossref 24. Charney DS, Heninger GR, Jatlow PI: Increased anxiogenic effects of caffeine in panic disorders . Arch Gen Psychiatry 1985;42:233-243.Crossref 25. Folkow B, Neil E: Circulation . New York, Oxford University Press Inc, 1971, pp 340-363. 26. Nesse RM, Cameron OG, Curtis GC, McCann DS, Huber-Smith MJ: Adrenergic function in patients with panic anxiety . Arch Gen Psychiatry 1984;41:771-776.Crossref 27. Carr DB, Sheehan DV: Panic anxiety: A new biological model . J Clin Psychiatry 1984;45:323-330. 28. Neill WA, Hattenhauer M: Impairment of myocardial O2 supply due to hyperventilation . Circulation 1975;52:854-858.Crossref 29. Mudge GH Jr, Goldberg S, Gunther S, Mann T, Grossman W: Comparison of metabolic and vasoconstrictor stimuli on coronary vascular resistance in man . Circulation 1979;59:544-552.Crossref 30. Folkow B, Neil E: Circulation . New York, Oxford University Press Inc, 1971, pp 440-443. 31. Gorman JM, Askanazi J, Liebowitz MR, Fyer AJ, Stein J, Kinney JM, Klein DF: Response to hyperventilation in a group of patients with panic disorder . Am J Psychiatry 1984;141:857-861. 32. Gorman JM, Cohen BS, Liebowitz MR, Fyer AJ, Ross D, Davies SO, Klein DF: Blood gas changes and hypophosphatemia in lactate-induced panic . Arch Gen Psychiatry 1986;43:1067-1071.Crossref 33. Cross SA, Calloway CW: D-lactic acidosis and selected cerebellar ataxias . Mayo Clin Proc 1984;59:202-205.Crossref 34. Dahlquist NR, Perrault J, Calloway CW, Jones J: D-lactic acidosis and encephalopathy after jejuno-ileostomy-ileostomy: Response to overfeeding and to fasting in humans . Mayo Clin Proc 1984;59:141-145.Crossref 35. Morbert CL: Lactate dehydrogenase: Biochemistry and function of lactate dehydrogenase . Cell Biochem Funct 1984;2:131-134.Crossref 36. Holmgren A, Strom G: Blood lactate concentration in relation to absolute and relative workload in normal men and in mitral stenosis, atrial septal defect, and vasoregulatory asthenia . Acta Med Scand 1959;163:185-193.Crossref 37. Frohlich ED, Dustan HP, Tarazi RC: Hyperdynamic β-adrenergic circulatory state: An overview . Arch Intern Med 1970;126:1068-1069.Crossref 38. Easton JD, Sherman DG: Somatic anxiety attacks and propranolol . Arch Neurol 1976;33:689-691.Crossref

Paulsen, Annamarie Spillane;Crowe, Raymond R.;Noyes, Russell;Pfohl, Bruce

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250076009pmid: 3337610

Abstract • The reliability of psychiatric diagnosis using the Schedule of Affective Disorders and Schizophrenia—Lifetime Version in personal and telephone Interviews with 39 subjects was assessed using a 12- to 19-month test-retest design. Interrater reliability was high (K,.69 to.84) for the diagnosis of panic disorder, agoraphobia with panic attacks, probable panic disorder, major depression, and alcohol abuse. We conclude that it is possible to reliably make these lifetime diagnoses in a family study using the telephone interview. References 1. Aneshensel CS, Frerichs RR, Clark VA, Yokopenic PA: Measuring depression in the community: A comparison of telephone and personal interviews . Public Opinion Q 1982;46:110-121.Crossref 2. American Psychiatric Association, Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders , ed 3. Washington, DC, American Psychiatric Association, 1980. 3. Robins LN, Helzer JE, Croughan J, Ratcliff KS: National Institute of Mental Health Diagnostic Interview Schedule: Its history, characteristics, and validity . Arch Gen Psychiatry 1981;38:381-389.Crossref 4. Katon W: DIS screening for panic disorder in medical populations . DIS Newslett 1986;3:3-5. 5. DiNardo PA, O'Brien GT, Barlow DH, Waddell MT, Blanchard EB: Reliability of DSM-III anxiety disorder categories using a new structured interview . Arch Gen Psychiatry 1983;40:1070-1074.Crossref 6. Grove WM, Andreasen NC, McDonald-Scott P, Keller MB, Shapiro RW: Reliability studies of psychiatric diagnosis: Theory and practice . Arch Gen Psychiatry 1981;38:408-413.Crossref 7. Andreasen NC, Grove WM, Shapiro RW, Keller MB, Hirschfeld RMA, McDonald-Scott P: Reliability of lifetime diagnosis: A multicenter collaborative perspective . Arch Gen Psychiatry 1981;38:400-405.Crossref 8. Crowe RR, Noyes R, Pauls DL, Slymen D: A family study of panic disorder . Arch Gen Psychiatry 1983;40:1065-1069.Crossref 9. Crowe RR, Noyes R: Panic disorder and agoraphobia . Disease-A-Month 1986;7:390-444.

Popkin, Michael K.;Callies, Allan L.;Lentz, Richard D.;Colon, Eduardo A.;Sutherland, David E.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250078010pmid: 3257379

Abstract • To examine the prevalence of psychiatric disorders in patients with long-standing type I diabetes mellitus, we assessed a series of candidates for pancreas transplantation. Using the Diagnostic Interview Schedule, six-month and lifetime prevalences of psychiatric disorders were established for the candidates and their potential donors (first-degree relatives). Excluding tobacco use disorder and psychosexual dysfunction, 38 diabetic subjects (51%) received one or more psychiatric diagnoses. The lifetime prevalence of major depression was comparable for female (11 of 48 [22.9%]) and male (seven of 27 [25.9%]) diabetics; both rates were significantly higher than rates in first-degree relatives and the general population. Among female diabetics, the six-month and lifetime prevalences of simple phobia were increased vs donors and the general population; among male diabetics, the lifetime prevalence of antisocial personality disorder was greater than that in the general population. None of these disorders was found to be related to the duration of diabetes or the presence of various complications. The data suggest that increased rates of psychiatric disorder in type I diabetics have both gender-independent and gender-related components. References 1. Ryan C, Vega A, Drash A, Longstreet C: Neuropsychological changes in adolescents with insulin-dependent diabetes . J Consult Clin Psychol 1984;52:335-342.Crossref 2. Ryan C, Vega A, Drash A: Cognitive deficits in adolescents who developed diabetes early in life . Pediatrics 1985;75:921-927. 3. Perlmuter LC, Hakami MK, Hodgson-Harrington C, Ginsberg J, Katz J, Singer DE, Nathan DM: Decreased cognitive function in aging non—insulin dependent diabetic patients . Am J Med 1984;77:1043-1048.Crossref 4. Lustman PJ, Amado H, Wetzel RD: Depression in diabetes: A critical appraisal . Compr Psychiatry 1983;1:65-74.Crossref 5. Robins LN, Helzer JE, Croughan J, Rutcliff KS: NIMH Diagnostic Interview Schedule: Its history, characteristics, validity . Arch Gen Psychiatry 1981;38:381-389.Crossref 6. Lustman PJ, Harper GW, Griffith LS, Clouse RE: Use of the Diagnostic Interview Schedule in patients with diabetes mellitus . J Nerv Ment Dis 1986;174:743-746.Crossref 7. Lustman PJ, Griffith LS, Clouse ER, Cryer PE: Psychiatric illness in diabetes mellitus: Relationship to symptoms and glucose control . J Nerv Ment Dis 1986;174:736-742.Crossref 8. Popkin MK, Callies AL: Psychiatric consultation to inpatients with early onset type I diabetes mellitus in a university hospital . Arch Gen Psychiatry 1987;44:169-171.Crossref 9. Sutherland DER, Kendall DM: Pancreas transplantation: Registry Report and a commentary . West J Med 1985;143:845-852. 10. Sutherland DER, Goetz FC, Kendall DM, Najarian JS: One institution's experience with pancreas transplantation . West J Med 1985;143:838-844. 11. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Regier DA: Lifetime prevalence of specific psychiatric disorders in three sites . Arch Gen Psychiatry 1984;41:949-958.Crossref 12. Myers JK, Weissman MM, Tischler GL, Holzer CE, Leaf PJ, Orvaschel H, Anthony JC, Boyd JH, Burke JD, Kramer H, Stoltzman R: Sixmonth prevalence of psychiatric disorders in three communities . Arch Gen Psychiatry 1984;41:959-967.Crossref 13. Robinson RG, Lipsey JR: Cerebral localization of emotion based on clinical-neuropathological correlations: Methodological issues . Psychiatr Dev 1985;4:335-347. 14. Robinson RG, Kubos KL, Starr LB, Rao K, Price TR: Mood disorders in stroke patients: Importance of location and lesion . Brain 1984;107:81-93.Crossref 15. Hoeper E, Nycz G, Cleary P, Regier D, Goldberg I: Estimated prevalence of RDC mental disorder in primary medical care . Int J Ment Health 1979;8:6-15. 16. Helzer JE, Chammas S, Norland CC, Stillings WA, Alpers DH: A study of the association between Crohn's disease and psychiatric illness . Gastroenterology 1984;86:324-330. 17. Leeper J, Badger L, Milo T: Mental disorders among physical disability determination patients . Am J Public Health 1985;75:78-79.Crossref 18. Schulberg HC, Saul M, McClelland M, Ganguli M, Christy W, Frank R: Assessing depression in primary medical and psychiatric practices . Arch Gen Psychiatry 1985;42:1164-1170.Crossref 19. Popkin MK, Callies AL, Colon E: A framework for the study of medical depression . Psychosomatics 1987;28:27-33.Crossref 20. Keller MB, Klerman GL, Lavori PW, Fawcett JA, Coryell W, Endicott J: Treatment received by depressed patients . JAMA 1982;248:1848-1855.Crossref 21. Lustman PJ, Harper GW: Nonpsychiatric physicians' identification and treatment of depression in patients with diabetes . Compr Psychiatry 1987;28:22-27.Crossref 22. Normand PS, Jenike MA: Lowered insulin requirements after ECT . Psychosomatics 1984;25:418-419.Crossref 23. Kronfol Z, Greden J, Farroll B: Psychiatric aspects of diabetes mellitus: Diabetes and depression . Br J Psychiatry 1981;139:172. 24. Alex M, Baron EK, Goldenberg S, Blumenthal HT: An autopsy study of cerebrovascular accident in diabetes mellitus . Circulation 1962;25:663-673.Crossref 25. Kannell WB, McGee DL: Diabetes and cardiovascular disease: The Framingham Study . JAMA 1979;241:2035-2038.Crossref 26. Roth M: The natural history of mental disorder in old age . J Ment Sci 1955;101:281-301. 27. Post F: Significance of Affective Symptoms in Old Age: A Follow-up Study of 100 Patients , Maudsley Monograph No. 10. New York, Oxford University Press Inc, 1962. 28. Clayton PJ, Lewis CE: The significance of secondary depression . J Affective Disord 1981;3:25-35.Crossref 29. Mavissakalian M, Barlow DH: Phobia: Psychological and Pharmacological Treatment . New York, Guilford Press, 1981, pp 1-34. 30. Sheehan DV, Sheehan KH: The classification of anxiety and hysterical states: II. Toward a more heuristic classification . J Clin Psychopharmacol 1982;2:386-393. 31. Mackenzie TB, Popkin MK: Organic anxiety syndrome . Am J Psychiatry 1983;140:342-344. 32. Auer RN: Progress review: Hypoglycemic brain damage . Stroke 1986;17:699-708.Crossref 33. Pinart J: Diabetes mellitus and its complications: A prospective study of 4400 patients observed between 1947 and 1973 . Diabetes Care 1978;1:168-188.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250082011

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract Incorrect Figure.— In the letter to the editor by Breier et al entitled "Metabolic Stress Produces Rapid Immunosuppression in Humans," which appeared in the December 1987 issue of the Archives (1987;44:1108-1109), an error occurred in the Figure. The infusion labels in the upper right and lower left portions of the graph were transposed, ie, both infusions in the 2-DG column should have been 2-DG and both infusions in the placebo column should have been placebo. A corrected figure appears to the right. The Archives regrets this error.Effects of 2-deoxy-d-glucose (2-DG)-induced stress on mitogen T-cell proliferation. Each value represents a mean of six wells. Each subject is represented by the same numeral (N = 4). Con-A indicates concanavalin A; PHA, phytohemagglutinin; and cpm, counts per minute. Baseline After 2-DG Infusion After Placebo Infusion PHA, 2.5 μg/Well Baseline After 2-DG Infusion Baseline After Placebo Infusion

Farde, Lars;Wiesel, Fritz-Axel;Halldin, Christer;Sedvall, Göran

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250087012pmid: 2892477

Abstract • Using positron emission tomography and the carbon 11—labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11—raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline. References 1. Delay J, Deniker O: Caracteristiques psycho-physioloques des medicaments neuroleptiques , in Garattini S, Ghetti V (eds): The Psychotropic Drugs . Amsterdam, Elsevier Science Publishers, 1957, pp 485-501. 2. Klein D, Davis J: Diagnosis and Drug Treatment of Psychiatric Disorders . Baltimore, Williams & Wilkins, 1962. 3. Wiesel F-A, Alfredsson G, Likwornik V, Sedvall G: A relation between drug concentrations in brain and striatal homovanillic acid levels in chlorpromazine treated rats . Life Sci 1975;16:1145-1156.Crossref 4. Dahl S: Plasma level monitoring of antipsychotic drugs: Clinical utility . Clin Pharmacokinet 1986;11:36-61.Crossref 5. Carlsson A, Lindqvist M: Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain . Acta Pharmacol Toxicol 1963;20:140-144.Crossref 6. Carlsson A: Antipsychotic drugs, neurotransmitters, and schizophrenia . Am J Psychiatry 1978;135:164-173. 7. Creese I, Burt DR, Snyder SH: Dopamine receptor binding clinical and pharmacological potencies of antischizophrenic drugs . Science 1976;192:481-483.Crossref 8. Seeman P, Lee T, Chau-Wong M, Wong K: Antipsychotic drug doses and neuroleptic/dopamine receptors . Nature 1976;261:717-719.Crossref 9. 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Baldessarini, Ross J.;Cohen, Bruce M.;Teicher, Martin H.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250095013pmid: 2892478

Abstract • The clinical use of antipsychotic agents may be enhanced by considering their dose-effect characteristics. In particular, assessment of immediate and later follow-up treatment of psychotic patients (1) indicates that moderate doses are adequate for most patients, (2) fails to support the utility of unusually high doses, and (3) even suggests the existence of a biphasic relationship of antipsychotic efficacy to dose of neuroleptics and possibly to plasma concentrations of the drugs as well. Trends toward lesser overall clinical benefits of high doses may reflect untoward extrapyramidal or other central nervous system effects leading to behavioral and cognitive symptoms. Thus, moderate doses of neuroleptics appear, on average, to be about as effective as, and probably safer than, the larger doses that have been popular in the United State in recent years. References 1. References 78,101, 102, 104-108,114, 116-118. 2. References 105-107, 111, 112,115, 117-120. 3. 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Blackburn HL, Allen JL: Behavioral effects in interrupting and resuming tranquilizing medication among schizophrenics . J Nerv Ment Dis 1961;133:303-308.Crossref 134. Schiele BC, Vestre ND, Stein KE: A comparison of thioridazine, trifluoperazine, chlorpromazine, and placebo: A double-blind controlled study on the treatment of chronic hospitalized, schizophrenic patients . J Clin Exp Psychopathol 1961;22:151-162. 135. Freeman LS, Alson E: Prolonged withdrawal of chlorpromazine in chronic patients . Dis Nerv Syst 1962;23:522-525. 136. Troshinsky CH, Aaronson HG, Stone RK: Maintenance phenothiazines in aftercare of schizophrenic patients . Penn Psychiatr Q 1962;2:11-15. 137. Whitaker CB, Hoy RM: Withdrawal of perphenazine in chronic schizophrenia . Br J Psychiatry 1963;109:422-427.Crossref 138. Caffey EM, Diamond LS, Frank TV, Grasberger JC, Herman L, Klett CJ, Rothstein C: Discontinuation or reduction of chemotherapy in chronic schizophrenics . J Chronic Dis 1964;17:347-358.Crossref 139. Pasamanick B, Scarpitti FR, Lefton M, Dinitz S, Wernet JJ, McPheeters H: Home vs. hospital care for schizophrenics . JAMA 1964;187:177-181.Crossref 140. Kinross-Wright J, Charalampous KD: A controlled study of a very long-acting phenothiazine preparation . Int J Neuropsychiatry 1965;1:66-70. 141. Garfield SL, Gershon S, Sletten I, Neubauer H, Ferrel E: Withdrawal of ataractic medication in schizophrenic patients . Dis Nerv Syst 1966;27:321-325. 142. Melnyk WT, Worthington AG, Laverty SG: Abrupt withdrawal of chlorpromazine and thioridazine from schizophrenic inpatients . Can Psychiatr Assoc J 1966;11:410-413. 143. Englehardt DM, Rosen B, Freedman N, Margolis R: Phenothiazines in prevention of psychiatric hospitalization . Arch Gen Psychiatry 1967;16:98-101.Crossref 144. Prien RF, Cole JO: High dose chlorpromazine therapy in chronic schizophrenia . Arch Gen Psychiatry 1968;18:482-495.Crossref 145. Prien RF, Cole JO, Belkin NF: Relapse in chronic schizophrenics following abrupt withdrawal of tranquilizing drugs . Br J Psychiatry 1969;115:679-686.Crossref 146. Prien RF, Levine J, Cole JO: High dose trifluoperazine therapy in chronic schizophrenia . Am J Psychiatry 1969;126:305-313. 147. Itil T, Keskiner A: Fluphenazine hydrochloride, enanthate, and decanoate in the management of chronic psychosis . Dis Nerv Syst 1970;31 ( (suppl) ):37-42. 148. Leff JP, Wing JK: Trial of maintenance therapy in schizophrenics . Br Med J 1971;3:599-604.Crossref 149. Hershon HI, Kennedy PF, McGuire RJ: Persistence of extrapyramidal disorders and psychiatric relapse after withdrawal of long-term phenothiazine therapy . Br J Psychiatry 1972;120:41-50.Crossref 150. Hirsch SR, Gaind R, Rohde PD, Stevens BC, Wing JK: Outpatient maintenance of chronic schizophrenic patients with long-acting fluphenazine: Double-blind placebo trial . Br Med J 1973;1:633-637.Crossref 151. Hogarty GE, Goldberg SC, Collaborative Study Group: Drugs and sociotherapy in the aftercare of schizophrenic patients: One-year relapse rates . Arch Gen Psychiatry 1973;30:54-64.Crossref 152. Hogarty GE, Goldberg SC, Schooler NR, Ulrich RF: Drugs and sociotherapy in the aftercare of schizophrenic patients: II. Two-year relapse rates . Arch Gen Psychiatry 1974;31:603-608.Crossref 153. Hogarty GE, Ulrich RF, Mussare F, Aristigueta N: Drug discontinuation among long-term successfully maintained schizophrenic outpatients . Dis Nerv Syst 1976;37:494-500. 154. Hogarty GE, Ulrich RF: Temporal effects of drug and placebo in delaying relapse in schizophrenic outpatients . Arch Gen Psychiatry 1977;34:297-301.Crossref 155. Hogarty GE, Schooler NR, Ulrich RF, Mussare F, Ferro P, Herron E: Fluphenazine and social therapy in the aftercare of schizophrenic patients . Arch Gen Psychiatry 1979;36:1283-1294.Crossref 156. Gross HL: A double-blind comparison of once-a-day pimozide, trifluoperazine and placebo in the maintenance care of chronic schizophrenic outpatients . Curr Ther Res 1974;16:696-705. 157. Chien C-P: Drugs and rehabilitation in schizophrenia , in Greenblatt M (ed): Drugs in Combination With Other Therapies . New York, Grune & Stratton, 1975, pp 13-34. 158. Clark ML, Huber W, Hill D, Wood F, Costiloe JP: Pimozide (and thioridazine) in chronic outpatients . Dis Nerv Syst 1975;36:137-141. 159. Andrews P, Hall JN, Snaith RP: A controlled trial of phenothiazine withdrawal in chronic schizophrenic patients . Br J Psychiatry 1976;128:451-455.Crossref 160. Johnson DAW: The duration of maintenance therapy in chronic schizophrenia . Acta Psychiatr Scand 1976;53:298-301.Crossref 161. Rifkin A, Quitkin F, Robiner DJ, Klein DF: Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics: I. Relapse rates after one year . Arch Gen Psychiatry 1977;34:43-47.Crossref 162. Quitkin F, Rifkin A, Kane J, Ramos-Lorenzi JR, Klein DF: Longacting oral vs. injectable antipsychotic drugs in schizophrenics: A one-year double-blind comparison in multiple episode schizophrenics . Arch Gen Psychiatry 1978;35:889-892.Crossref 163. Levine J, Schooler NR, Severe J, Escobar J, Gelenberg A, Mandel M, Sovner R, Steinbook R: Discontinuation of oral and depot fluphenazine in schizophrenic patients after one year of continuous medication: A controlled study . Adv Biochem Psychopharmacol 1980;24:483-493. 164. Muller P, Kind J: A study on the prophylaxis of relapse. Reported by Hartmann W, Kind J, Meyer JE, Muller P, Steuber H: Neuroleptic drugs and the prevention of relapse in schizophrenia: A workshop report . Schizophr Bull 1980;6:536-541.Crossref 165. Branchey MH, Branchey LB, Richardson MA: Effects of neuroleptic adjustment on clinical condition and tardive dyskinesia in schizophrenic patients . Am J Psychiatry 1981;138:608-612. 166. Cheung HK: Schizophrenics fully remitted on neuroleptics for threefive years: To stop or continue drugs? Br J Psychiatry 1981;138:490-494.Crossref 167. Wistedt B: A depot neuroleptic withdrawal study: A controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients . Acta Psychiatr Scand 1981;64:65-84.Crossref 168. Kane JM, Rifkin A, Quitkin F, Nayak D, Ramos-Lorenzi J: Fluphenazine vs. placebo in patients with remitted, acute first-episode schizophrenia . Arch Gen Psychiatry 1982;39:70-73.Crossref 169. Johnson DAW, Pasterski G, Ludlow JM, Street K, Taylor RDW: The discontinuance of maintenance neuroleptic therapy in chronic schizophrenic patients: Drug and social consequences . Acta Psychiatr Scand 1983;67:339-352.Crossref 170. Nishikawa T, Tsuda A, Tanaka M, Koga I, Uchida Y: Prophylactic effects of neuroleptics in symptom-free schizophrenics: Roles of dopaminergic and noradrenergic blockers . Biol Psychiatry 1985;20:1161-1166.Crossref 171. Chouinard G, Jones BB, Annable L: Neuroleptic-induced supersensitivity psychosis . Am J Psychiatry 1978;135:1409-1410. 172. Gurland BJ, Fleiss JL, Cooper JE, Sharpe L, Kendall RE, Roberts P: Cross-national study of diagnosis of mental disorders: Hospital diagnoses and hospital patients in New York and London . Compr Psychiatry 1970;11:18-25.Crossref 173. Kane JM, Smith JM: Tardive dyskinesia: Prevalence and risk factors, 1959 to 1979 . Arch Gen Psychiatry 1982;39:473-481.Crossref 174. Quitkin F, Rifkin A, Klein DF: Very high dosage vs. standard dosage fluphenazine in schizophrenia . Arch Gen Psychiatry 1975;32:1276-1281.Crossref 175. Schiele B, Mendelsohn RM, Penman AS, Schofield W: Comparison of low and high dosage procedures in chlorpromazine therapy . Psychiatr Q 1959;33:252-259.Crossref 176. Carscallen HB, Rochman H, Lovegrove TD: High dosage trifluoperazine in schizophrenia . Can Psychiatr Assoc J 1968;13:459-461. 177. Polvan N, Vagcioglu V, Itil T, Fink M: High and very high dose fluphenazine in the treatment of chronic psychosis, in Proceedings of the Sixth International Congress of Neuropsychopharmacology. Princeton, NJ, Excerpta Medica, 1968, International Congress Series No. 180, pp 495-497. 178. Simpson GM, Amin M, Kurz-Bartholini E, Watts PTS, Laska E: Problems in the evaluation of the optimal dose of a phenothiazine (butaperazine) . Dis Nerv Syst 1968;29:478-484. 179. Brotman RK, Muzekari LH, Shanken PM: Butaperazine in chronic schizophrenic patients: A double-blind study . Curr Ther Res 1969;11:5-8. 180. Williams JR, Solecki RT, Puttkammer S: Effects of single, combined and non-drug treatments of chronic mental patients . Dis Nerv Syst 1969;30:696-701. 181. Clark ML, Ramsey HR, Ragland RE, Rahdal DK, Serafetinides EA, Costiloe JP: Chlorpromazine in chronic schizophrenia: Behavioral doseresponse relationships . Psychopharmacologia 1970;18:260-270.Crossref 182. Faleni RA: The use of high doses of fluphenazine in the treatment of psychotic patients . Psychosomatics 1970;11:496-499.Crossref 183. Itil T, Keskiner A, Heinemann L, Han T, Gannon P, Hsu W: Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride . Psychosomatics 1970;11:456-463.Crossref 184. Itil T, Saletu B, Hsu W, Kiremitci N, Keskiner A: Clinical and quantitative EEG changes at different dosage levels of fluphenazine treatment . Acta Psychiatr Scand 1971;47:440-451.Crossref 185. DeBuck RP: Relative safety and efficacy of high and low dose administration of fluphenazine HCI to psychotic patients, in Proceedings of the Eighth International Congress of Neuropsychopharmacology. Princeton, NJ, Excerpta Medica, 1972, International Congress Series No. 184, pp 265-272. 186. Clark ML, Ramsey HR, Rahdal DK, Serafetinides EA, Wood FD, Costiloe JP: Chlorpromazine in chronic schizophrenia: The effect of age and hospitalization on behavioral dose response relationships . Arch Gen Psychiatry 1972;27:479-483.Crossref 187. Gardos G, Orzack M, Finn G, Cole JO: High and low-dose thiothixene treatment of chronic schizophrenia . Dis Nerv Syst 1974;35:53-58. 188. McClelland HA, Farquharson RG, Leyburn P, Furness JA, Schiff AA: Very high dose fluphenazine decanoate: A controlled trial in chronic schizophrenia . Arch Gen Psychiatry 1976;33:1435-1439.Crossref 189. McCreadie RG, Macdonald IM: High dosage haloperidol in chronic schizophrenia . Br J Psychiatry 1977;131:310-316.Crossref 190. Deneker SJ, Johansson R, Lundin L, Malm U: High doses of fluphenazine enanthate in schizophrenia: A controlled study . Acta Psychiatr Scand 1978;57:405-414.Crossref 191. Goldstein MJ, Rodnick EH, Evans JR, May PRA, Steinberg MR: Drug and family therapy in the aftercare of acute schizophrenics . Arch Gen Psychiatry 1978;35:1169-1177.Crossref 192. McCreadie RG, Flanagan WL, McKnight J, Jorgensen A: High dose flupenthixol decanoate in chronic schizophrenia . Br J Psychiatry 1979;135:175-179.Crossref 193. Bjørndal N, Bjerre M, Gerlach J, Kristjansen P, Magelund G, Oestrich IH, Waehrens J: High dosage haloperidol therapy in chronic schizophrenic patients: A double-blind study of clinical response, sideeffects, serum haloperidol, and serum prolactin . Psychopharmacology 1980;67:17-23.Crossref 194. Carpenter WT, Stevens JH, Rey AC, Hanlon TE, Heinrichs DW: Early intervention vs. continuous pharmacotherapy in schizophrenia . Psychopharmacol Bull 1982;18:21-23. 195. Kane JM: Antipsychotic drug side effects: Their relationship to dose . J Clin Psychiatry 1985;46:16-21. 196. Hogarty GE: Depot neuroleptics: The relevance of psychosocial factors: A United States perspective . J Clin Psychiatry 1984;45:36-42. 197. Nishikawa T, Tsuda A, Tanaka M, Hoaki Y, Koga I, Uchida Y: Prophylactic effect of neuroleptics in symptom-free schizophrenics: A comparative dose-response study of haloperidol and propericiazine . Psychopharmacology 1984;82:153-156.Crossref 198. Herz MI, Szymanski HV, Simon JC: Intermittent medication for stable schizophrenic outpatients: An alternative to maintenance medication . Am J Psychiatry 1982;139:918-922. 199. Packer R, Waud D: Pharmacological estimation of drug-receptor dissociation constants . J Pharmacol Exp Ther 1971;177:1-12. 200. Nedler JA, Mead R: A simplex method for function minimization . Comput J 1965;7:308-313.Crossref 201. Van Putten T: The clinical management of noncompliance , in Barovsky I, Budson RD (eds): The Chronic Psychiatric Patient in the Community: Principles of Treatment . Jamaica, NY, Spectrum Publications Inc, 1983, pp 383-395. 202. Hartmann W, Kind J, Meyer JE, Muller P, Steuber H: Neuroleptic drugs and the prevention of relapse in schizophrenia: A workshop report . Schizophr Bull 1980;6:536-541.Crossref 203. Gardos G, Samu I, Kallos M, Cole JO: Absence of severe tardive dyskinesia in Hungarian schizophrenic outpatients . Psychopharmacology 1980;71:29-34.Crossref 204. Doongaji DR, Jeste DV, Jape NM, Sheth AS, Apte JS, Vahia VN, Desai AB, Vahora SA, Thatte S, Vevaina T, Bharadwaj J: Tardive dyskinesia in India . J Clin Psychopharmacol 1982;2:341-344.Crossref

Bass, Christopher;Gardner, W. N.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250111014pmid: 3122697

Abstract To the Editor.— Gorman et al1 urge that further work be aimed at defining the nature of ventilatory abnormalities in patients with panic disorder (PD) but do not elaborate on the substantial body of work that has already been published in this field. The important association between agoraphobia and hyperventilation (HV)-related complaints has already been established in different populations,2,3 and we have shown that some patients with agoraphobia and PD spend large portions of the waking day in the hypocapnic range (carbon dioxide partial pressure [Pco2], <30 mm Hg).4,5 For those patients at or close to the threshold for hypocapnia, relatively minor stressors, such as exercise, talking, or even exposure to phobic talk,6 may provoke sudden reductions in Pco2 that are accompanied by somatic symptoms and panic anxiety. Rapee7 also demonstrated that patients with PD had not only lower resting end-tidal Pco2 and References 1. Gorman JM, Cohen BS, Liebowitz MR, Fyer AJ, Ross D, Davies SO, Klein DF: Blood gas changes and hypophosphatemia in lactate-induced panic . Arch Gen Psychiatry 1986;43:1067-1071.Crossref 2. Garssen B, Van Veenendaal W, Bloemink R: Agoraphobia and the hyperventilation syndrome . Behav Res Ther 1983;21:643-649.Crossref 3. Bass C, Cawley RH, Wade C, Ryan KC, Gardner WN, Hutchison DCS, Jackson G: Unexplained breathlessness and psychiatric morbidity in patients with normal and abnormal coronary arteries . Lancet 1983;1:605-609.Crossref 4. Bass C, Gardner WN: Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation . Br Med J 1985;290:1387-1390.Crossref 5. Gardner WN, Meah MS, Bass C: Controlled study of respiratory responses during prolonged measurement in patients with chronic hyperventilation . Lancet 1986;2:826-830.Crossref 6. Freeman LJ, Conway AV, Nixon PGF: Physiological responses to psychological challenge under hypnosis in patients considered to have the hyperventilation syndrome: Implications for diagnosis and therapy . J R Soc Med 1986;79:76-83. 7. Rapee R: Differential response to hyperventilation in panic disorder and generalized anxiety disorder . J Abnorm Psychol 1986;95:24-28.Crossref 8. Ackerman S, Sachar E: The lactate theory of anxiety: A review of re-evaluation . Psychosom Med 1974;36:69-81.Crossref 9. Margraf J, Ehlers A, Roth WT: Biological models of panic disorder and agoraphobia: A review . Behav Res Ther 1986;24:553-567.Crossref 10. Hibbert GA: The diagnosis of hyperventilation using ambulatory carbon dioxide monitoring. Read before the Fourth International Symposium on Respiratory Psychophysiology, Southampton, England, 1984. 11. Salkovskis PM, Jones DR, Clark DM: Respiratory control in the treatment of panic attacks: Replication and extension with concurrent measurement of behaviour and CO2 . Br J Psychiatry 1986;148:526-532.Crossref 12. King R, Margraf J, Ehlers A, Maddock RJ: Panic disorder: Overlap with symptoms of somatization disorder , in Hand I, Wittchen HU (eds): Panic and Phobias . New York, Springer Publishing Co Inc, 1986. 13. Smith GR, Monson RA, Ray DC: Patients with multiple unexplained symptoms . Arch Intern Med 1986;146:69-72.Crossref

Dilsaver, Steven C.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250112017pmid: 3337611

Abstract To the Editor.— Recent reports strongly suggest that lithium potentiates the efficacy of tricyclic antidepressants (TCAs).1-4 Investigators have proposed that this is due to lithium's activation of a presynaptic serotoninergic mechanism.2,4 This may indeed be a factor. However, other factors may also be contributory.Long-term treatment with TCAs produces dose-dependent supersensitivity of central muscarinic mechanisms.5,6 Hyperfunction of central muscarinic mechanisms may be involved in the pathophysiology of melancholia.7-10 Cohen and Baldessarini11 reported that some patients developed tolerance to the antidepressant effects of TCAs. Snider and I6 have suggested that the capacity of TCAs to supersensitize muscarinic mechanisms may exacerbate the pathophysiologic defect underlying melancholia. Materials and Methods.— We recently found that lithium chloride (160 mg/kg intraperitoneally at 9 AM and 5 PM) blocks the capacity of amitriptyline (10 mg/kg intraperitoneally at 9 AM and 5 PM) to sensitize a muscarinic mechanism in adult References 1. De Montigny C, Cournoyer G, Morissette R, Langlois R, Caillé G: Lithium carbonate addition in tricyclic antidepressant—resistant unipolar depression: Correlations with the neurobiologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system . Arch Gen Psychiatry 1983;40:1327-1334.Crossref 2. Heninger GR, Charney DS, Sternberg DE: Lithium carbonate augmentation of antidepressant treatment: An effective prescription for treatment of refractory depression . Arch Gen Psychiatry 1983;40:1335-1342.Crossref 3. Price LH, Charney DS, Heninger GR: Manic symptoms following addition of lithium to antidepressant treatment . J Clin Psychopharmacol 1984;6:361-362.Crossref 4. Charney DS, Heninger GR, Sternberg DE: Serotonin functions and mechanism of action of antidepressant treatment: Effects of amitriptyline and desipramine . Arch Gen Psychiatry 1984;41:359-365.Crossref 5. Dilsaver SC, Snider RM, Alessi NE: Amitriptyline supersensitizes a central cholinergic mechanism . Biol Psychiatry 1987;22:495-507.Crossref 6. Dilsaver SC, Snider RM: Amitriptyline produces dose-dependent supersensitivity of a central cholinergic mechanism . J Clin Psychopharmacol , in press. 7. Janowsky DS, El-Yousef MK, Davis JM, Sekenkey HJ: A cholinergic adrenergic hypothesis of depression and mania . Lancet 1972;2:632-635.Crossref 8. Dilsaver SC: Pharmacologic induction of cholinergic system up-regulation and supersensitivity in affective disorders research . J Clin Psychopharmacol 1986;6:65-74.Crossref 9. Dilsaver SC: Cholinergic mechanisms in depression . Brain Res Rev 1986;11:285-316.Crossref 10. Dilsaver SC: Cholinergic mechanisms in affective disorders: Future directions for investigation . Acta Psychiatr Scand 1986;74:312-334.Crossref 11. Cohen BM, Baldessarini RJ: Tolerance to therapeutic effects of antidepressants . Am J Psychiatry 1985;142:489-490. 12. Tocco-Bradley R, Kluger MJ, Kauffman CA: Effect of age on fever: An acute phase response of rats to endotoxin and Salmonella typhimurium . Infect Immunol 1985;47:106-111. 13. Levy A, Zohar J, Belmaker RH: The effect of chronic lithium pretreatment on rat brain muscarinic receptor regulation . Neuropharmacology 1982;21:1199-1201.Crossref

Griez, Eric;Pols, Henk

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250112015

Abstract To the Editor.— Gorman and associates found that 15 minutes before a lactate infusion patients with PD had a lower inorganic phosphate (PO4) level than controls. Moreover, using a cutoff point of 0.73 mmol/L (2.25 mg/dL), post hoc analysis revealed a significantly greater proportion of low baseline PO4 levels among the lactate panicker patient group than in the nonpanicker group. The authors conclude that (1) low PO4 level is associated with PD and (2) the level of PO4 before a lactate infusion may be a predictor of subsequent lactate vulnerability. Rather than to a metabolic disturbance, the authors ascribe this hypophosphatemia to the HV, which occurred both during the lactate-induced panic attack and before the infusion.In a retrospective examination of 32 patients with PD, as determined by DSM III-R,1 we failed to find any hypophosphatemia. Mean venous PO4 level was 1.18 mmol/L (3.65 mg/dL) (SD, 0.18 References 1. American Psychiatric Association, Work Group to Revise DSM-III: Diagnostic and Statistical Manual of Mental Disorders , ed 3, Revised. Washington, DC, American Psychiatric Association, 1987. 2. Griez E, Pols HJ, van den Hout MA: Acid base balance in real life panic . J Affective Disord 1987;12:263-266.Crossref

Gorman, Jack M.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250112016

This article is only available in the PDF format. Download the PDF to view the article, as well as its associated figures and tables. Abstract In Reply.— The commments of Drs Bass and Gardner and Drs Griez and Pols add useful interpretations to our article. The former correctly note that a large body of work already attests to the association between anxiety disorder and HV. The latter support our conclusion that hypophosphatemia in patients with PD is probably a marker for HV.What is most striking, however, is that the two comments are directly contradictory. Drs Bass and Gardner affirm that "we have shown that some patients with agoraphobia and PD spend large portions of the waking day in the hypocapnic range," while Drs Griez and Pols state that "patients with PD do not hyperventilate between their attacks.... This was the case in our series... supported by blood gas studies that we recently completed."I am inclined to agree with Drs Bass and Gardner, who add the important qualifier "some patients" to their statement. Our data

Heston, Leonard L.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250113018pmid: 3337612

Abstract To the Editor.— Readers of the Archives should be advised to exercise caution before accepting the conclusions reached by Mohs et al1 regarding the morbid risk of first-degree relatives of persons with Alzheimer's disease. Mohs and coworkers conclude that the risk "approximates 50% by 90 years of age" and go on to suggest that "a common autosomal dominant gene" may be involved.There are two main reasons for doubting these conclusions. First, the risk of Alzheimer's disease in a member of the general population becomes substantial by 90 years of age; most estimates run between 20% and 30%. Therefore, much of the dementia observed by Mohs et al may be coincidental and totally unrelated to genes shared with Alzheimer's disease probands. Indeed, only five cases were observed with onset after 80 years of age among 26.5 relatives at risk at 80 years of age (Mohs and colleagues' Table 1), References 1. Mohs RC, Breitner JCS, Silverman JM, Davis KL: Alzheimer's disease: Morbid risk among first-degree relatives approximates 50% by 90 years of age . Arch Gen Psychiatry 1987;44:405-408.Crossref 2. Heston LL, Mastri AR, Anderson VE, White J: Dementia of the Alzheimer's type: Clinical genetics, natural history, and associated conditions . Arch Gen Psychiatry 1981;38:1085-1090.Crossref

Mohs, Richard C.;Breitner, John C. S.;Silverman, Jeremy M.;Davis, Kenneth L.

1988 Archives of General Psychiatry

doi: 10.1001/archpsyc.1988.01800250114019

Abstract In Reply.— Dr Heston has raised several interesting points regarding the methods and conclusions in our recent report concerning the morbid risk among first-degree relatives of patients with Alzheimer's disease. First, he suggests that the risk figures for first-degree relatives over 80 years of age are really not much greater than one would observe in the general population. He states that most population estimates run between 20% and 30% but cites no data. We are aware of no prospective studies indicating such high risks. Some studies indicate prevalence of all types of dementia as high as 22% after 80 years of age,1 but none of them suggests annual risks for Alzheimer's disease as high as the approximately 4% observed in first-degree relatives of Alzheimer's disease probands 80 to 86 years of age.Second, Dr Heston suggests that the risk among control relatives should be substracted from the risk among relatives References 1. Mortimer JA, Schuman LM, French LR: Epidemiology of dementing illness , in Mortimer JA, Schuman LM (eds): The Epidemiology of Dementia . New York, Oxford University Press Inc, 1981, pp 3-23. 2. Larrson T, Sjogren T, Jacobsen G: Senile dementia: A clinical, sociomedical, and genetic study . Acta Psychiatr Scand 1963;39( (suppl 167) ): 1-259. 3. Breitner JCS, Folstein MF, Murphy EA: Familial aggregation in Alzheimer dementia: II. Genetic implications of age-dependent expression . J Psychiatry Res 1986;20:45-55.Crossref 4. Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A: Pathological verification of ischemic score in differentiation of dementias . Ann Neurol 1980;7:486-488.Crossref 5. Silverman JM, Breitner JCS, Mohs RC, Davis KL: Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias . Am J Psychiatry 1986;143:1279-1282.