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Mixed Symptoms and Syndromes of Anxiety and Depression: Diagnostic, Prognostic, and Etiologic Issues

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Annals of Clinical Psychiatry

Abstract

Patients with comorbid symptoms of anxiety and depression are common in clinical practice, and yet they continue to pose a diagnostic and therapeutic challenge to clinicians and researchers alike. This article is intended as a comprehensive review of current knowledge derived from a vast body of clinical research regarding the diagnostic interrelationships of anxiety and depressive disorders at both syndromal and subsyndromal levels. The prognostic implications of comorbidity are also reviewed. Biological linkages between the two disorders are explored, and recent biological theories attempting to explain and integrate the two disorders are presented as well. The article concludes with suggestions for further research.

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REFERENCES

  1. Wittchen HU, Essau CA, Krieg JC: Anxiety disorders: similarities and differences of comorbidity in treated and untreated groups. Br J Psychiatry 1991; 159(Suppl 12): 23–33

    Google Scholar 

  2. Copp JE, Schwiderski UE, Robinson DS: Symptom comorbidity in anxiety and depressive disorders. J Clin Psychopharmacol 1990;10(3 suppl): 52S–60S

    Google Scholar 

  3. Clark LA: The anxiety and depressive disorders: descriptive psychopathology and differential diagnosis. In: Kendall PC, Watson D, eds. Anxiety and Depression: Distinctive and Overlapping Features. New York: Academic Press; 1989:83–129

    Google Scholar 

  4. APA: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994

    Google Scholar 

  5. Maier W, Rosenberg R, Argyle N, Buller R, Roth M, Brandon S, Benkert O: Subtyping panic disorder by major depression and avoidance behavior and the response to active treatment. Eur Arch Psychiatry Clin Neurosci 1991; 241:22–30

    Google Scholar 

  6. Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF: Phenelzine and imipramine in mood reactive depressives: Further delineation of the syndrome of atypical depression. Arch Gen Psychiatry 1989; 46:787–793

    Google Scholar 

  7. Fyer AJ, Liebowitz MR, Klein DF: Treatment trials, comorbidity, and syndromal complexity. In: Maser JD, Cloninger CR, eds. Comorbidity of Mood and Anxiety Disorders. Washington, DC: American Psychiatric Press; 1990:669–679

    Google Scholar 

  8. Brown TA, Barlow DH: Comorbidity among anxiety disorders: Implications for treatment and DSM-IV. J Consult Clin Psychol 1992; 60:835–844

    Google Scholar 

  9. Goldberg DP, Bridges K, Duncan-Jones P, Grayson D: Dimensions of neuroses seen in primary care settings. Psychol Med 1987; 17:461–470

    Google Scholar 

  10. Dobson KS: The relationship between anxiety and depression. Clin Psychol Rev 1985; 5:307–324

    Google Scholar 

  11. Clark LA, Watson D: Tripartite model of anxiety and depression: Psychosometric evidence and taxonomic implications. J Abnorm Psychol 1991; 100:316–336

    Google Scholar 

  12. Riskind JH, Beek AT, Brown G, Steer RA: Taking the measure of anxiety and depression: Validity of the reconstructed Hamilton scales. Nerv Ment Dis 1987; 175:474–479

    Google Scholar 

  13. Koeter MWJ, van den Brink W: The relationship between depression and anxiety: Construction of a prototypical anxiety and depression scale. Psychol Med 1992; 22:597–606

    Google Scholar 

  14. Akiskal HS: Toward a clinical understanding of the relationship of anxiety and depressive disorders. In: Maser JD, Cloninger CR, eds. Comorbidity of Mood and Anxiety Disorders. Washington, DC: American Psychiatric Press; 1990:597–607

    Google Scholar 

  15. Moras K, Barlow D: Definitions of secondary depression: Effects on comorbidity and outcome in anxiety disorders. Psychopharmacol Bull 1992; 28:27–33

    Google Scholar 

  16. APA: Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. Washington, DC: American Psychiatric Association; 1980

    Google Scholar 

  17. Winokur G: The concept of secondary depression and its relationship to comorbidity. Psychiatr Clin North Am 1990; 13:567–583

    Google Scholar 

  18. Stahl SM: Mixed anxiety and depression: Clinical implications, J Clin Psychiatry 1993; 54(Suppl):33–38

    Google Scholar 

  19. APA: Diagnostic and Statistical Manual of Mental Disorders (3rd ed—revised). Washington, DC: American Psychiatric Association; 1987

    Google Scholar 

  20. Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC: Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey: Arch Gen Psychiatry 1996; 53:159–168

    Google Scholar 

  21. Wittchen HU, Zhao S, Kessler RC, Eaton WW: DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51:355–364

    Google Scholar 

  22. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995; 52:1048–1060

    Google Scholar 

  23. Goisman RM, Warshaw MG, Peterson LG, Rogers MP, Cunco P, Hunt MF, Tomlin-Albanese JM, Kazim A, Gollan JK, Epstein-Kaye T, Reich JH, Keller MB: Panic, agoraphobia, and panic disorder with agoraphobia: Data from a multicenter anxiety disorders study. J Nerv Ment Dis 1994; 182:72–79

    Google Scholar 

  24. Massion AO, Warshaw MG, Keller MB: Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder. Am J Psychiatry 1993; 150:600–607

    Google Scholar 

  25. Warshaw MG, Fierman E, Pratt L, Hunt M, Yonkers KA, Massion AO, Keller MB: Quality of life and dissociation in anxiety disorder patients with histories of trauma or PTSD. Am J Psychiatry 1993; 150:1512–1516

    Google Scholar 

  26. Sanderson WC, Beck AT, Beck J: Syndrome comorbidity in patients with major depression or dysthymia: Prevalence and temporal relationships. Am J Psychiatry 1990; 147:1025–1028

    Google Scholar 

  27. Keller MB, Yonkers KA, Warshaw MG, Pratt LA, Gollan JK, Massion AO, White K, Swartz AR, Reich J, Lavori PW: Remission and relapse in subjects with panic disorder and panic disorder with agoraphobia: A prospective short-interval naturalistic follow-up. J Nerv Ment Dis 1994; 182:290–296

    Google Scholar 

  28. Robins LN, Locke BZ, Regier DA: An overview of psychiatric disorders in America. In: Robins LN, Regier DA, eds. Psychic Disorders in America. The Epidemiologic Catchment Area Study. New York: Free Press; 1991:328–366

    Google Scholar 

  29. Goisman RM, Warshaw MG, Steketee GS, Fierman EJ, Rogers MP, Goldenberg I, Weinshenker NJ, Vasile RG, Keller MB: DSM-IV and the disappearance of agoraphobia without a history of panic disorder: New data on a controversial diagnosis. Am J Psychiatry 1995; 152:1438–1443

    Google Scholar 

  30. Lesser IM: Panic disorder and depression: Co-occurrence and treatment. In: Ballenger J, ed. Clinical Aspects of Panic Disorder. New York: Wiley-Liss; 1990:181–191

    Google Scholar 

  31. Roy-Byrne PP, Cowley DS: Course and outcome in panic disorder: A review of recent follow-up studies. Anxiety 1995; 1:151–160

    Google Scholar 

  32. Breier A, Charney DS, Heninger GR: Agoraphobia with panic attacks: Development, diagnostic stability, and course of illness. Arch Gen Psychiatry 1986; 43:1029–1036

    Google Scholar 

  33. Blazer DG, Hughes D, George LK, Swartz M, Boyer R: Generalized anxiety disorder; 1991:180–203

  34. Eaton WM, Dryman A, Weissman MM: Panic and phobia. In: Robbins LN, Regier DA, eds. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York: Free Press; 1991:155–179

    Google Scholar 

  35. Shores MM, Glubin T, Cowley DS, Dager SR, Roy-Byrne PP, Dunner DL: The relationship between anxiety and depression: A clinical comparison of generalized anxiety disorder, dysthymic disorder, panic disorder, and major depressive disorder. Comp Psychiatry 1992; 33:237–244

    Google Scholar 

  36. Clark DA, Beck AT, Beck JS: Symptom differences in major depression, dysthymia, panic disorder, and generalized anxiety disorder. Am J Psychiatry 1994; 151:205–209

    Google Scholar 

  37. Riskind JH, Moore R, Harman B, Hohmann AA, Beck AT, Stewart B: The relation of generalized anxiety disorder to depression in generalized dysthymic disorder in particular. In: Rapee RM, Barlow DH, eds. Chronic Anxiety: Generalized Anxiety Disorder and Mixed Anxiety Depression. New York: Guilford Press; 1991:153–171

    Google Scholar 

  38. Markowitz JC: Comorbidity of dysthymia. Psychiatr Ann 1993; 23:617–624

    Google Scholar 

  39. Boyd JH, Burke JD Jr, Gruenburg E, Holzer CE III, Rae DS, George LK, Karno M, Stoltzman R, McEvoy L, Nestadt G: Exclusion criteria of DSM-III: A study of co-occurrence of hierarchy-free syndromes. Arch Gen Psychiatry 1984; 41:983–989

    Google Scholar 

  40. Buller R, Maier W, Benkert O: Clinical subtypes in panic disorder: Their descriptive and prospective validity. J Affect Disord 1986; 11:105–114

    Google Scholar 

  41. Noyes R, Reich J, Christiansen J, Suelzer M, Pfohl B, Coryell WA: Outcome of panic disorder: Relationship to diagnostic subtypes and comorbidity. Arch Gen Psychiatry 1990; 47:809–818

    Google Scholar 

  42. Lesser IM, Rubin RT, Pecknold JC, Rifkin A, Swinson RP, Lydiard RB, Burrows GD, Noyes R Jr, DuPont RL Jr: Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment. Arch Gen Psychiatry 1988; 45:437–443

    Google Scholar 

  43. Stein MB, Tancer ME, Uhde TW: Major depression in patients with panic disorder: Factors associated with course and recurrence. J Affect Disord 1990; 19:287–296

    Google Scholar 

  44. Fawcett J, Kravitz HM: Anxiety syndromes and their relationship to depressive illness. J Clin Psychiatry 1983; 44 (8, Pt 2):8–11

    Google Scholar 

  45. Roth M, Gurney C, Garside RF, Kerr TA: Studies in the classification of affective disorders: The relationship between anxiety states and depressive illnesses—I. Br J Psychiatry 1972; 121:147–161

    Google Scholar 

  46. Prusoff BA, Klerman GL: Differentiating depressed from anxious neurotic outpatients. Arch Gen Psychiatry 1974; 30:302–309

    Google Scholar 

  47. Fava GA, Kellner R: Symptoms in affective disorders. Am J Psychiatry 1991; 148:823–830

    Google Scholar 

  48. Clayton PJ, Grove WM, Coryell W, Keller M, Hirschfeld R, Fawcett J: Follow-up and family study of anxious depression. Am J Psychiatry 1991; 148:1512–1517

    Google Scholar 

  49. Joffe RT, Bagby RM, Levitt A: Anxious and nonanxious depression. Am J Psychiatry 1993; 150:1257–1258

    Google Scholar 

  50. Downing RW, Rickels K: Mixed anxiety-depression: Fact or myth? Arch Gen Psychiatry 1974; 30:312–317

    Google Scholar 

  51. Paykel ES: Classification of depressed patients: A cluster analysis derived grouping. Br J Psychiatry 1971; 118:275–288

    Google Scholar 

  52. Davidson J, Woodbury MA, Pelton S, Krishnan R: A study of depressive typologies using grade of membership analysis. Psychol Med 1988; 18:179–189

    Google Scholar 

  53. Blazer D, Swartz M, Woodbury M, Manton KG, Huges D, George LK: Depressive symptoms and depressive diagnoses in a community population: Use of a new procedure for analysis of psychiatric classification. Arch Gen Psychiatry 1988; 45:1078–1084

    Google Scholar 

  54. Liebowitz MR, Quitkin FM, Stewart JW, McGrath PJ, Harrison WM, Markowitz JS, Rabkin JG, Tricamo E, Goetz DM, Klein DF: Antidepressant specificity in atypical depression. Arch Gen Psychiatry 1988; 45:129–137

    Google Scholar 

  55. Davidson JR, Miller RD, Turnbull CD, Sullivan JL: Atypical depression. Arch Gen Psychiatry 1982; 39:527–534

    Google Scholar 

  56. Clancy J, Noyes R, Hoenk PR, Slymen DJ: Secondary depression in anxiety neurosis. J Nerv Ment Dis 1978; 166:846–850

    Google Scholar 

  57. Judd LL, Rapaport MH, Paulus MP, Brown JL: Subsyndromal symptomatic depression: A new mood disorder? J Clin Psychiatry 1994; 55(4S):18–28

    Google Scholar 

  58. Skodol AE, Schwartz S, Dohrenwend BP, Levav I, Shrout PE: Minor depression in a cohort of young adults in Israel. Arch Gen Psychiatry 1994; 51:542–551

    Google Scholar 

  59. Broadhead WE, Blazer DG, George LK, Tse CK: Depression, disability days, and days lost from work in a prospective epidemiologic survey. JAMA 1990; 264:2524–2528

    Google Scholar 

  60. Wittchen HU, Essau CA: Comorbidity and mixed anxiety depressive disorder: Is there epidemiologic evidence? J Clin Psychiatry 1993; 54(1S):9–15

    Google Scholar 

  61. Brown GW, Bifulco A, Harris TO: Life events, vulnerability, and onset of depression: Some refinements. Br J Psychiatry 1987; 150:30–42

    Google Scholar 

  62. Murphy JM, Olivier DC, Sobol AM, Monson RR, Leighton AH: Diagnosis and outcome: Depression and anxiety in a general population. Psychol Med 1986; 16:117–126

    Google Scholar 

  63. Von Korff M, Shapiro S, Burke JD, Teitlebaum M, Skinner EA, German P, Turner RW, Klein L, Burns B: Anxiety and depression in a primary care clinic: Comparison of Diagnostic Interview Schedule, Generalized Health Questionnaire, and practitioner assessments. Arch Gen Psychiatry 1987; 44:152–156

    Google Scholar 

  64. Ormel J, Koeter MW, van den Brink W, van de Willige G: Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry 1991; 48:700–706

    Google Scholar 

  65. Barrett JE, Barrett JA, Oxman TE, Gerber PD: The prevalence of psychiatric disorders in a primary care practice. Arch Gen Psychiatry 1988; 45:1100–1106

    Google Scholar 

  66. Ormel J, Oldehinkel T, Brilman E, van den Brink W: Outcome of depression and anxiety in primary care: A three-wave 31/2-year study of psychopathology and disability. Arch Gen Psychiatry 1993; 50:759–766

    Google Scholar 

  67. Murphy JM, Sobol AM, Olivier DC, Monson RR, Leighton AH, Pratt LA: Prodromes of depression and anxiety: The Stirling County study. Br J Psychiatry 1989; 155:490–495

    Google Scholar 

  68. Zinbarg RE, Barlow DH, Liebowitz M, Street L, Broadhead E, Katon W, Roy-Byrne P, Lepine J-P, Teherani M, Richards J, Brantley PJ, Kraemer H: The DSM-IV field trial for mixed anxiety-depression. Am J Psychiatry 1994; 151:1153–1162

    Google Scholar 

  69. Katon W, Roy-Byrne PP: Mixed anxiety and depression. J Abnorm Psychol 1991; 100:337–345

    Google Scholar 

  70. Preskorn SH, Fast GA: Beyond signs and symptoms: The case against a mixed anxiety and depression category. J Clin Psychiatry 1993; 54(1S):24–32

    Google Scholar 

  71. Zinbarg RE, Barlow DH: Mixed anxiety-depression: A new diagnostic category? In: Rapee RM, Barlow DH, eds. Chronic Anxiety, Generalized Anxiety Disorder, and Mixed Anxiety Depression. New York: Guilford Press; 1991:136–152

    Google Scholar 

  72. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Geneva, Switzerland: World Health Organization; 1992

  73. Stavrakaki C, Vargo B: The relationship of anxiety and depression: Review of the literature. Br J Clin Psychiatry 1986; 149:7–16

    Google Scholar 

  74. Clark LA, Watson D, Mineka S: Temperament, personality, and the mood and anxiety disorders. J Abnorm Psychol 1994; 103:103–116

    Google Scholar 

  75. Tyrer P: Neurosis divisible? Lancet 1985; 1:685–688

    Google Scholar 

  76. Tyrer P, Seivewright N, Ferguson B, Tyrer J: The general neurotic syndrome: A coaxial diagnosis of anxiety, depression, and personality disorder. Acta Psychiatr Scand 1992; 85:201–206

    Google Scholar 

  77. Brown GW, Harris TO, Hepworth C: Life events and endogenous depression: A puzzle reexamined. Arch Gen Psychiatry 1994; 51:525–534

    Google Scholar 

  78. Frank E, Anderson B, Reynolds CF, Ritenour A, Kupfer DJ: Life events and the Research Diagnostic Criteria endogenous subtype: A confirmation of the distinction using the Bedford College Methods. Arch Gen Psychiatry 1994; 51:519–524

    Google Scholar 

  79. Post RM: Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992; 149:999–1010

    Google Scholar 

  80. Coryell W, Endicott J, Andreasen NC, Keller MB, Clayton PJ, Hirschfeld RM, Scheftner WA, Winokur G: Depression and panic attacks: The significance of overlap as reflected in follow-up and family study data. Am J Psychiatry 1988; 145:293–300

    Google Scholar 

  81. Van Valkenburg C, Akiskal HS, Puzantian V, Rosenthal T: Anxious depressions: Clinical, family history, and naturalistic outcome—Comparisons with panic and major depressive disorders. J Affect Disord 1984; 6:67–82

    Google Scholar 

  82. Garvey M, Cook B, Noyes R: Comparison of major depressive patients with a predominantly sad versus anxious mood. J Affect Disord 1989; 17:183–187

    Google Scholar 

  83. Weissman MM, Klerman GL, Markowitz JS, Ouellette R: Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med 1989; 321:1209–1214

    Google Scholar 

  84. Cox BJ, Direnfeld DM, Swinson RP, Norton GR: Suicidal ideation and suicide attempts in panic disorder and social phobia. Am J Psychiatry 1994; 151:882–887

    Google Scholar 

  85. Vollrath M, Angst J: Outcome of panic and depression in a seven-year followup: Results of the Zurich study. Acta Psychiatr Scand 1989; 80:591–596

    Google Scholar 

  86. Fawcett J: Predictors of early suicide: Identification and appropriate intervention. J Clin Psychiatry 1988; 49(10S):7–8

    Google Scholar 

  87. Warshaw MG, Massion AO, Peterson LG, Pratt LA, Keller MB: Suicidal behavior in patients with panic disorder: Retrospective and prospective data. J Affect Disord 1995; 34:235–247

    Google Scholar 

  88. Friedman S, Jones JC, Chernen L, Barlow DH: Suicidal ideation and suicide attempts among patients with panic disorder: A survey of two outpatient clinics. Am J Psychiatry 1992; 149:680–685

    Google Scholar 

  89. Gurney C, Roth M, Garside RF, Kerr TA, Schapira K: Studies in the classification of affective disorders: The relationship between anxiety states and depressive illnesses. II. Br J Psychiatry 1972; 121:162–166

    Google Scholar 

  90. Hecht H, von Zerssen D, Wittchen HU: Anxiety and depression in a community sample: The influence of comorbidity on social functioning. J Affect Disord 1990; 18:137–144

    Google Scholar 

  91. Noyes R, Clancy J, Woodman C, Holt CS, Suelzer M, Christiansen J, Anderson DJ: Environmental factors related to the outcome of panic disorder: A seven-year follow-up study. J Nerv Ment Dis 1993; 181:529–538

    Google Scholar 

  92. Rogers MP, White K, Warshaw MG, Yonkers KA, Rodriguez-Villa F, Chang G, Keller MB: Prevalence and medical illnesses in patients with anxiety disorders. Int J Psychiatry Med 1994; 24:83–96

    Google Scholar 

  93. Brown C, Schulberg HC, Madonia MJ, Shear MK, Houck PR: Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Am J Psychiatry 1996; 153:1293–1300

    Google Scholar 

  94. Reich J, Perry JC, Shera D, Dyck I, Vasile R, Goisman RM, Rodriguez-Villa F, Massion AO, Keller M: Comparison of personality disorders in different anxiety disorder diagnoses: Panic, agoraphobia, generalized anxiety, and social phobia. Ann Clin Psychiatry 1994; 6:125–134

    Google Scholar 

  95. Kessler RC, Foster CL, Saunders WB, Stang PE: Social consequences of psychiatric disorders, I: Educational attainment. Am J Psychiatry 1995; 152:1026–1032

    Google Scholar 

  96. Ormel J, von Korff M, van den Brink W, Katon W, Brilman E, Oldehinkel T: Depression, anxiety and social disability show synchrony of change in primary care patients. Am J Public Health 1993; 83:385–390

    Google Scholar 

  97. Smith CUM: Elements of Molecular Biology. New York: John Wiley and Sons; 1989

    Google Scholar 

  98. Trivedi MH: Functional neuroanatomy of obsessive-compulsive disorder. J Clin Psychiatry 1996; 57(Suppl 8):26–36

    Google Scholar 

  99. Goddard AW, Charney DS: Toward an integrated neurobiology of panic disorder. J Clin Psychiatry 1997; 58(Suppl 2):4–11

    Google Scholar 

  100. Sapolsky RM: Why stress is bad for your brain. Science 1996; 273:749–750

    Google Scholar 

  101. Gorman JM, Liebowitz MR, Fyer AJ, Stein J: A neuroanatomical hypothesis for panic disorder. Am J Psychiatry 1989; 146:148–161

    Google Scholar 

  102. Breier A, Paul SM: The GABAA-benzodiazepine receptor: Implications for the molecular basis of anxiety. J Psychiatr Res 1990; 24(2S):91–104

    Google Scholar 

  103. Teicher MH: Biology of anxiety. Med Clin North Am 1988; 72:791–814

    Google Scholar 

  104. Gray JA: The long-term effects of stress: The relation between anxiety and depression. In: The Neuropsychology of Anxiety: An Enquiry Into the Functions of the Septo-Hippocampal System. New York: Oxford University Press; 1982:374–408

    Google Scholar 

  105. Weiss JM, Stout JC, Aaron MF, Quan N, Owens MJ, Butler PD, Nemeroff CB: Depression and anxiety: Role of the locus ceruleus and corticotropin-releasing factor. Brain Res Bull 1994; 35:561–572

    Google Scholar 

  106. Paul SM: Anxiety and depression: A common neurobiological substrate? J Clin Psychiatr 1988; 49(10S):13–16

    Google Scholar 

  107. Roy-Byrne PP, Cowley DS, Greenblatt DJ, Shader RI, Hommer D: Reduced benzodiazepine sensitivity in panic disorder. Arch Gen Psychiatry 1990; 47:534–538

    Google Scholar 

  108. Bolden SW, Hambley JW, Johnston GAR, Rogers LJ: Neonatal stress and long-term modulation of GABA receptors in rat brain. Neurosci Lett 1990; 111:258–262

    Google Scholar 

  109. Petty F, Davis LL, Kabel D, Krazner GL: Serotonin dysfunction disorders: A behavioral neurochemistry perspective. J Clin Psychiatry 1996; 57(Suppl 8):11–16

    Google Scholar 

  110. Roy-Byrne PP, Uhde TW, Post RM, Galluci W, Chrousos GP, Gold PW: The corticotropin-releasing hormone stimulation test in patients with panic disorders. Am J Psychiatry 1986; 143:896–899

    Google Scholar 

  111. Owens MJ, Vargas MA, Knight DL, Nemeroff CB: The effects of alprazolam on corticotropin-releasing factor neurons in the rat brain: Acute time course, chronic treatment and abrupt withdrawal. J Pharmacol Exp Ther 1991; 258:349–356

    Google Scholar 

  112. Chalmers DT, Lovenberg TW, Grigoriadis DE, Behan DP, De Souza EB: Corticotropin-releasing factor receptors: From molecular biology to drug design. Trends Pharmacol Sci 1996; 17:166–172

    Google Scholar 

  113. Lydiard RB: Neuropeptides and anxiety: Focus on cholecystokinin. Clin Chem 1994; 40:315–318

    Google Scholar 

  114. Abelson JL: Cholecystokinin in psychiatric research: A time for cautious excitement. J Psychiatr Res 1995; 9:389–396

    Google Scholar 

  115. Grasing K, Murphy MG, Linn J, Swigar M, Freedholm D, Clarke L, Zhang J, Wolkowitz OM, Weingartner H, Putnam K, Seibold JR: Human pharmacokinetics and tolerability of L-365, 260, a novel cholecystokinin-B antagonist. J Clin Pharmacol 1996; 36:292–300

    Google Scholar 

  116. Adams JB, Pyke RE, Costa J, Cutler NR, Schweizer E, Wilcox CE, Wisselink PG, Greiner M, Pierce MW, Pande AC: A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-998, in patients with generalized anxiety disorder. J Clin Psychopharmacol 1995; 15:428–434

    Google Scholar 

  117. Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J, Chenault A, Shrivastava R, Matzura-Wolfe D, Lines C, Reines S: A placebo-controlled trial of L-365,260, a CCKB antagonist, in panic disorder. Biol Psychiatry 1995; 37:462–466

    Google Scholar 

  118. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB: MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995; 152:973–981

    Google Scholar 

  119. Gurvits TV, Shenton ME, Hokama H, Ohta H, Lasko NB, Gilbertson MW, Orr SP, Kikinis R, Jolesz FA, McCarley RW, Pitman RK: Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry 1996; 40:1091–1099.

    Google Scholar 

  120. Bremner D, Randall P, Vermetten E, Staib L, Broner RA, Mazure C, Capelli S, McCarthy G, Izulis RB, Charney DS: Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse—A preliminary report. Biol Psychiatry 1997; 41:23–32

    Google Scholar 

  121. Sheline YI, Wang PW, Gado MH, Csernansky JG: Hippocampal atrophy in major depression. Proc Natl Acad Sci USA 1996; 93:3908–3913

    Google Scholar 

  122. Stein-Behrens, Mattson MP, Chang I, Yeh M, Sapolsky R: Stress exacerbates neuron loss and cytoskeletal pathology in the hippocampus. J Neurosci 1994; 14:5373–5380

    Google Scholar 

  123. Soares JC, Mann JJ: The anatomy of mood disorders—Review of structural neuroimaging studies. Biol Psychiatry 1997; 41:86–106

    Google Scholar 

  124. Alloy LB, Kelly KA, Mineka S, Clements CM: Comorbidity of anxiety and depressive disorders: A helplessness-hopelessness perspective. In: Maser JD, Cloniniger CR, eds. Comorbidity of Mood and Anxiety Disorders. Washington, DC: American Psychiatric Press; 1990:499–543

    Google Scholar 

  125. Breier A, Charney DS, Heninger GR: The diagnostic validity of anxiety disorders and their relationship to depressive illness. Am J Psychiatry 1985; 142:787–797

    Google Scholar 

  126. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ: Major depression and generalized anxiety disorder: Same genes, (partly) different environments? Arch Gen Psychiatry 1992; 49:716–722

    Google Scholar 

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Barbee, J.G. Mixed Symptoms and Syndromes of Anxiety and Depression: Diagnostic, Prognostic, and Etiologic Issues. Ann Clin Psychiatry 10, 15–29 (1998). https://doi.org/10.1023/A:1026198512361

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