Spontaneous Recurrence of Methamphetamine-lnduced Paranoid-Hallucinatory States in Female Subjects: Susceptibility to Psychotic States and Implications for Relapse of Schizophrenia

 

 Buy Article Permissions and Reprints

In this study, we examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). The subjects were 81 physically healthy females. Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had undergone frightening and stressful experiences during previous MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers, the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while the 11 with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization, and also noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model psychosis is a potential tool for validating basic neurobiological concepts thought to be related to the schizophrenia. A better understanding of the neurobiological mechanisms of susceptibility to recurrence could provide useful information in the development of strategies for preventing relapse.

References

• 1 Abercrombie E D, Jacobs B L. Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. 1. Acutely presented stressful and nonstressful stimuli.  J Neurosci. 1987;  7 2837-2843
  PubMedGoogle Scholar
• 2 Andermann L F, Savard G, Meencke H J, McLachlan R, Moshé S, Andermann F. Psychosis after resection of ganglioglioma or DENT: evidence for an association.  Epilepsia. 1999;  40 83-87
  PubMedGoogle Scholar
• 3 Anisman H, Zacharko R M. Behavioral and neurochemical consequences associated with stressors.  Ann NY Acad Sci. 1995;  771 205-225
  PubMedGoogle Scholar
• 4 Asaad G, Shapiro B. Hallucinations: theoretical and clinical overview.  Am J Psychiatry. 1986;  143 1088-1097
  PubMedGoogle Scholar
• 5 Bell D S. Comparison of amphetamine psychosis and schizophrenia.  Br J Psychiatry. 1965;  111 701-707
  PubMedGoogle Scholar
• 6 Breier A, Buchanan R W, Waltrip II R W, Listwak S, Holmes C, Goldstein D S. The effect of clozapine on plasma norepinephrine: relationship to clinical efficacy.  Neuropsychopharmacology. 1994;  10 1-7
  PubMedGoogle Scholar
• 7 Bremner J D, Krystal J H, Southwick S M, Charney D S. Functional neuroanatomical correlates of the effects of stress on memory.  J Traumatic Stress. 1995;  8 527-553
  PubMedGoogle Scholar
• 8 Brown A S, Gewirtz G, Harkavy-Friedman J, Cooper T, Brébion G, Amador X F, Malaspina D, Gorman J M. Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol.  Neuropsychopharmacology. 1987;  17 317-325
  PubMedGoogle Scholar
• 9 Castellani S, Ziegler M G, van Kammen D P, Alexander P E, Siris S G, Lake C R. Plasma norepinephrine and dopamine-β-hydroxylase activity in schizophrenia.  Arch Gen Psychiatry. 1982;  39 1145-1149
  PubMedGoogle Scholar
• 10 Charpusta S J, Wyatt R J, Masserano J M. Effects of single and repeated footshock on dopamine release and metabolism in the brains of fisher rats.  J Neurochem. 1997;  68 2024-2031
  PubMedGoogle Scholar
• 11 Dalmaz Y, Peyrin L. Relations entre la 3-méthoxytyramine urinaire et le metabolisme péripherioque de la dopamine chez l'homme et chez l'enfant.  Archiv Inter Physiol Biochim. 1978;  86 257-270
  PubMedGoogle Scholar
• 12 Dimsdale J E, Moss J. Plasma catecholamines in stress and exercise.  JAMA. 1980;  243 340-342
  CrossrefPubMedGoogle Scholar
• 13 Gouzoulis-Mayfrank E, Hermle L, Thelen B, Sass H. History, rationale and potential of human experimental hallucinogenic drug research in psychiatry.  Pharmacopsychiatry. 1998;  31 (2 Suppl) 63-68
  PubMedGoogle Scholar
• 14 Green A I, Alam M Y, Boshes R A, Waternaux C, Pappalardo K M, Fitzgibbon M E, Tsuang M T, Schildkraut J J. Haloperidol response and plasma catecholamines and their metabolites.  Schizophr Res. 1993;  10 33-37
  CrossrefPubMedGoogle Scholar
• 15 Havilcek L L, Crain R D. Practical statistics for physical sciences. American Chemical Society, Washington DC 1988
  Google Scholar
• 16 Heal D J, Frankland A TJ, Buckett W R. A new and highly sensitive method for measuring 3-methoxytyramine using HPLC with electrochemical detention studies with drugs which alter dopamine metabolism in the brain.  Neuropharmacology. 1990;  29 1141-1150
  CrossrefPubMedGoogle Scholar
• 17 Holroyd S H, Rabins P, Finkelstein D, Nicholson M C, Chase G A, Wisniewski S C. Visual hallucinations in patients with macular degeneration.  Am J psychiatry. 1992;  149 1701-1706
  PubMedGoogle Scholar
• 18 Holsten F. Flashbacks: a personal follow-up.  Arch Psychiatr Nervenkr. 1976;  222 293-304
  CrossrefPubMedGoogle Scholar
• 19 Irwin J, Ahiluwalia P, Anisman H. Sensitization of norepinephrine activity following acute and chronic footshock.  Brain Res. 1986;  379 98-103
  CrossrefPubMedGoogle Scholar
• 20 Javitt D C, Zukin S R. Recent advances in the phencyclidine model of schizophrenia.  Am J Psychiatry. 1991;  148 1301-1308
  PubMedGoogle Scholar
• 21 Kent A P, Stern G M, Webster R A. The effect of benserazide on the peripheral and central distribution and metabolism of lovodopa after acute and chronic administration in the rat.  Br J Pharmacol. 1990;  100 743-748
  PubMedGoogle Scholar
• 22 Landau S L. International dictionary of medicine and biology. A Wiley Medical Publication, New York, Chichester, Brisbane, Toronto, Singapore 1986 III
  Google Scholar
• 23 Laruelle M. The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies.  Brain Res Rev. 2000;  31 371-384
  CrossrefPubMedGoogle Scholar
• 24 Lieberman J A, Kinon B J, Loebel A D. Dopammergic mechanisms in idiopathic and drug-induced psychoses.  Schizophr Bull. 1990;  16 97-110
  PubMedGoogle Scholar
• 25 Lieberman J A, Sheitman B B, Kinon B J. Neurochemical sensitization in the pathophysiology of schizophrenia: deficit and dysfunction in neuronal regulation and plasticity.  Neuropsychopharmacology. 1997;  17 205-229
  CrossrefPubMedGoogle Scholar
• 26 Maeda S, Miyauchi J, Sakane M, Satto M, Maki S, Goto K, Matsuda M. Does endothelin-1 participate in the exercise-induced changes of blood flow distribution of muscles in humans?.  J Appl Physiol. 1997;  82 1107-1111
  PubMedGoogle Scholar
• 27 Matefy R E, Hayes C, Hirsh J. Psychedelic drug flashbacks, subjective reports and biographical data.  Addict Behav. 1978;  3 165-178
  CrossrefPubMedGoogle Scholar
• 28 Millns H, Woodward M, Bolton-Smith C. Is it necessary to transform nutrient variables prior to statistical analyses?.  Am J Epidemiol. 1995;  141 251-262
  PubMedGoogle Scholar
• 29 Nagaoka S, Iwamoto N, Arai H. First-episode neuroleptic-free schizophrenics: concentrations of monoamines and their metabolites in plasma and their correlations with clinical response to halopendol treatment.  Biol Psychiatry. 1997;  41 857-864
  CrossrefPubMedGoogle Scholar
• 30 Nuechterlein K H, Dawson M E, Ventura J, Gitlin M, Subotnik K L, Snyder K S, Mintz J, Bartzokis G. The vulnerability/stress model of schizophrenic relapse: a longitudinal study.  Acta Psychiatr Scand. 1994;  89 58-64
  PubMedGoogle Scholar
• 31 Ohashi H. Prison health issues: agenda item 2, the 15^th Asian and Pacific Conference of Correctional Administrators (in Japanese).  Japanese Journal of Correction. 1996;  107 36-46
  PubMedGoogle Scholar
• 32 Ozawa A. Normal and abnormal values: Catecholammes. Sogonnsho (in Japanese).  [General Practice of Medicine]. 1991;  40 1332-1338
  PubMedGoogle Scholar
• 33 Péronnet F, Blier P, Brisson G, Diamond P, Ledoux M, Volle M. Plasma catecholammes at rest and exercise in subjects with high- and low-trait anxiety.  Psychosom Med. 1986;  48 52-58
  PubMedGoogle Scholar
• 34 Petty F, Chae Y -I, Kramer C, Jordan S, Wilson L. Learned helplessness sensitizes hippocampal norepinephrine to mild restress.  Biol Psychiatry. 1994;  35 903-908
  CrossrefPubMedGoogle Scholar
• 35 Post R M. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.  Am J Psychiatry. 1992;  149 999-1010
  PubMedGoogle Scholar
• 36 Risbo A, Jessen K, Hagelsten J O. Catechoiamine response to the clinical use of alpha adrenergic receptor blocking agents.  Acta Anaesthesiol Scand. 1983;  27 72-74
  PubMedGoogle Scholar
• 37 Robinson T E, Becker J B, Young E A, Akii H, Castaneda E. The effects of footshock stress on regional brain dopamine metabolism and pituitary (β-endorphin release in rats previously sensitized to amphetamine.  Neuropharmacology. 1987;  26 679-691
  CrossrefPubMedGoogle Scholar
• 38 Roy A, Pickar D, Jong J D, Karoum F, Linnoila M. Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine.  Arch Gen Psychiatry. 1988;  45 849-857
  PubMedGoogle Scholar
• 39 Sato M, Numachi Y, Hamamura T. Relapse of paranoid psychotic state in methamphetamine model of schizophrenia.  Schizophr Bull. 1992;  18 115-122
  PubMedGoogle Scholar
• 40 Segal D S, Janowsky D S. Psychostimulant-induced behavioral effects: possible models of schizophrenia. In: Lipton MA, DiMascio A, Killam KF: Psychopharmacology: a generation of progress. Rave Press, New York 1978: 1113-1123
  Google Scholar
• 41 Southwick S M, Krystal J H, Morgan A, Johnson D, Nagy L M, Nicolaou A, Heninger G R, Charney D S. Abnormal noradrenergic function in posttraumatic stress disorder.  Arch Gen Psychiatry. 1993;  50 266-274
  PubMedGoogle Scholar
• 42 Spielberger C D. Manual for the State-Trait Anxiety Inventory. Consulting Psychologist Press. Palo Alto, California 1983
  Google Scholar
• 43 Taylor D C. Mental state and temporal lobe epilepsy: a correlative account of 100 patients treated surgically.  Epilepsia. 1972;  13 727-765
  PubMedGoogle Scholar
• 44 Thurm I, Haefner H. Perceived vulnerability, relapse risk and coping in schizophrenia: an explorative study.  Eur Arch Psychiatr Neurol Sci. 1987;  237 46-53
  CrossrefPubMedGoogle Scholar
• 45 Tuck J R. Effects of chlorpromazine, thioridazine and haloperidol on adrenergic transmitter mechanisms in man.  Eur J Clin Pharmacol. 1973;  6 81-87
  CrossrefPubMedGoogle Scholar
• 46 van der Kolk B A, Fisler R. Dissociation and fragmentary nature of traumatic memories: overview and exploratory study.  J Traumatic Stress. 1995;  8 505-525
  CrossrefPubMedGoogle Scholar
• 47 van Kammen D P. The biochemical basis of relapse and drug response in schizophrenia: review and hypothesis.  Psychol Med. 1991;  21 881-895
  PubMedGoogle Scholar
• 48 van Kammen D P, Ågren H, Yao J K, O'Connor D T, Gurklis J, Peters J L. Noradrenergic activity and prediction of psychotic relapse following haloperidol withdrawal in schizophrenia.  Am J Psychiatry. 1994;  151 379-384
  PubMedGoogle Scholar
• 49 von Voigtlander P F, Burian M A, Althaus T S, Williams L R. Effects of chronic haloperidol on vitamin E levels and monoamine metabolism in rats fed normal and vitamin E deficient diets.  Res Commun Chem Pathol Pharmacol. 1990;  68 343-352
  PubMedGoogle Scholar
• 50 Wang M T, Yoshioka M, Imai K, Tamura Z. Gas-liquid chromatographic and mass fragmentographic determination of 3-O-methylated catecholamines in human plasma.  Clin Chim Acta. 1975;  63 21-27
  CrossrefPubMedGoogle Scholar
• 51 Westerink B HC, Spaan S J. On the significance of endogenous 3-methoxytyramine for the effects of centrally acting drugs on dopamine release in the rat brain.  J Neurochem. 1982;  38 680-686
  PubMedGoogle Scholar
• 52 Wood P L, Altar C A. Dopamine release in vivo from nigrostriatal, mesolimbic, and mesocortical neurons utility of 3-methoxytyramine measurements.  Pharmacol Rev. 1988;  40 163-187
  PubMedGoogle Scholar
• 53 Yui K, Goto K, Ikemoto S, Ishiguro T. Methamphetamine psychosis: spontaneous recurrence of paranoid-hallucinatory states and monoamine neuro transmitter function.  J Clin Psychopharmacol. 1997;  17 34-43
  CrossrefPubMedGoogle Scholar
• 54 Yui K, Goto K, Ikemoto S, Ishiguro T, Angrist B, Duncan G E, Sheitman B B, Lieberman J A, Bracha S H, Ali S F. Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization.  Mol Psychiatr. 1999;  4 512-523
  CrossrefPubMedGoogle Scholar
• 55 Yui K, Goto K, Ikemoto S, Ishiguro T. Increased sensitivity to stress in spontaneous recurrence of methamphetamine psychosis: noradrenergic hyperactivity with contribution from dopaminergic hyperactivity.  J Clin Psychopharmacol. 2000;  20 165-174
  CrossrefPubMedGoogle Scholar

Kunio Yui

Department of Psychiatry, Jichi Medical School

Minamikawachi 3311-1

Tochigi 329-0498

Japan

Phone: +81 (48) 862-7520

Fax: +81 (48) 836-1372

Email: nibrin@jichi.ac.jp