Pharmacopsychiatry 2004; 37: 157-164
DOI: 10.1055/s-2004-832671
Affective Disorders
© Georg Thieme Verlag KG Stuttgart · New York

Mechanisms of Action in the Prevention of Recurrent Mood Disorders

B. Baumann1 , D. Krell1 , H. Dobrowolny1 , H. Bielau1
  • 1Department for Psychiatry and Psychotherapy, Otto-von-Guericke-Universität, Leipziger Straße 44, Magdeburg, Germany
Further Information

Publication History

Publication Date:
16 November 2004 (online)

Background: Since long-term treatment is a need in many patients with mood disorders, knowledge on mechanisms of action in the prevention of recurrence is of major relevance. Methods: Follow-up studies, which are best suited to prove the linkage of causal factors and mechanisms with the clinical course of the disorders, are rare. Another approach to search for preventive mechanisms is to address actions of pharmacological agents, which are effective in prophylactic treatment of mood disorders. Studies over the past several years have indicated that intracellular signaling cascades mediate long-term pharmacological effects via modulation of transcription factors and gene expression of neurotrophic and neuroprotective factors which may interfere with recurrence of affective illness. Results: The impact of treatment on stress responsive systems varies with different therapeutic strategies and the relevance of a treatment-related modification of stress reliability for the course of the disease is not clear. Functional and structural actions of mood stabilizers and of antidepressants on mood-relevant anatomical circuits and modulation of chronobiological alteraltions also appear to be involved in preventive mechanisms in mood disorders. Moreover, cognitive mediators of prophylactic effects have been described. Conclusion: Combined clinical and biological studies should assess the relevance of those modes of action for the long-term course of mood disorders.

References

  • 1 Angst J, Sellaro R. Historical perspectives and natural history of bipolar disorder.  Biol Psychiatry. 2000;  48 445-457
  • 2 Baumann B, Bogerts B. Neuroanatomical studies on bipolar disorder.  Br J Psychiatry. 2001;  178 142-147
  • 3 Bauwens F, Pardoen D, Staner L, Dramaix M, Mendlewicz J. Social adjustment and the course of affective illness: a one-year controlled longitudinal study involving bipolar and unipolar outpatients.  Depress Anxiety. 1998;  8 50-57
  • 4 Benca R M, Obermeyer W H, Thisted R A, Gillin J C. Sleep and psychiatric disorders. A meta-analysis.  Arch Gen Psychiatry. 1992;  49 651-668
  • 5 Bernstein H G, Heinemann A, Krell D, Mawrin C, Bielau H, Danos P. et al . Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients.  Ann N Y Acad Sci. 2002;  973 91-93
  • 6 Bowley M P, Drevets W C, Ongur D, Price J L. Low glial numbers in the amygdala in major depressive disorder.  Biol Psychiatry. 2002;  52 404-412
  • 7 Brown G M, Seggie J. Effects of antidepressants on entrainment of circadian rhythms.  Prog Neuropsychopharmacol Biol Psychiatry. 1988;  12 299-306
  • 8 Bschor T, Adli M, Baethge C, Eichmann U, Ising M, Uhr M. et al . Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.  Neuropsychopharmacology. 2002;  27 470-478
  • 9 Bschor T, Baethge C, Adli M, Eichmann U, Ising M, Uhr M. et al . Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression.  Depress Anxiety. 2003;  17 43-48
  • 10 Bunney W E, Bunney B G. Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression.  Neuropsychopharmacology. 2000;  22 335-345
  • 11 Chen G, Yuan P X, Jiang Y M, Huang L D, Manji H K. Lithium increases tyrosine hydroxylase levels both in vivo and in vitro.  J Neurochem. 1998;  70 1768-1771
  • 12 Coryell W, Turvey C, Endicott J, Leon A C, Mueller T, Solomon D. et al . Bipolar I affective disorder: predictors of outcome after 15 years.  J Affect Disord. 1998;  50 109-116
  • 13 Coyle J T, Duman R S. Finding the intracellular signaling pathways affected by mood disorder treatments.  Neuron. 2003;  38 157-160
  • 14 Dawe G S, Huff K D, Vandergriff J L, Sharp T, O’Neill M J, Rasmussen K. Olanzapine activates the rat locus coeruleus: in vivo electrophysiology and c-Fos immunoreactivity.  Biol Psychiatry. 2001;  50 510-520
  • 15 Deshauer D, Duffy A, Alda M, Grof E, Albuquerque J, Grof P. The cortisol awakening response in bipolar illness: a pilot study.  Can J Psychiatry. 2003;  48 462 - 466
  • 16 Drevets W C, Bogers W, Raichle M E. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism.  Eur Neuropsychopharmacol. 2002;  12 527-544
  • 17 Duman R S, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment.  Neuropsychopharmacology. 2001;  25 836-844
  • 18 Florkowski C M, Crozier I G, Nightingale S, Evans M J, Ellis M J, Joyce P. et al . Plasma cortisol, PRL, ACTH, AVP and corticotrophin releasing hormone responses to direct current cardioversion and electroconvulsive therapy.  Clin Endocrinol (Oxf). 1996;  44 163-168
  • 19 Frank E, Swartz H A, Kupfer D J. Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder.  Biol Psychiatry. 2000;  48 593-604
  • 20 Frankl V E. Man’s Search for Meaning: An Introduction to Logotherapy. 3rd ed. 1983 New York; Simon and Schuster 1984
  • 21 Freiman T M, Kukolja J, Heinemeyer J, Eckhardt K, Aranda H, Rominger A. et al . Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.  Naunyn Schmiedebergs Arch Pharmacol. 2001;  363 537-542
  • 22 Ghaemi S N, Boiman E E, Goodwin F K. Kindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder.  Biol Psychiatry. 1999;  45 137-144
  • 23 Gilad G M, Gilad V H. Overview of the brain polyamine-stress-response: regulation, development, and modulation by lithium and role in cell survival.  Cell Mol Neurobiol. 2003;  23 637-649
  • 24 Golombek D A, Ferreyra G A, Agostino P V, Murad A D, Rubio M F, Pizzio G A. et al . From light to genes: moving the hands of the circadian clock.  Front Biosci. 2003;  8 285-293
  • 25 Gomez F, Grauges P, Martin M, Armario A. The effect of chronic administration of antidepressants on the circadian pattern of corticosterone in the rat.  Psychopharmacology (Berl). 1998;  140 127-134
  • 26 Goodwin F K, Jamison K R. Manic depressive illness. New York; Oxford University Press 1999
  • 27 Gould T D, Manji H K. Signaling networks in the pathophysiology and treatment of mood disorders.  J Psychosom Res. 2002;  53 687-697
  • 28 Gray N A, Zhou R, Du J, Moore G J, Manji H K. The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders.  J Clin Psychiatry. 2003;  Suppl 5 3-17
  • 29 Harmer C J, Bhagwagar Z, Shelley N, Cowen P J. Contrasting effects of citalopram and reboxetine on waking salivary cortisol.  Psychopharmacology (Berl). 2003;  167 112-114
  • 30 Hatzinger M, Hemmeter U M, Baumann K, Brand S, Holsboer-Trachsler E. The combined DEX-CRH test in treatment course and long-term outcome of major depression.  J Psychiatr Res. 2002;  36 287-297
  • 31 Holsboer F, Barden N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation.  Endocr Rev. 1996;  17 187-205
  • 32 Ketter T A, Manji H K, Post R M. Potential mechanisms of action of lamotrigine in the treatment of bipolar disorders.  J Clin Psychopharmacol. 2003;  23 484-495
  • 33 Kitayama I, Yaga T, Kayahara T, Nakano K, Murase S, Otani M, Nomura J. Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex.  Biol Psychiatry. 1997;  42 687-696
  • 34 Kripke D F, Mullaney D J, Atkinson M, Wolf S. Circadian rhythm disorders in manic-depressives.  Biol Psychiatry. 1978;  13 335-351
  • 35 Kulhara P, Basu D, Mattoo S K, Sharan P, Chopra R. Lithium prophylaxis of recurrent bipolar affective disorder: long-term outcome and its psychosocial correlates.  J Affect Disord. 1999;  54 87-96
  • 36 Lara N, Archer S L, Baker G B, Le Melledo J M. Paroxetine-induced increase in metabolic end products of nitric oxide.  J Clin Psychopharmacol. 2003;  23 408-412
  • 37 Leibenluft E, Suppes T. Treating bipolar illness: focus on treatment algorithms and management of the sleep-wake cycle.  Am J Psychiatry. 1999;  156 1976-1981
  • 38 Mannel M, Muller-Oerlinghausen B, Czernik A, Sauer H. 5-HT brain function in affective disorder: d,l-fenfluramine-induced hormone release and clinical outcome in long-term lithium/carbamazepine prophylaxis.  J Affect Disord. 1997;  46 101-113
  • 39 Meltzer H Y. Dopamine, serotonin and glucorticoids and the psychopathology of schizophrenia. In Fog R, Gerlach J, editors Schizophrenia. Alfred Bunsen Symposium 38. Copenhagen; Munksgaard 1995: 74-91
  • 40 Moore G J, Bebchuk J M, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds I B. et al . Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects.  Biol Psychiatry. 2000;  48 1-8
  • 41 Moore G J, Bebchuk J M, Wilds I B, Chen G, Manji H K. Lithium-induced increase in human brain grey matter.  Lancet. 2000;  356 1241-1242
  • 42 Morin L P. Serotonin and the regulation of mammalian circadian rhythmicity.  Ann Med. 1999;  31 12-33
  • 43 Nagayama H, Lu J Q. Circadian rhythm in the responsiveness of central 5-HT2A receptor to DOI in rats.  Psychopharmacology (Berl). 1996;  127 113-116
  • 44 Nofzinger E A. Sleep and biological rhythms in bipolar disorder. In Soares J-C, Gershon S, editors Bipolar Disorders: Basic mechanisms and therapeutic implications. New York: Basel; 2000: 253-271
  • 45 Norrholm S D, Ouimet C C. Altered dendritic spine density in animal models of depression and in response to antidepressant treatment.  Synapse. 2001;  42 151-163
  • 46 O’Donohue T L, Wirz-Justice A, Kafka M S, Naber D, Campbell I C, Wehr T A. Effects of chronic lithium, clorgyline, imipramine, fluphenazine and constant darkness on the alpha-melanotropin content and circadian rhythm in rat brain.  Eur J Pharmacol. 1982;  85 1-7
  • 47 Olpe H R, Steinmann M W, Pozza M F, Brugger F, Schmutz M. Valproate enhances GABA-A mediated inhibition of locus coeruleus neurones in vitro.  Naunyn Schmiedebergs Arch Pharmacol. 1988;  338 655-657
  • 48 Paykel E S, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barocka A. Residual symptoms after partial remission: an important outcome in depression.  Psychol Med. 1995;  25 1171-1180
  • 49 Petraglia F, Bakalakis S, Facchinetti F, Volpe A, Muller E E, Genazzani A R. Effects of sodium valproate and diazepam on beta-endorphin, beta-lipotropin and cortisol secretion induced by hypoglycemic stress in humans.  Neuroendocrinology. 1986;  44 320-325
  • 50 Post R M. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.  Am J Psychiatry. 1992;  149 999-1010
  • 51 Rabe-Jablonska J, Szymanska A. Diurnal profile of melatonin secretion in the acute phase of major depression and in remission.  Med Sci Monit. 2001;  7 946-952
  • 52 Raoux N, Benoit O, Dantchev N, Denise P, Franc B, Allilaire J F. et al . Circadian pattern of motor activity in major depressed patients undergoing antidepressant therapy: relationship between actigraphic measures and clinical course.  Psychiatry Res. 1994;  52 85-98
  • 53 Ren M, Senatorov V V, Chen R W, Chuang D M. Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model.  Proc Natl Acad Sci USA. 2003;  100 6210-6215
  • 54 Reul J M, Stec I, Soder M, Holsboer F. Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system.  Endocrinology. 1993;  133 312-320
  • 55 Sands S A, Guerra V, Morilak D A. Changes in tyrosine hydroxylase mRNA expression in the rat locus coeruleus following acute or chronic treatment with valproic acid.  Neuropsychopharmacology. 2000;  22 27-35
  • 56 Scatton B, Serrano A, Nishikawa T. GABA mimetics decrease extracellular concentrations of 5-HIAA (as measured by in vivo voltammetry) in the dorsal raphe of the rat.  Brain Res. 1985;  341 372-376
  • 57 Scott J, Pope M. Cognitive styles in individuals with bipolar disorders.  Psychol Med. 2003;  33 1081-1088
  • 58 Scott J, Teasdale J D, Paykel E S, Johnson A L, Abbott R, Hayhurst H. et al . Effects of cognitive therapy on psychological symptoms and social functioning in residual depression.  Br J Psychiatry. 2000;  177 440-446
  • 59 Segal Z V, Gemar M, Williams S. Differential cognitive response to a mood challenge following successful cognitive therapy or pharmacotherapy for unipolar depression.  J Abnorm Psychol. 1999;  108 3-10
  • 60 Serretti A, Benedetti F, Mandelli L, Lorenzi C, Pirovano A, Colombo C. et al . Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism.  Am J Med Genet. 2003;  121 35-38
  • 61 Sheline Y I, Gado M H, Kraemer H C. Untreated depression and hippocampal volume loss.  Am J Psychiatry. 2003;  160 1516-1518
  • 62 Sheline Y I, Sanghavi M, Mintun M A, Gado M H. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression.  J Neurosci. 1999;  19 5034-5043
  • 63 Simons A D, Murphy G E, Levine J L, Wetzel R D. Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year.  Arch Gen Psychiatry. 1986;  43 43-48
  • 64 Soares J C, Dippold C S, Mallinger A G. Platelet membrane phosphatidylinositol-4,5-bisphosphate alterations in bipolar disorder-evidence from a single case study.  Psychiatry Res. 1997;  69 197-202
  • 65 Solomon D A, Ristow W R, Keller M B, Kane J M, Gelenberg A J, Rosenbaum J F. et al . Serum lithium levels and psychosocial function in patients with bipolar I disorder.  Am J Psychiatry. 1996;  153 1301-1307
  • 66 Southam E, Kirkby D, Higgins G A, Hagan R M. Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxytryptamine uptake in rats.  Eur J Pharmacol. 1998;  358 19-24
  • 67 Stout S C, Owens M J, Lindsey K P, Knight D L, Nemeroff C B. Effects of sodium valproate on corticotropin-releasing factor systems in rat brain.  Neuropsychopharmacology. 2001;  24 624-631
  • 68 Strakowski S M, DelBello M P, Zimmerman M E, Getz G E, Mills N P, Ret J. et al . Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder.  Am J Psychiatry. 2002;  159 1841-1847
  • 69 Teasdale J D, Moore R G, Hayhurst H, Pope M, Williams S, Segal Z V. Metacognitive awareness and prevention of relapse in depression: empirical evidence.  J Consult Clin Psychol. 2002;  70 275-287
  • 70 Tse W S, Bond A J. Reboxetine promotes social bonding in healthy volunteers.  J Psychopharmacol. 2003;  17 189-195
  • 71 Wadenberg M L, Hillegaart V. Stimulation of median, but not dorsal, raphe 5-HT1A autoreceptors by the local application of 8-OH-DPAT reverses raclopride-induced catalepsy in the rat.  Neuropharmacology. 1995;  34 495-499
  • 72 Welsh D K, Moore-Ede M C. Lithium lengthens circadian period in a diurnal primate, Saimiri sciureus.  Biol Psychiatry. 1990;  28 117-126
  • 73 Widerlov E, Ekman R, Jensen L, Borglund L, Nyman K. Arginine vasopressin, but not corticotropin releasing factor, is a potent stimulator of adrenocorticotropic hormone following electroconvulsive treatment.  J Neural Transm. 1989;  75 101-109
  • 74 Williams R S, Cheng L, Mudge A W, Harwood A J. A common mechanism of action for three mood-stabilizing drugs.  Nature. 2002;  417 292-295
  • 75 Zhou J N, Riemersma R F, Unmehopa U A, Hoogendijk W J, van Heerikhuize J J, Hofman M A. et al . Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression.  Arch Gen Psychiatry. 2001;  58 655-662
  • 76 Zobel A W, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M. Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression. A prospective study.  J Psychiatr Res. 2001;  35 83-94

Bruno Baumann, MD

Department of Psychiatry

Psychotherapy and Psychosomatic Medicine

Otto-von-Guericke-University of Magdeburg

Leipziger Strasse 44

39120 Magdeburg

Germany

Phone: +49 391 67 15019

Fax: +49 391 67 190367

Email: baumann@med.uni-magdeburg.de

    >