Affective Disorders

CHAIR: Sagar V. Parikh Address: Toronto Western Hospital, Room 9M-329, 399 Bathurst St. Toronto, Ontario M5T 2S8, Canada    
Phone: 1 416 603 5734
E-mail: sagar.parikh@uhn.on.ca
CO-CHAIR: Cornelius Katona Address: University College London, Department of Mental Health Sciences, Gower Street, London WC1E 6BT, United Kingdom    
E-mail: c.katona@ucl.ac.uk
SECRETARY: Caroline Holebrook Address: International Society for Affective Disorders, Institute of Psychiatry, King’s College London, P. O. 72 De Crespigny Park, Denmark Hill, London SE5 8AF, United Kingdom    
Phone: 44 207 848 0295
Fax: 44 207 848 0298
E-mail: Caroline.Holebrook@iop.kcl.ac.uk, isad@isad.org.uk


>> Please click here to see the Section Members list.

What's new in Affective Disorders?

Writing this short review has been made much easier by virtue of CK's role as Editor in Chief (with Prof Hagop Akiskal) of the Journal of Affective Disorders which is now the Section's official journal. CK has also had the opportunity to edit (with Prof Greg Simon) the Affective Disorders component of Current Opinion in Psychiatry for the last three years.

The review draws heavily on the summaries provided in Current Opinion. Research in affective disorders, as indeed in psychiatry as a whole, can conveniently be classified into four main areas: phenomenology and classification, aetiology, comorbidity, and management. We will review some of the (considerable) advances in each of these areas in turn.


Can there really be anything new to say about the symptoms and signs of affective illness or how they should be subclassified? Surprisingly, the answer is an emphatic 'yes'. Our understanding of the chronic but (so we thought) relatively mild depressions known as dysthymia has, in particular, advanced considerably. Rihmer's (1999) review reveals how profound our misconceptions have been about the by no means mild disorders at the periphery of major depression. He argues that dysthymia is a primary mood disorder with a mainly biological rather than psychosocial or psychodynamic basis. Akiskal's work (Akiskal et al 1997) fundamentaly reformulates dysthymia as a chronic, fluctuating primary mood disorder. Most of the biological abnormalities previously described in major depression, including changes in P300 amplitude on EEG (Murthy et al 1997) and platelet MAO activity (Tripodianakis et al 1998) also occur in dysthymia. Equally important, it is now clear that dysthymia responds well to antidepressant pharmacotherapy (Thase 1998) which should be given at full dose.

At the other 'extreme' of depression there remains fruitful debate as to whether depression complicated by delusions deserves a separate subclassification. Serretti's group (Serretti et al 2000; Lattuada et al 1999) found that patients with delusions had significantly more 'core' depressive symptomatology but responded similarly to treatment. These findings are in keeping with those of Muller et al (1999) in Germany. It is unsurprising, therefore, that newer antipsychotics alone are inadequate treatment for mood congruent delusions ((Muller-Siecheneder et al 1998). More surprising perhaps is the finding that SSRIs may be particularly effective in patients with delusional depression (Zanardi et al 2000).


Biological markers of depression remain a fruitful area of study. Platelet marker studies of the 5HT system remain inconclusive, though the study of prepubertal children by Pfeffer et al (1998) add further weight to the notion that platelet serotonin measures may be abnormal in patients with marked suicidal ideas. Single Photon Emission Tomography (SPET) has enabled serotonin function to be studied directly in living human brain, thus avoiding many of the problems confounding previous work on peripheral 5HT markers or in post-mortem tissue. Malison et al (1998) used radio-iodinated citalopram to quantify serotonin transporter activity in depressed subjects before and after treatment and reported a reduction in uptake sites in the brain stem of depressed patients which normalised with treatment. There is also emerging evidence for genetically determined variability in serotonin transport regulation (Lesch and Mossner 1998). Catecholamine studies have focused mainly on platelet adrenoceptors. Newly emerging adrenoceptor subtypes may be particularly important. Piletz et al (1996) for example suggest that the I1 subtype of imidazolamine receptor may be increased in the platelets of untreated depressed patients and normalise with treatment.

Immunological studies in depression continue to proliferate. Proinflammatory cytokines rise in depression and normalise with treatment (Sluzewski et al 1995); interleukin-2 receptor mediated blastoformation on the other hand is suppressed in depressed patients ( Kanba et al 1998) but also normalises with treatment.

Neuroendocrine research in affective disorders continues to focus mainly on the hypothalamo-pituitary-adrenal system but the emphasis is increasingly on the 'top end'. More specific 'probes' for 5HT subtypes show promise: blunted growth hormone response to sumatriptan in depression (Cleare et al 1998) suggests a specific abnormality in 5HT1D receptors. Studies by Scott and Dinan (1998) suggest that vasopressin challenge tests may be a better probe than dexamethasone or CRF as a test for depression-specific abnormalities in HPA axis function. Dinan (2001) argues that prolactin release to 5HT agonists may be a better marker of aggressivity than of depression, citing the work of Correa et al (2000) on patients with a history of suicide attempts and that of Fava et al (2000) on patients with 'anger attacks'. He considers that the HPA axis remains a legitimate focus for biological research in depression (and bipolar disorder). HPA axis changes may predict first episodes or relapses and there is growing evidence that normalising HPA function is effective in refractory depression (Wolkowitz and Reus 1999). Dinan concludes by suggesting, tantalisingly, that a new generation of antidepressants may in future target the HPA axis rather than monoamines.

A recent review by Reid and Stewart (2001) attempts to draw together threads from molecular and physiological studies in animals as well as neuroendocrine and neuropsychological studies in man to suggest that the primary action of antidepressants may be to reverse the neurotoxic effects of stressors on individual neurotrophin mediated neuronal growth activity and on the plasticity of neural networks. In this innovative model (which, like Dinan's work, suggests a range of novel therapeutic targets beyond the monoamines, chronic depression is conceptualised as a neurodegenerative disorder which early and vigorous treatment of acute episodes might prevent.


Both detection and management of depression can be particularly problematic in the context of comorbid medical illness. Anhedonia, low positive affect and high physiological arousal may be useful pointers to the presence of depression in medical patients (Clark et al 1998). The main risk factors for depression in physically ill patients (apart from severity of the physical illness itself) are the same socio-demographic variables (social isolation, poverty, past history of depression) that predispose to depression in physically healthy people (Koenig 1997). In the specific context of post-stroke depression, there is increasing evidence that previous reports of increased risk of depression following left-sided lesions may have been misleading and secondary to differences in the effect of lesion location on the ability to express depressive symptoms verbally (Gainotti et al 1997). Treatment trials have concentrated on antidepressants and attest, generally, to their efficacy as well as to the superior safety profile of SSRIs (Roose et al 1998).

Depression in primary care is emerging as an important research area, and one which can also be conceptualised in terms of comorbidity. Araya (1999) suggests that such depression may usefully be conceptualised as a different illness to 'hospital' depression with, in particular, more fatigue but fewer psychological symptoms. Prospects for improved management of primary care depression are good however in the light of evidence that both antidepressants a range of relatively simple psychological techniques including problem-solving (Mynors-Wallis et al 2000) and brief cognitive therapy (Scott et al 1997) are effective. Brief psychotherapies have also been shown to be superior to 'usual treatment' in depressed primary care patients (Ward et al 2000). The superiority of structured treatments may be due in large part to improved adherence (Peveler et al 1999, Simon et al 2000). Future primary care research outcome studies will use more appropriate outcome measures and include economic evaluation.


Depression resistant to treatment is still a major clinical problem, and research into specific treatments for refractory depression remains continues to proliferate. O'Reardon et al (2000) point out that, now that SSRIs are increasingly used as 'first-line' treatment, strategies are now needed for managing lack of response to this group of drugs. Surprisingly, similar responses are reported to switching to another SSRI, switching to another class of antidepressant, and adding lithium (Nelson 1998, Thase et al 1998). Evidence for more novel approaches such as pindolol augmentation (Soler et al 1999) or buspirone (Landen et al 1998) is, unfortunately, much weaker.

Relapse prevention, both in unipolar and bipolar disorder remains a major challenge. In bipolar disorder, anticonvulsants are increasingly used though recent controlled studies suggest that lithium is as effective as valproate (Bowden et al 2000) and superior to carbamazepine (Moleman et al 2000). The efficacy of lithium in preventing recurrence in unipolar depression is confirmed by the metaanalysis of placebo-controlled and 'mirror-image' studies by Davis et al (1999) and by a recent controlled trial of continuation treatment with lithium in combination with antidepressants (Bauer et al 2000). The SSRI citalopram has recently been shown (in a randomised comparison with placebo) substantially to delay recurrence in patients with a history of recurrent depression whose acute illness responded to open-label treatment with citalopram (Hochstrasser et al 2001). Similar results have been reported for another SSRI, paroxetine (Franchini et al 1998). The synergistic effect of antidepressants and Interpersonal Psychotherapy, well documented in younger patients by the Pittsburgh group, has now been shown to be similar in preventing recurrence in older patients at high risk (Reynolds et al 1999).

This brief review indicates that research in affective disorders is varied and flourishing. A new research organisation, the International Society for Affective Disorders (ISAD), has just been launched and will hold its inaugural meeting in Taormina, Sicily in March 2002. ISAD will bring together researchers from different disciplines and facilitate the development of a rational research agenda in the field. Collaboration will also be facilitated through web-based discussion. Active researchers in the field are welcome to join ISAD - visit the website on www.isad.soton.ac.uk. Membership includes personal subscription to the Journal of Affective Disorders, which is now it's house journal as well as that of our Section.

References for this article

- Akiskal H. S., Judd L. L., Gillin J. C., Lemmi H. (1997) Subthreshold depressions: clinical and polysomnographic validation of dysthymic, residual and masked forms. J Affect Dis 45, 53-63

- Araya R. (1999) The management of depression in primary health care. Curr Opin Psychiatry 12, 103-107

- Bauer M. B., Kunz T., Berghofer D. et al (2000) Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression. Arch Gen Psychiatry 157, 1429-1435

- Bowden C. L., Calabrese J. R., McElroy S. L. et al (2000) A randomised, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Arch Gen Psychiatry 57, 481-489

- Clark D. A., Cook A., Snow D. (1998) Depression symptom differences in hospitalised, medically ill, depressed psychiatric inpatients and nonmedical controls. J Abnorm Psychol 107, 38-48

- Cleare A. J., Murray R. M., Sherwood R. A., O'Keane V. (1998) Abnormal 5Ht1D receptor function in major depression: a neuropharmacological challenge study using sumatriptan. Psychol Med 28, 295-300

- Correa H., Duval F., Mokrani M. et al (2000) Prolactin response to d-fenfluramine and suicidal behaviour in depressed patients. Psychiat Res 93, 189-199

- Davis J., Janicak P., Hogan D. (1999) Mood stabilisers in the prevention of recurrent affective disorders: a meta-analysis. Acta Psychiat Scand 100, 406-417

- Dinan T. G. (2001) Psychoneuroendocrinology of mood disorders. Curr Opin psychiatry 14, 51-55

- Fava M., Vuolo R. D., Wright E. C. et al (2000) Fenfluramine challenge in unipolar depression with and without anger attacks. Psychiat Res 94, 9-18

- Franchini L., Gasperini M., Perez J. et al (1998) Dose-response efficacy of paroxetine in preventing depressive recurrences: a randomised, double-blind study. J Clin psychiat 59, 229-232

- Gainotti G., Azzoni A., Gasparini F., Maca C., Razzano C. (1997) Relation of lesion location to verbal and nonverbal mood measures in stroke patients. Stroke 28, 2145-2149

- Hochstrasser B., Isaksen P. M., Koponen H. et al (2001) Prophylactic effect of citalopram in unipolar, recurrent depression. Placebo-controlled study of maintenance therapy. Br J Psychiatry 178, 304-310

- Kanba S., Manki H., Shintoni Y., Oho Y., Yagi G., Asai M. (1998) Aberrant interleukin-2 receptor mediated blastoformation of peripheral blood lymphocytes in severe major depression. Psychol Med 28, 481-484

- Koenig H. G. (1997) Differences in psychosocial and health correlates of major and minor depression in medically ill older adults. J Am Geriatr Soc 45, 1487-1495

- Landen M., Bjorling G., Agren H., Fahlen T. (1998) A randomised, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry 59, 664-668

- Lattuada E., Serretti A., Cusin C. et al (1999) Symptomatologic analysis of psychotic and non-psychotic depression. J Affect Disord 54, 183-187

- Lesch K. P., Mossner R. (1998) Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental and neurodegenerative disorders? Biol Psychiatry 44, 179-192

- Malison R. T., Price L. H., Berman R. et al (1998) Reduced serotonin transporter availability in major depression as measured by 123I-2beta-carbometoxy-4-iodophenyl tropane and single photon emission tomography. Biol psychiatry 44, 1090-1108

- Moleman P., Hartong E. G. T. M., Hoogduin CAL et al (2000) Lithium and carbamazepine in bipolar disorder. Acta Neuropsychiatrica 12, 120-131

- Muller M. J., Wentzel H., Szegedi A., Benkert O. (1999) Three dimensions of depression in acute psychotic disorder: a replication study. Comp Psychiatry 40, 449-457

- Muller-Siecheneder F., Muller M. J., Montgomery S. A., Zonday E. (1998) Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome. J Clin psychopharmacol 18, 111-120

- Murthy N. V. P. J., Gangadhar B. N., Janakiramiah N., Subbakrishna D. K. (1997) Normalisation of P300 amplitude following treatment in dysthymia. Biol Psychiatry 42, 740-743

- Mynors-Wallis L. M., Gath D. H., Day A., Baker F. (2000) Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ 320, 26-30

- Nelson J. C. (1998) Treatment of antidepressant non-responders: augmentation or switch? J Clin Psychiatry 59 (suppl 15) 35-41

- O'Reardon J. P., Brunswick D. J. , Amsterdam J. D. (2000) Treatment-resistant depression in the age of serotonin: evolving strategies. Curr Opin Psychiatry 13, 93-98

- Peveler R., George C., Kinmonth A. L., Campbell M., Thompson C. (1999) Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ 319, 311-314

- Pfeffer C. R., McBride P. A., Anderson G. M., Kakuma T., Festerheim L., Khait V. (1998) Peripheral serotonin measures in prepubertal psychiatric patients and normal children: associations with suicidal behaviour and its risk factors. Biol Psychiatry 44, 568-577

- Piletz J. E., Halaris A., Nelson J., Qu Y., Bari M. (1996) Platelet I1-imidazoline binding sites are elevated in depression but not generalised anxiety disorder. J psychiatry Res 30, 147-168

- Reid I. C. and Stewart C. A. (2001) How antidepressants work: new perspectives on the pathophysiology of depressive disorder. Br J psychiatry 178, 299-303

- Reynolds C. F., Frank E., Perel J. M. et al (1999) Nortriptyline and Interpersonal Psychotherapy as maintenance therapies for recurrent major depression: a randomised controlled trial in patients older than 59 years. JAMA 281, 39-45

- Rihmer Z. (1999) Dysthymic disorder: implications for diagnosis and treatment. Curr Opin Psychiatry 12, 69-75

- Roose S. P., Laghrissi-Thode F., Kennedy J. S. et al (1998) Comparison of paroxetine and nortriptyline in depressed patients with ischaemic heart disease. JAMA 279, 287-291

- Scott L., Dinan T. G. (1998) Vasopressin and the regulation of the hypothalamic-pituitary- adrenal axis function: implications for the pathophysiology of depression. Life Sci 62, 1985-1988

- Scott C., Tacchi M. J., Jones R., Scott J. (1997) Acute and one-year outcome of a randomised controlled trial of brief cognitive therapy for major depressive disorder in primary care. Br J Psychiatry 171, 131-134

- Serretti A., Lattuada E., Zanarchi R. et al (2000) Patterns of symptom improvement during antidepressant treatmenmt of delusional depression. Psychiatry Res 94, 185-190

- Simon G. E., Von Korff M., Rutter C., Wagner E. (2000) randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary care. BMJ 2000, 320, 526-527

- Sluzewski A., Rybakowski J. K., Laciak M., Mackiewicz A., Sobieska M., Wiktorowicz K. (1995) Interleukin 6 levels in depressed patients before and after treatment. Ann NY Acad Sci 762, 774-777

- Soler P. V., Puigdemont D., Alvarez E., Artigas F. (1999) A double-blind, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Arch gen psychiatry 56, 375-379

- Thase M. E. (1998) Antidepressant treatment of dysthymia and related chronic depressions. Curr Opin Psychiatry 11, 77-83

- Thase M. E., Howland R. H., Friedman E. S. (1998) Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry 59 (suppl 15) 5-15

- Tripodianakis J., Markianos M., Sarantidis D., Spyroupoulou G., Taktikou V., Bistolaki E. (1998) Platelet MAO activity in patients with dysthymic disorder. Psychiatry Res 78, 173-178

- Ward E., King M., Lloyd M. et al (2000) Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I: clinical effectiveness. BMJ 321, 1383-1388

- Wolkowitz O. M., Reus V. I. (1999) Treatment of depression with antiglucocorticoid drugs. Psychosomat Med 61, 698-711

- Zanardi R., Franchini L., Serretti A. et al (2000). Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study. J Clin Psychiatry 61, 26-29

« Back
Send this to a colleague