Prednisolone Suppression Test predicts response to intensive treatment7• Poor naturalistic prognosis1

•Tertiary treatment works2

-acutely-long term-reduced local service use-reduced self harm

• Clinical predictors of response-Maudsley Staging Model3

•Predictors of relapse-Social support-Residual symptoms4

-Carer stress5

•Biological disturbance-HPA axis overdrive6

1. Fekadu et al, J Aff Disord 2009; 2. Wooderson et al, J Aff Disord 2011; 3. Fekadu et al, J Clin Psychiatry 2009; 4. Fekadu et al, Can J Psychiatry 2011; 5. Rane et al, Psychol Med, 2011; 6. Markopoulou et al, Psychoneuroendocrinol, 2009; 7. Juruena et al, Br J Psychiatry 2009

-Consistent findings of: - low basal cortisol- reduced cortisol reactivity- enhanced negative feedback control1

-Many factors interact to cause HPA change1

-Low cortisol contributes to symptoms1,2

1. Papadopoulos & Cleare, Nature Reviews: Endocrinol. 2011; 2. Cleare et al, Lancet, 1999; 3. Roberts et al, J Aff Disord, 2009; 4. Roberts et al, 2010, Psychol Med.

CBT can reverse these changes overall3

-But patients with lowest cortisol levels respond less well to CBT treatment4

-This may be a biological marker of a need for different or longer treatments

Salivary cortisol

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• Clinically can’t distinguish unipolar from bipolar depression• However, treatment approaches very different• Expansion of bipolarity spectrum – when to treat as unipolar?

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Cortisol reactivity distinguishes bipolar and unipolar depression1

1. Markopoulou et al, presented at ISAD 2012

• Antidepressants may work via glucocorticoid receptors• May be a rationale for lack of good efficacy of antidepressants in bipolar depression• Suggests alternative approaches