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A Functional Magnetic Resonance Imaging Study of Moral Valence Decision in Bipolar Depression

Francesco Benedetti, MD; Alessandro Bernasconi, MD; Valeria Blasi, MD; Marcello Cadioli, PhD; Cristina Colombo, MD; Andrea Falini, MD; Cristina Lorenzi, PhD; Daniele Radaelli, PhD; Giuseppe Scotti, MD; Enrico Smeraldi, MD

Arch Gen Psychiatry. 2007;64(2):179-187.

Context  Total sleep deprivation combined with light therapy causes rapid amelioration of bipolar depression. A polymorphism in the promoter for the serotonin transporter influences both antidepressant response and the structure and function of specific brain areas.

Objective  To determine whether antidepressant therapy or the genotype of the serotonin transporter influence the pattern of neural response to a task targeting the depressive biases in information processing (moral valence decision).

Design  Before-and-after trial studying the biologic correlates of response to treatment.

Setting  University hospital.

Patients  Twenty inpatients with bipolar depression.

Intervention  Repeated total sleep deprivation combined with light therapy for 1 week.

Main Outcome Measures  Brain blood oxygen level–dependent functional magnetic resonance imaging using a 3.0-T scanner before and after treatment. Self-ratings and observer ratings of mood (visual analog scale 3 times daily and Hamilton Depression Rating Scale) before and after treatment.

Results  We found significant interactions of treatment (before and after), response to treatment (Hamilton Depression Rating Scale score <8), and moral valence of the stimuli (positive or negative) in the anterior cingulate cortex, dorsolateral prefrontal cortex, insula, and parietal cortex. In these areas, responders changed their blood oxygen level–dependent responses to emotional stimuli in a pattern opposite of that in nonresponders. Genotype of the promoter for the serotonin transporter predicted response to treatment and influenced baseline neural responses in the anterior cingulate cortex and the dorsolateral prefrontal cortex.

Conclusion  Multiple factors that affect or are affected at the individual level by major depressive episodes in the course of bipolar disorder significantly interact in influencing brain cortical activity in specific areas.

Author Affiliations: Departments of Neuropsychiatric Sciences (Drs Benedetti, Bernasconi, Colombo, Lorenzi, Radaelli, and Smeraldi) and Neuroradiology (Drs Blasi, Cadioli, Falini, and Scotti), San Raffaele Scientific Institute; and Centro di Eccellenza Risonanza Magnetica ad Alto Campo (Drs Benedetti, Bernasconi, Blasi, Colombo, Falini, Radaelli, Scotti, and Smeraldi), University Vita-Salute San Raffaele, Milan, Italy; Dottorato in Neuroscienze e Disturbi del Comportamento, Dipartimento di Scienze Farmacologiche, Università degli Studi di Palermo, Palermo, Italy (Dr Radaelli); and Philips Medical Systems, Eindhoven, the Netherlands (Dr Cadioli).