Psychological Medicine

Original Articles

Emotional reactivity in chronic schizophrenia: structural and functional brain correlates and the influence of adverse childhood experiences

F. Benedettia1a2 c1, D. Radaellia1a2, S. Polettia1a2a3, A. Falinia2a4, R. Cavallaroa1, S. Dallaspeziaa1a2, R. Riccabonia1a2, G. Scottia2a4 and E. Smeraldia1a2

a1 Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy

a2 C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy

a3 Department of Pharmacological Sciences, Università degli Studi di Palermo, Italy

a4 Department of Neuroradiology, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy


Background Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression).

Method Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural responses to a face-matching paradigm, and regional grey matter (GM) volumes were studied at 3.0 T in the amygdala, hippocampus, anterior cingulated cortex (ACC) and prefrontal cortex (PFC). The severity of ACEs was assessed. Participants included 20 consecutively admitted in-patients affected by chronic undifferentiated schizophrenia, and 20 unrelated healthy volunteers from the general population.

Results Patients reported higher ACEs than controls. Worse ACEs proportionally led to decreasing responses in the amygdala and hippocampus, and to increasing responses in the PFC and ACC in all participants. Patients showed higher activations in the amygdala and hippocampus, and lower activations in the PFC and ACC. Higher ACEs were associated with higher GM volumes in the PFC and ACC, and schizophrenia was associated with GM reduction in all studied regions.

Conclusions Structural and functional brain correlates of emotional reactivity are influenced by both current chronic undifferentiated schizophrenia and the severity of past ACEs.

(Received November 17 2009)

(Revised April 16 2010)

(Accepted April 29 2010)

(Online publication June 09 2010)


c1 Address for correspondence: F. Benedetti, M.D., Istituto Scientifico Ospedale San Raffaele, Department of Clinical Neurosciences, San Raffaele Turro, Via Stamira d'Ancona 20, Milan, Italy. (Email: