Matthew P Hyett1, Michael J Breakspear2, Karl J Friston3, Christine C Guo4, Gordon B Parker5. 1. School of Psychiatry, University of New South Wales, New South Wales, Australia2Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia3QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. 2. School of Psychiatry, University of New South Wales, New South Wales, Australia2Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia3QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia4Metro North Menta. 3. Wellcome Trust Centre for Neuroimaging, University College London, London, England. 4. QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. 5. School of Psychiatry, University of New South Wales, New South Wales, Australia2Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Abstract
IMPORTANCE: Patients with melancholia report a distinct and intrusive dysphoric state during internally generated thought. Melancholia has long been considered to have a strong biological component, but evidence for its specific neurobiological origins is limited. The distinct neurocognitive, psychomotor, and mood disturbances observed in melancholia do, however, suggest aberrant coordination of frontal-subcortical circuitry, which may best be captured through analysis of complex brain networks. OBJECTIVE: To investigate the effective connectivity between spontaneous (resting-state) brain networks in melancholia, focusing on networks underlying attention and interoception. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, observational, resting-state functional magnetic resonance imaging study of 16 participants with melancholia, 16 with nonmelancholic depression, and 16 individuals serving as controls at a hospital-based research institute between August 30, 2010, and June 27, 2012. We identified 5 canonical resting-state networks (default mode, executive control, left and right frontoparietal attention, and bilateral anterior insula) and inferred spontaneous interactions among these networks using dynamic causal modeling. MAIN OUTCOMES AND MEASURES: Graph theoretic measures of brain connectivity, namely, in-degree and out-degree of each network and edge connectivity, between regions composed our principal between-group contrasts. RESULTS: Melancholia was characterized by a pervasive disconnection involving anterior insula and attentional networks compared with participants in the control (Mann-Whitney, 189.00; z = 2.38; P = .02) and nonmelancholic depressive (Mann-Whitney, 203.00; z = 2.93; P = .004) groups. Decreased effective connectivity between the right frontoparietal and insula networks was present in participants with melancholic depression compared with those with nonmelancholic depression (χ2 = 8.13; P = .004). Reduced effective connectivity between the insula and executive networks was found in individuals with melancholia compared with healthy controls (χ2 = 8.96; P = .003). CONCLUSIONS AND RELEVANCE: We observed reduced effective connectivity in resting-state functional magnetic resonance imaging between key networks involved in attention and interoception in melancholia. We propose that these abnormalities underlie the impoverished variety and affective quality of internally generated thought in this disorder.
IMPORTANCE: Patients with melancholia report a distinct and intrusive dysphoric state during internally generated thought. Melancholia has long been considered to have a strong biological component, but evidence for its specific neurobiological origins is limited. The distinct neurocognitive, psychomotor, and mood disturbances observed in melancholia do, however, suggest aberrant coordination of frontal-subcortical circuitry, which may best be captured through analysis of complex brain networks. OBJECTIVE: To investigate the effective connectivity between spontaneous (resting-state) brain networks in melancholia, focusing on networks underlying attention and interoception. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, observational, resting-state functional magnetic resonance imaging study of 16 participants with melancholia, 16 with nonmelancholic depression, and 16 individuals serving as controls at a hospital-based research institute between August 30, 2010, and June 27, 2012. We identified 5 canonical resting-state networks (default mode, executive control, left and right frontoparietal attention, and bilateral anterior insula) and inferred spontaneous interactions among these networks using dynamic causal modeling. MAIN OUTCOMES AND MEASURES: Graph theoretic measures of brain connectivity, namely, in-degree and out-degree of each network and edge connectivity, between regions composed our principal between-group contrasts. RESULTS:Melancholia was characterized by a pervasive disconnection involving anterior insula and attentional networks compared with participants in the control (Mann-Whitney, 189.00; z = 2.38; P = .02) and nonmelancholic depressive (Mann-Whitney, 203.00; z = 2.93; P = .004) groups. Decreased effective connectivity between the right frontoparietal and insula networks was present in participants with melancholic depression compared with those with nonmelancholic depression (χ2 = 8.13; P = .004). Reduced effective connectivity between the insula and executive networks was found in individuals with melancholia compared with healthy controls (χ2 = 8.96; P = .003). CONCLUSIONS AND RELEVANCE: We observed reduced effective connectivity in resting-state functional magnetic resonance imaging between key networks involved in attention and interoception in melancholia. We propose that these abnormalities underlie the impoverished variety and affective quality of internally generated thought in this disorder.
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