{
  "abstract": "Background Despite the impact of depression in multiple sclerosis (MS), the neurobiological mechanisms underlying its pathogenesis are still poorly understood. Disrupted functional connectivity (FC) within the reward circuit has been observed in major depressive disorder (MDD), highlighting its essential role in the neurobiology of depression. Here, we hypothesised that an analogous dysconnectivity may underpin depression in MS.Methods The present study aimed to investigate FC of key nodes of the reward circuit (nucleus accumbens, NAcc and ventral tegmental area, VTA) in MS patients with depression (MS-D; n=30, 22 females), characterising differences with MS patients without depression (MS-nD; n=30, 17 females) and MDD patients without MS (n=30, 23 females). Furthermore, dynamic causal modelling (DCM) was applied to resting-state functional magnetic resonance imaging (fMRI) data to characterise effective connectivity (EC), which refers to the causal influences of brain regions involved in the circuit.Results MS-D group showed reduced FC compared with both MS-nD and MDD, suggesting that the association of depression with MS may reflect dysfunction of the reward circuit. The DCM analysis showed inhibitory self-connections, a negative modulation of VTA in MS-D>MS-nD, a negative modulation between VTA, NAcc and the right amygdala as an effect of having depression and no EC differences for MS-D>MDD.Conclusions The present connectivity study revealed promising results for understanding the pathophysiology of depression in MS. A combined FC-EC investigation of the reward circuit may represent a potential non-invasive in vivo MRI biomarker for understanding the onset of core depressive symptoms, supporting the development of effective and personalised therapies.",
  "authors": [
    {
      "affiliations": [
        "IRCCS Ospedale Policlinico San Martino, Genoa, Italy"
      ],
      "name": "Giada Lombardi"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Elisa Leveraro"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Emilio Cipriano"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Tommaso Sirito"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Maria Cellerino"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Lorenza Nasone"
    },
    {
      "affiliations": [
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Gianluca Serafini"
    },
    {
      "affiliations": [
        "Department of Mental Health and Addictions, ASL 3 Genovese, Genoa, Liguria, Italy"
      ],
      "name": "Lucio Ghio"
    },
    {
      "affiliations": [
        "IRCCS Ospedale Policlinico San Martino, Genoa, Italy",
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Andrea Escelsior"
    },
    {
      "affiliations": [
        "IRCCS Ospedale Policlinico San Martino, Genoa, Italy",
        "Università degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Liguria, Italy"
      ],
      "name": "Matilde Inglese"
    }
  ],
  "title": "Functional and effective connectivity disruptions of the dopaminergic reward circuit in multiple sclerosis patients with depression",
  "uid": "d976adbb-419f-54e4-a2e5-d1d8271b121b"
}