Abnormal spontaneous neural activity in the anterior insular and anterior cingulate cortices in anxious depression

OBJECTIVE Anxious depression is a distinct clinical subtype of major depressive disorder (MDD) characterized by palpitations, somatic complaints, altered interoceptive awareness, high risk of suicide, and poor response to pharmacotherapy. However, the neural mechanisms of anxious depression are still not well understood. In this study we investigated changes in neural oscillation during the resting-state of patients with anxious depression by measuring differences in the amplitude of low-frequency fluctuation (ALFF). METHODS Resting-state functional magnetic resonance imaging was acquired in 31 patients with anxious depression, 18 patients with remitted depression, as well as 68 gender- and age-matched healthy participants. We compared the differences both in the ALFF and fractional ALFF (fALFF) among the three groups. We also examined the correlation between the ALFF/fALFF and the severity of anxiety as well as depression. RESULTS Anxious depression patients showed increased ALFF/fALFF in the right dorsal anterior insular cortex and decreased ALFF/fALFF in the bilateral lingual gyrus relative to remitted depression patients and healthy controls. The increased ALFF in the dorsal anterior insula was also positively correlated with stronger anxiety in the anxious depression group. Anxious depression patients also displayed increased fALFF in the right ventral anterior cingulate cortex (ACC) compared to remitted depression patients and healthy controls. CONCLUSIONS Our results suggest that alterations of the cortico-limbic networks, including the right dorsal anterior insula and right ventral ACC, may play a critical role in the physiopathology of anxious depression.

[1]  D. Ionescu,et al.  Defining anxious depression: a review of the literature , 2013, CNS Spectrums.

[2]  Chaozhe Zhu,et al.  An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: Fractional ALFF , 2008, Journal of Neuroscience Methods.

[3]  Karl J. Friston,et al.  Spontaneous neuronal activity predicts intersubject variations in executive control of attention , 2014, Neuroscience.

[4]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[5]  Yong He,et al.  Spatial patterns of intrinsic brain activity in mild cognitive impairment and alzheimer's disease: A resting‐state functional MRI study , 2011, Human brain mapping.

[6]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[7]  Yong He,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. , 2007, Brain & development.

[8]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[9]  D. Ionescu,et al.  NEUROBIOLOGY OF ANXIOUS DEPRESSION: A REVIEW , 2013, Depression and anxiety.

[10]  Melissa R. Weiner,et al.  INSULA AND ANTERIOR CINGULATE GABA LEVELS IN POSTTRAUMATIC STRESS DISORDER: PRELIMINARY FINDINGS USING MAGNETIC RESONANCE SPECTROSCOPY , 2014, Depression and anxiety.

[11]  Tomio Inoue,et al.  Anterior cingulate cortex volume reduction in patients with panic disorder , 2008, Psychiatry and clinical neurosciences.

[12]  Xin Ma,et al.  Difference in amplitude of low-frequency fluctuation between currently depressed and remitted females with major depressive disorder , 2013, Brain Research.

[13]  Laura B. Bragdon,et al.  Treating anxious depression using repetitive transcranial magnetic stimulation. , 2013, Journal of affective disorders.

[14]  P. Roland,et al.  Estimation of the Probabilities of 3D Clusters in Functional Brain Images , 1998, NeuroImage.

[15]  L. Derogatis,et al.  The Brief Symptom Inventory: an introductory report , 1983, Psychological Medicine.

[16]  Sarah Eichmann,et al.  Fourier Series And Orthogonal Functions , 2016 .

[17]  Jerzy Bodurka,et al.  Major Depressive Disorder Is Associated With Abnormal Interoceptive Activity and Functional Connectivity in the Insula , 2014, Biological Psychiatry.

[18]  Xi-Nian Zuo,et al.  REST: A Toolkit for Resting-State Functional Magnetic Resonance Imaging Data Processing , 2011, PloS one.

[19]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[20]  M. First,et al.  Structured clinical interview for DSM-IV axis I disorders : SCID-I: clinical version : administration booklet , 1996 .

[21]  Cameron S Carter,et al.  Stimulus and response conflict processing during perceptual decision making , 2009, Cognitive, affective & behavioral neuroscience.

[22]  Naomi B. Pitskel,et al.  Three Systems of Insular Functional Connectivity Identified with Cluster Analysis , 2010, Cerebral cortex.

[23]  Marc Joliot,et al.  Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia , 2013, Schizophrenia Research.

[24]  Karl J. Friston,et al.  Anterior insular cortex and emotional awareness , 2013, The Journal of comparative neurology.

[25]  Peter Herscovitch,et al.  Neural Correlates of Rapid Antidepressant Response to Ketamine in Treatment-Resistant Unipolar Depression: A Preliminary Positron Emission Tomography Study , 2013, Biological Psychiatry.

[26]  A. Etkin,et al.  Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. , 2011, The American journal of psychiatry.

[27]  C. Reynolds,et al.  The default mode network in late-life anxious depression. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[28]  M. Bennett,et al.  Correlating anterior insula gray matter volume changes in young people with clinical and neurocognitive outcomes: an MRI study , 2012, BMC Psychiatry.

[29]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[30]  Maurizio Fava,et al.  Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. , 2008, The American journal of psychiatry.

[31]  M. Shad,et al.  Gray matter differences between healthy and depressed adolescents: a voxel-based morphometry study. , 2012, Journal of child and adolescent psychopharmacology.

[32]  C. Frith,et al.  Development and neurophysiology of mentalizing. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  G. Tollefson,et al.  Fluoxetine, placebo, and tricyclic antidepressants in major depression with and without anxious features. , 1994, The Journal of clinical psychiatry.

[34]  Peter F. Liddle,et al.  Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging , 2004, Psychiatry Research: Neuroimaging.

[35]  M. Mintun,et al.  Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus , 2010, Proceedings of the National Academy of Sciences.

[36]  Alex Martin,et al.  Semantic memory and the brain: structure and processes , 2001, Current Opinion in Neurobiology.

[37]  wen ling ma,et al.  Behavioural Brain Research , 2016 .

[38]  Bharat B. Biswal,et al.  The oscillating brain: Complex and reliable , 2010, NeuroImage.

[39]  R. Bagby,et al.  Anxious and nonanxious depression. , 1993, The American journal of psychiatry.

[40]  Yufeng Zang,et al.  Standardizing the intrinsic brain: Towards robust measurement of inter-individual variation in 1000 functional connectomes , 2013, NeuroImage.

[41]  Byung-Joo Ham,et al.  Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: an optimized voxel-based morphometry study. , 2011, Journal of affective disorders.

[42]  Lutz Jäncke,et al.  Resting-State Functional and Structural Connectivity Within an Insula–Amygdala Route Specifically Index State and Trait Anxiety , 2013, Biological Psychiatry.

[43]  Colm G. Connolly,et al.  Resting-State Functional Connectivity of Subgenual Anterior Cingulate Cortex in Depressed Adolescents , 2013, Biological Psychiatry.

[44]  W. Drevets,et al.  The Subgenual Anterior Cingulate Cortex in Mood Disorders , 2008, CNS Spectrums.

[45]  Y. Su,et al.  Short-term effects of escitalopram on regional brain function in first-episode drug-naive patients with major depressive disorder assessed by resting-state functional magnetic resonance imaging , 2013, Psychological Medicine.

[46]  Chaozhe Zhu,et al.  Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI , 2007, NeuroImage.

[47]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[48]  W. Coryell,et al.  Follow-up and family study of anxious depression. , 1991, The American journal of psychiatry.

[49]  Xi-Nian Zuo,et al.  Amplitude of low-frequency oscillations in schizophrenia: A resting state fMRI study , 2010, Schizophrenia Research.

[50]  Li Yao,et al.  Resting-state brain activity in major depressive disorder patients and their siblings. , 2013, Journal of affective disorders.

[51]  Chaogan Yan,et al.  DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI , 2010, Front. Syst. Neurosci..

[52]  Sergi G. Costafreda,et al.  Predictive neural biomarkers of clinical response in depression: A meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies , 2013, Neurobiology of Disease.

[53]  M. Fava,et al.  The efficacy and tolerability of duloxetine in the treatment of anxious versus non-anxious depression: a post-hoc analysis of an open-label outpatient study. , 2007, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[54]  Yong-Ku Kim,et al.  The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment , 2010, Psychiatry investigation.

[55]  Y. Zang,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI , 2007, Brain and Development.

[56]  H. Meltzer Clinical development of atypical antipsychotics: research design and evaluation. Collaborative Working Group on Clinical Trial Evaluations. , 1998, The Journal of clinical psychiatry.

[57]  R. Lydiard,et al.  Anxious depression. , 1998, The Journal of clinical psychiatry.

[58]  S. Hashioka Antidepressants and neuroinflammation: Can antidepressants calm glial rage down? , 2011, Mini reviews in medicinal chemistry.