Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder

Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting‐state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.

[1]  E. Walker,et al.  Chronic stress and stressful life events in the offspring of parents with bipolar disorder. , 2009, Journal of affective disorders.

[2]  S. Frangou.  Risk and resilience in bipolar disorder: rationale and design of the Vulnerability to Bipolar Disorders Study (VIBES). , 2009, Biochemical Society transactions.

[3]  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.

[4]  Kaustubh Supekar,et al.  Dynamic Reconfiguration of Structural and Functional Connectivity Across Core Neurocognitive Brain Networks with Development , 2011, The Journal of Neuroscience.

[5]  Thomas E. Nichols,et al.  Validating cluster size inference: random field and permutation methods , 2003, NeuroImage.

[6]  R. Salvador,et al.  Failure of de-activation in the medial frontal cortex in mania: evidence for default mode network dysfunction in the disorder , 2012, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[7]  Eduard Vieta,et al.  A systematic literature review of resting state network--functional MRI in bipolar disorder. , 2013, Journal of affective disorders.

[8]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[9]  R. Gibbons,et al.  Preliminary studies of the reliability and validity of the children's depression rating scale. , 1984, Journal of the American Academy of Child Psychiatry.

[10]  R. Davidson,et al.  Social influences on neuroplasticity: stress and interventions to promote well-being , 2012, Nature Neuroscience.

[11]  M. Phillips,et al.  Fronto-limbic function in unaffected offspring at familial risk for bipolar disorder during an emotional working memory paradigm , 2013, Developmental Cognitive Neuroscience.

[12]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[13]  R. McIntyre,et al.  Towards a multifactorial approach for prediction of bipolar disorder in at risk populations. , 2012, Journal of affective disorders.

[14]  R. Olvera,et al.  Family environment patterns in families with bipolar children. , 2008, Journal of affective disorders.

[15]  R. C. Young,et al.  A Rating Scale for Mania: Reliability, Validity and Sensitivity , 1978, British Journal of Psychiatry.

[16]  B. Frey,et al.  Early intervention in bipolar disorders: clinical, biochemical and neuroimaging imperatives. , 2009, Journal of affective disorders.

[17]  Lisa H. Lu,et al.  Altered affective, executive and sensorimotor resting state networks in patients with pediatric mania. , 2013, Journal of psychiatry & neuroscience : JPN.

[18]  Kaustubh Supekar,et al.  Developmental Maturation of Dynamic Causal Control Signals in Higher-Order Cognition: A Neurocognitive Network Model , 2012, PLoS Comput. Biol..

[19]  M. Phillips,et al.  Aberrant executive attention in unaffected youth at familial risk for mood disorders. , 2013, Journal of Affective Disorders.

[20]  L. Yao,et al.  Resting-state abnormal baseline brain activity in unipolar and bipolar depression , 2012, Neuroscience Letters.

[21]  J. Os,et al.  Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives , 2007, Psychological Medicine.

[22]  James Robert Brašić,et al.  A children's global assessment scale (CGAS). , 1983, Archives of general psychiatry.

[23]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[24]  Kevin Murphy,et al.  Resting-state fMRI confounds and cleanup , 2013, NeuroImage.

[25]  L. Covi,et al.  SCL-90: an outpatient psychiatric rating scale--preliminary report. , 1973, Psychopharmacology bulletin.

[26]  Xi-Nian Zuo,et al.  Fronto-Temporal Spontaneous Resting State Functional Connectivity in Pediatric Bipolar Disorder , 2010, Biological Psychiatry.

[27]  K. Sundet,et al.  PSYCHOMETRIC PROPERTIES OF A NORWEGIAN RESEARCH VERSION OF THE 'WECHSLER ABBREVIATED SCALE OF INTELLIGENCE' (WASI) , 2001 .

[28]  S. Strakowski,et al.  Family environment in families with versus families without parental bipolar disorder: a preliminary comparison study. , 2005, Bipolar disorders.

[29]  J. Parker,et al.  The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[30]  F. Castellanos,et al.  A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder , 2011, Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53.

[31]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[32]  K. Chang,et al.  Prevention of bipolar disorder in at-risk children: Theoretical assumptions and empirical foundations , 2008, Development and Psychopathology.

[33]  E. Leibenluft,et al.  Risk for bipolar disorder is associated with face-processing deficits across emotions. , 2008, Journal of the American Academy of Child and Adolescent Psychiatry.

[34]  N. Filippini,et al.  Group comparison of resting-state FMRI data using multi-subject ICA and dual regression , 2009, NeuroImage.

[35]  E. Bora,et al.  Meta-analysis of volumetric abnormalities in cortico-striatal-pallidal-thalamic circuits in major depressive disorder , 2011, Psychological Medicine.

[36]  A. Reiss,et al.  Reward processing in adolescents with bipolar I disorder. , 2013, Journal of the American Academy of Child and Adolescent Psychiatry.

[37]  Michael Breakspear,et al.  Reduced Inferior Frontal Gyrus Activation During Response Inhibition to Emotional Stimuli in Youth at High Risk of Bipolar Disorder , 2013, Biological Psychiatry.

[38]  A. Reiss,et al.  Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder. , 2012, Journal of the American Academy of Child and Adolescent Psychiatry.

[39]  M. Carskadon,et al.  A self-administered rating scale for pubertal development. , 1993, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[40]  D. Olson,et al.  FACES IV and the Circumplex Model: validation study. , 2011, Journal of marital and family therapy.

[41]  Yu-Te Wu,et al.  Classification of bipolar disorder using basal-ganglia-related functional connectivity in the resting state , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[42]  S. Faraone,et al.  Further evidence for robust familiality of pediatric bipolar I disorder: results from a very large controlled family study of pediatric bipolar I disorder and a meta-analysis. , 2012, The Journal of clinical psychiatry.

[43]  M. Leboyer,et al.  Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses. , 2011, Journal of affective disorders.

[44]  Stephen M. Smith,et al.  Probabilistic independent component analysis for functional magnetic resonance imaging , 2004, IEEE Transactions on Medical Imaging.

[45]  P. Lucassen,et al.  Early-life stress mediated modulation of adult neurogenesis and behavior , 2012, Behavioural Brain Research.

[46]  E. Leibenluft,et al.  Amygdala hyperactivation during face emotion processing in unaffected youth at risk for bipolar disorder. , 2012, Journal of the American Academy of Child and Adolescent Psychiatry.

[47]  Steven J. Stanton,et al.  Loss of Sustained Activity in the Ventromedial Prefrontal Cortex in Response to Repeated Stress in Individuals with Early-Life Emotional Abuse: Implications for Depression Vulnerability , 2013, Front. Psychol..

[48]  R. Murray,et al.  Genetic Liability for Bipolar Disorder Is Characterized by Excess Frontal Activation in Response to a Working Memory Task , 2008, Biological Psychiatry.

[49]  Alessandra M Passarotti,et al.  An fMRI study of the neural correlates of incidental versus directed emotion processing in pediatric bipolar disorder. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[50]  Katya Rubia,et al.  Dissociable functional connectivity changes during the Stroop task relating to risk, resilience and disease expression in bipolar disorder , 2011, NeuroImage.

[51]  H. F. Crovitz,et al.  A group-test for assessing hand- and eye-dominance. , 1962, The American journal of psychology.

[52]  Steven H. Jones,et al.  A review of potential cognitive and environmental risk markers in children of bipolar parents. , 2008, Clinical psychology review.

[53]  Michael C. Stevens,et al.  Reduced Functional Connectivity of Prefrontal Regions and Amygdala Within Affect and Working Memory Networks in Pediatric Bipolar Disorder , 2012, Brain Connect..

[54]  Q. Jiao,et al.  Altered Regional Homogeneity in Pediatric Bipolar Disorder during Manic State: A Resting-State fMRI Study , 2013, PloS one.

[55]  E. Youngstrom,et al.  An inexpensive family index of risk for mood issues improves identification of pediatric bipolar disorder. , 2013, Psychological assessment.

[56]  H. Nicolini,et al.  Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families. , 2010, Archives of general psychiatry.

[57]  J. Smoller,et al.  Family, twin, and adoption studies of bipolar disorder , 2003, American journal of medical genetics. Part C, Seminars in medical genetics.

[58]  K. Chang,et al.  Socio-emotional processing and functioning of youth at high risk for bipolar disorder. , 2013, Journal of affective disorders.

[59]  Zhen Zhou,et al.  Abnormal baseline brain activity in bipolar depression: A resting state functional magnetic resonance imaging study , 2012, Psychiatry Research: Neuroimaging.

[60]  M. Greicius,et al.  Decoding subject-driven cognitive states with whole-brain connectivity patterns. , 2012, Cerebral cortex.

[61]  Li Yao,et al.  Regional Homogeneity within the Default Mode Network in Bipolar Depression: A Resting-State Functional Magnetic Resonance Imaging Study , 2012, PloS one.

[62]  Michael W. Cole,et al.  Amygdala connectivity differs among chronic, early course, and individuals at risk for developing schizophrenia. , 2014, Schizophrenia bulletin.

[63]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[64]  E. Bramon,et al.  Executive functioning in familial bipolar I disorder patients and their unaffected relatives. , 2011, Bipolar disorders.

[65]  E. Walker,et al.  Sensitivity to stress among the offspring of parents with bipolar disorder: a study of daytime cortisol levels , 2011, Psychological Medicine.

[66]  V. Menon,et al.  Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation. , 2004, Archives of general psychiatry.

[67]  Liang Zhan,et al.  Impaired Inter-Hemispheric Integration in Bipolar Disorder Revealed with Brain Network Analyses , 2013, Biological Psychiatry.

[68]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[69]  M. Phillips,et al.  Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression , 2012, Bipolar disorders.

[70]  Todd A. Hare,et al.  Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents , 2011, Journal of Cognitive Neuroscience.

[71]  Almila Erol,et al.  Ventral prefrontal executive function impairment as a potential endophenotypic marker for bipolar disorder , 2014, Nordic journal of psychiatry.

[72]  D. Kupfer,et al.  Psychosocial functioning in offspring of parents with bipolar disorder. , 2011, Journal of affective disorders.

[73]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[74]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[75]  M Williams,et al.  Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[76]  Mario Dzemidzic,et al.  Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression , 2009, Psychiatry Research: Neuroimaging.

[77]  T. Ketter,et al.  Family environment of children and adolescents with bipolar parents. , 2001, Bipolar disorders.

[78]  Marguerite Schneider,et al.  Neuroprogression in bipolar disorder , 2012, Bipolar disorders.

[79]  C. Kilts,et al.  Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress , 2012, Psychological Medicine.

[80]  M. Stevens,et al.  Pharmacotherapy impacts functional connectivity among affective circuits during response inhibition in pediatric mania , 2012, Behavioural Brain Research.

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

[82]  B. Birmaher,et al.  Phenomenology, longitudinal course, and outcome of children and adolescents with bipolar spectrum disorders. , 2009, Child and adolescent psychiatric clinics of North America.

[83]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Michelle Hampson,et al.  Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder , 2010, Psychiatry Research: Neuroimaging.

[85]  K. Chang.  Course and impact of bipolar disorder in young patients. , 2010, The Journal of clinical psychiatry.

[86]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[87]  E. Leibenluft,et al.  Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[88]  J. Sweeney,et al.  Enhanced prefrontal function with pharmacotherapy on a response inhibition task in adolescent bipolar disorder. , 2010, The Journal of clinical psychiatry.

[89]  M. Alda,et al.  Brain Structural Signature of Familial Predisposition for Bipolar Disorder: Replicable Evidence For Involvement of the Right Inferior Frontal Gyrus , 2013, Biological Psychiatry.

[90]  Melissa J. Green,et al.  The cognitive and neurophysiological basis of emotion dysregulation in bipolar disorder. , 2007, Journal of affective disorders.

[91]  M. Brammer,et al.  Progressive increase of frontostriatal brain activation from childhood to adulthood during event‐related tasks of cognitive control , 2006, Human brain mapping.

[92]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[93]  E. Leibenluft,et al.  Neural correlates of cognitive flexibility in children at risk for bipolar disorder. , 2012, Journal of psychiatric research.

[94]  S. Frangou.  Brain structural and functional correlates of resilience to Bipolar Disorder , 2011, Front. Hum. Neurosci..

[95]  V. Calhoun,et al.  Differences in Resting-State Functional Magnetic Resonance Imaging Functional Network Connectivity Between Schizophrenia and Psychotic Bipolar Probands and Their Unaffected First-Degree Relatives , 2012, Biological Psychiatry.

[96]  Margaret S. Brumbaugh,et al.  Trait impulsivity as an endophenotype for bipolar I disorder. , 2012, Bipolar disorders.