Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Poor task persistence is often observed among depressed individuals, and may be associated with some of the same frontal regions that are involved in depression. The current study explored the association between white-matter lesion volume in prefrontal cortex and noncompletion rates on a complex neurocognitive task among older adults in a treatment study for depression. Older adults in treatment for depression (n=83) and nondepressed (n=47) elders were administered the Stockings of Cambridge subtest (SoC) of the Cambridge Automated Neuropsychological Testing Battery (CANTAB) and completed a brain magnetic resonance imaging scan as part of an ongoing research study. Noncompletion of the SoC occurred in approximately 19% of depressed participants (16/83) and only 2% of nondepressed participants (1/47), which was statistically significant. In multivariate models, failure to complete the SoC was consistently and significantly associated with greater volume of white matter lesions in the anterior-most region of prefrontal cortex, particularly in the left hemisphere, and with greater age. Although SoC completion was not significantly associated with depression severity, noncompletion rates were significantly higher among unremitted individuals and those with comorbid anxiety at study entry. The inability to initiate behavior sufficient to sustain a complex neurocognitive task is a characteristic of geriatric depression which may be associated with integrity of left-prefrontal regions. Future research should investigate whether task impersistence is a construct that generalizes to other neurocognitive tasks, and if it is associated with other adverse outcomes in geriatric depression related to cerebrovascular pathology, such as poor treatment response.

[1]  P. Maruff,et al.  Neuropsychological function in young patients with unipolar major depression , 1997, Psychological Medicine.

[2]  A. Mortimer,et al.  Stability of set-shifting and planning abilities in patients with schizophrenia , 2004, Psychiatry Research.

[3]  K. Krishnan,et al.  Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression , 2004, Biological Psychiatry.

[4]  George S Alexopoulos,et al.  Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. , 2002, The American journal of psychiatry.

[5]  K. Krishnan,et al.  Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects , 2002, Psychiatry Research: Neuroimaging.

[6]  G. Alexopoulos,et al.  Executive dysfunction and disability in elderly patients with major depression. , 2001, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[7]  Warren D Taylor,et al.  White matter hyperintensity progression and late-life depression outcomes. , 2003, Archives of general psychiatry.

[8]  Y. Sheline,et al.  White matter hyperintensities and gray matter lesions in physically healthy depressed subjects. , 1999, The American journal of psychiatry.

[9]  P. Rabbitt,et al.  A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: Implications for theories of executive functioning and cognitive aging , 1998, Journal of the International Neuropsychological Society.

[10]  John L Bradshaw,et al.  Frontostriatal deficits in unipolar major depression , 1998, Brain Research Bulletin.

[11]  D. Pizzagalli,et al.  Toward an objective characterization of an anhedonic phenotype: A signal-detection approach , 2005, Biological Psychiatry.

[12]  K. Gersing,et al.  Methodology and Preliminary Results From the Neurocognitive Outcomes of Depression in the Elderly Study , 2004, Journal of geriatric psychiatry and neurology.

[13]  F. Reischies Pattern of Disturbance of Different Ventral Frontal Functions in Organic Depression , 1999, Annals of the New York Academy of Sciences.

[14]  A. Szegedi,et al.  Moderate and severe depression. Gradations for the Montgomery-Asberg Depression Rating Scale. , 2000, Journal of affective disorders.

[15]  T. Shallice Specific impairments of planning. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[16]  C. Naranjo,et al.  The role of the brain reward system in depression , 2001, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[17]  T. Robbins,et al.  Abnormal response to negative feedback in unipolar depression: evidence for a diagnosis specific impairment , 1997, Journal of neurology, neurosurgery, and psychiatry.

[18]  I. de Koning,et al.  Frontotemporal dementia and neuropsychology: the value of missing values , 2000, Journal of neurology, neurosurgery, and psychiatry.

[19]  G. Alexopoulos,et al.  Executive dysfunction in geriatric depression. , 2002, The American journal of psychiatry.

[20]  Po See Chen,et al.  White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study , 2006, International Psychogeriatrics.

[21]  K. Krishnan,et al.  The Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach. , 2002, Psychopharmacology bulletin.

[22]  James R. MacFall,et al.  Greater MRI lesion volumes in elderly depressed subjects than in control subjects , 2005, Psychiatry Research: Neuroimaging.

[23]  E. Rolls The orbitofrontal cortex and reward. , 2000, Cerebral cortex.

[24]  James M Provenzale,et al.  Subcortical white matter lesions and functional impairment in geriatric depression , 2002, Depression and anxiety.

[25]  G. Alexopoulos,et al.  Executive dysfunction and long-term outcomes of geriatric depression. , 2000, Archives of general psychiatry.

[26]  Sharlene D. Newman,et al.  Frontal and parietal participation in problem solving in the Tower of London: fMRI and computational modeling of planning and high-level perception , 2003, Neuropsychologia.

[27]  G. Dawson,et al.  Performance on Cambridge Neuropsychological Test Automated Battery Subtests Sensitive to Frontal Lobe Function in People with Autistic Disorder: Evidence from the Collaborative Programs of Excellence in Autism Network , 2004, Journal of autism and developmental disorders.

[28]  C. Frith,et al.  Prefrontal dysfunction in depressed patients performing a complex planning task: a study using positron emission tomography , 1997, Psychological Medicine.

[29]  R. Dolan,et al.  Neural systems engaged by planning: a PET study of the Tower of London task , 1996, Neuropsychologia.

[30]  G. Alexopoulos,et al.  Prefrontal dysfunction and treatment response in geriatric depression. , 1999, Archives of general psychiatry.

[31]  D. Tranel,et al.  Acquired Personality Disturbances Associated With Bilateral Damage to the Ventromedial Prefrontal Region , 2000, Developmental neuropsychology.

[32]  G. Shulman,et al.  Persistence and brain circuitry , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[33]  B. Sahakian,et al.  Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed , 1996, Psychological Medicine.

[34]  R Valabrègue,et al.  Individual differences in prefrontal cortical activation on the Tower of London planning task: implication for effortful processing , 2003, The European journal of neuroscience.

[35]  M Ashtari,et al.  Neuropsychological functioning and MRI signal hyperintensities in geriatric depression. , 1999, The American journal of psychiatry.

[36]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[37]  André Vandierendonck,et al.  Blunted prefrontal perfusion in depressed patients performing the Tower of London task , 2005, Psychiatry Research: Neuroimaging.

[38]  Frederik Barkhof,et al.  Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of tower of london task , 2003, NeuroImage.

[39]  David J. Pittenger The two paradigms of persistence. , 2002, Genetic, social, and general psychology monographs.

[40]  G. Alexopoulos,et al.  Clinical presentation of the "depression-executive dysfunction syndrome" of late life. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.