Prefrontal dysfunction and treatment response in geriatric depression.

BACKGROUND This study investigated the relationship of clinical, neuropsychological, and electrophysiological measures of prefrontal dysfunction with treatment response in elderly patients with major depression. METHODS Forty-nine depressed elderly subjects were studied before and after 6 weeks of adequate antidepressant treatment and compared with 22 psychiatrically normal controls. The psychomotor retardation item of the Hamilton Depression Rating Scale, the initiation/perseveration subscore of the Mattis Dementia Rating Scale, and the latency of the P300 auditory evoked potential were used as indices of prefrontal dysfunction. The intensity of antidepressant drug treatment was classified and monitored for a 6-week period. RESULTS Abnormal initiation/perseveration score, psychomotor retardation, and long P300 latency predicted 58% of the variance in change of depression scores from baseline to 6 weeks (F3= 20.1, P<.001). Depressed patients who remained symptomatic (n = 25) had more abnormal initiation/perseveration scores and longer P300 latency compared with depressed patients who achieved remission (n = 24) and control subjects. There were no differences between the last 2 groups. The association between psychomotor retardation, initiation/perseveration scores, P300 latency, and response to antidepressant treatment could not be explained by differences in demographic and clinical characteristics or treatment intensity between remitted and nonremitted depressed patients. CONCLUSIONS Prefrontal dysfunction was associated with poor or delayed antidepressant response in depressed elderly patients. This observation, if confirmed, may aid clinicians in identifying candidates for aggressive somatic therapies and for interventions offering structure of daily activities.

[1]  C. Coffey,et al.  White matter hyperintensity on magnetic resonance imaging: clinical and neuroanatomic correlates in the depressed elderly. , 1989, The Journal of neuropsychiatry and clinical neurosciences.

[2]  B L Miller,et al.  Cognition and white matter hyperintensities in older depressed patients. , 1996, The American journal of psychiatry.

[3]  M R Nuwer,et al.  IFCN recommended standards for long-latency auditory event-related potentials. Report of an IFCN committee. International Federation of Clinical Neurophysiology. , 1994, Electroencephalography and clinical neurophysiology.

[4]  M. Maes,et al.  Auditory event related potentials in major depression: prolonged P300 latency and increased P200 amplitude. , 1998, Journal of affective disorders.

[5]  Karl J. Friston,et al.  A PET study of word finding , 1991, Neuropsychologia.

[6]  G. Alexopoulos,et al.  'Vascular depression' hypothesis. , 1997, Archives of general psychiatry.

[7]  J. Hagman,et al.  Comparison of regional brain metabolism in bulimia nervosa and affective disorder assessed with positron emission tomography. , 1990, Journal of affective disorders.

[8]  K. Krishnan,et al.  Background factors and clinical symptoms of major depression with silent cerebral infarction. , 1994, Stroke.

[9]  M. Raichle,et al.  A functional anatomical study of unipolar depression , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  G. Alexopoulos,et al.  Clinically defined vascular depression. , 1997, The American journal of psychiatry.

[11]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[12]  F. Manes,et al.  Prevalence and clinical correlates of pathological affective display in Alzheimer's disease. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[13]  G. Alexopoulos,et al.  Recovery in geriatric depression. , 1996, Archives of general psychiatry.

[14]  S. Petersen,et al.  Changes in brain activity during motor learning measured with PET: effects of hand of performance and practice. , 1998, Journal of neurophysiology.

[15]  D. Benson,et al.  Subcortical Dementia: Review of an Emerging Concept , 1984 .

[16]  H. Mayberg,et al.  Frontal lobe dysfunction in secondary depression. , 1994, The Journal of neuropsychiatry and clinical neurosciences.

[17]  G. Alexopoulos,et al.  Cornell scale for depression in dementia , 1988, Biological Psychiatry.

[18]  A. Georgotas,et al.  The additional benefit of extending an antidepressant trial past seven weeks in the depressed elderly , 1989 .

[19]  E. Halgren,et al.  Intracerebral potentials to rare target and distractor auditory and visual stimuli. III. Frontal cortex. , 1995, Electroencephalography and clinical neurophysiology.

[20]  D. Delis,et al.  The subcortical dysfunction hypothesis of memory deficits in depression: neuropsychological validation in a subgroup of patients. , 1992, Journal of clinical and experimental neuropsychology.

[21]  I. Hickie,et al.  Subcortical hyperintensities on magnetic resonance imaging: Clinical correlates and prognostic significance in patients with severe depression , 1995, Biological Psychiatry.

[22]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[23]  E. Stern,et al.  Target Detection and the Prefrontal Cortex. A PET Scan Study of the P300 Event‐Related Potential , 1995, Annals of the New York Academy of Sciences.

[24]  M. Carney,et al.  Depression and Newcastle scales. Their relationship to Hamilton's scale. , 1972, The British journal of psychiatry : the journal of mental science.

[25]  Karl J. Friston,et al.  The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression , 1992, Psychological Medicine.

[26]  R G Robinson,et al.  Differential mood changes following basal ganglia vs thalamic lesions. , 1988, Archives of neurology.

[27]  J. Mazziotta,et al.  Reduction of prefrontal cortex glucose metabolism common to three types of depression. , 1989, Archives of general psychiatry.

[28]  E. Caine,et al.  Cognitive impairment and major depression: Beyond the pseudodementia syndrome. , 1996 .

[29]  Richard S. J. Frackowiak,et al.  Anatomy of motor learning. I. Frontal cortex and attention to action. , 1997, Journal of neurophysiology.

[30]  C. Tenke,et al.  Brain event-related potentials to complex tones in depressed patients: relations to perceptual asymmetry and clinical features. , 1995, Psychophysiology.

[31]  E. Robins,et al.  Research diagnostic criteria. , 1975, Psychopharmacology bulletin.

[32]  P. Fox,et al.  Cingulate function in depression: a potential predictor of treatment response , 1997, Neuroreport.

[33]  A. Starr,et al.  Cognitive evoked potentials (P300) in early Huntington's disease. , 1985, Archives of neurology.

[34]  N C Andreasen,et al.  The family history method using diagnostic criteria. Reliability and validity. , 1977, Archives of general psychiatry.

[35]  D. Stuss,et al.  Neuropsychological studies of the frontal lobes. , 1984, Psychological bulletin.

[36]  H. Sackeim,et al.  Psychomotor symptoms of depression. , 1997, The American journal of psychiatry.

[37]  Sati Mazumdar,et al.  Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale , 1992, Psychiatry Research.

[38]  M. Yamada,et al.  [Dementia rating scale]. , 1997, Nihon rinsho. Japanese journal of clinical medicine.

[39]  E. Robins,et al.  Research diagnostic criteria: rationale and reliability. , 1978, Archives of general psychiatry.