Ventromedial syndrome with normal cognitive functioning in vascular depression.

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Back to table of contents Previous article Next article Communications and UpdatesFull AccessVentromedial Syndrome With Normal Cognitive Functioning in Vascular DepressionKevin J. Manning, Ph.D. Faith M. Gunning, Ph.D. Amanda R. McGovern, Ph.D. Nabil Kotbi, M.D. George S. Alexopoulos, M.D.Kevin J. ManningSearch for more papers by this author, Ph.D. Faith M. GunningSearch for more papers by this author, Ph.D. Amanda R. McGovernSearch for more papers by this author, Ph.D. Nabil KotbiSearch for more papers by this author, M.D. George S. AlexopoulosSearch for more papers by this author, M.D.Published Online:1 Dec 2014https://doi.org/10.1176/appi.ajp.2014.14050595AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Previously, we described a late-life depression-executive dysfunction syndrome associated with disability (1). Microstructural white matter abnormalities, common in this syndrome, are principally caused by cerebrovascular changes and contribute to executive dysfunction and resistance to antidepressants (2).We recently treated a 71-year-old woman in the third episode of early-onset (mid-thirties) major depression, who was hospitalized after an overdose. She had a dysexecutive behavioral syndrome, prominent hyperintensities on MRI (Figure 1), but no impairment on executive function tests. She presented with mood lability and poor monitoring of her own behavior (i.e., repetition, distractibility, and impulsivity). She performed in the average to superior range on tasks of processing speed (Trail-Making Test, Part A, 73rd percentile), cognitive inhibition (Stroop test, 66th percentile), set-shifting (Trail-Making Test, Part B, 96th percentile; Wisconsin Card Sorting Test, 61st percentile), and planning (Tower of London Test, 75th percentile). She was partially aware of her pathology, noting, “I want to change the habit of speaking out without thinking and acting impulsively.” Her husband’s report on the Frontal Systems Behavior Scale (3) showed major abnormalities in “disinhibition,” with much milder abnormalities in the “dysexecutive” and “apathy” domains.FIGURE 1. MRI Findings in a 71-Year-Old Woman in Her Third Episode of Early-Onset DepressionaaScan 1 and scan 2 are positioned left to right; however, normal radiological conventions apply (right is left, left is right).This patient’s behavior was consistent with ventromedial cortex dysfunction. Lesions in this area may disconnect frontal monitoring systems from limbic output, resulting in prominent mood lability, behavioral disinhibition, and inappropriate behavior and judgment (4). Patients with ventromedial cortex dysfunction may have intact executive functioning primarily served by dorsolateral prefrontal cortex and dorsal anterior cingulate circuitry (4).Behavioral abnormalities related to the ventromedial cortex have seldom been investigated in late-life depression. We recently conducted a cluster analysis of 52 adults with late-life depression and identified three patient subgroups. Cluster 1 (N=20) performed poorly on a task requiring ventromedial cortex integrity (Iowa gambling task) but performed well on cognitive control tasks (Stroop Color and Word Test, Tower of London Test) and had no apathy. Cluster 2 (N=19) performed well on the Iowa gambling task, had impaired performance on the Stroop Color and Word and Tower of London tests, and had mild apathy. Cluster 3 (N=13) performed well on the Iowa gambling task, the Stroop Color and Word Test, and the Tower of London Test but had significant apathy. Impairment in risk-sensitive decision making has been documented in older suicide attempters (5), suggesting that select patients may present with ventromedial cortex impairment. We suggest that disinhibited behavior, dissociable from cognitive control dysfunction, characterizes a subgroup of late-life depression whose neurobiology and treatment response require investigation.From the Department of Psychiatry, University of Connecticut Health Center, Farmington, Conn.; and Weill Cornell Medical College, Institute of Geriatric Psychiatry, New York Presbyterian Hospital, White Plains, New York.Dr. Gunning receives grant support from NIMH to support research on cerebral networks important in the presentation and antidepressant response of late-life depression. Dr. Alexopoulos has received grant support from Forest, has served on the advisory panels of Forest, Hoffman LaRoche, Janssen, Lilly, Lundbeck, Otsuka, and Pfizer, and has served on the speakers' bureaus of AstraZeneca, Avanir, Forest, Merck, Novartis, Sunovion, and Takeda/Lundbeck. All other authors report no financial relationships with commercial interests.References1 Alexopoulos GS: The depression-executive dysfunction syndrome of late life: a specific target for D3 agonists? Am J Geriatr Psychiatry 2001; 9:22–29Medline, Google Scholar2 Taylor WD, Aizenstein HJ, Alexopoulos GS: The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 2013; 18:963–974Crossref, Medline, Google Scholar3 Grace J, Malloy P: Frontal Systems Behavior Scale (FrSBe): Professional Manual. Lutz, Fla, Psychological Assessment Resources, 2001Google Scholar4 Bonelli RM, Cummings JL: Frontal-subcortical circuitry and behavior. Dialogues Clin Neurosci 2007; 9:141–151Medline, Google Scholar5 Clark L, Dombrovski AY, Siegle GJ et al.: Impairment in risk-sensitive decision-making in older suicide attempters with depression. Psychol Aging 2011; 26:321–330Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByInternational Psychogeriatrics, Vol. 27, No. 12Annals of the New York Academy of Sciences, Vol. 1345, No. 1 Volume 171Issue 12 December 01, 2014Pages 1337-1338 Metrics PDF download History Accepted 1 September 2014 Published online 1 December 2014 Published in print 1 December 2014