Skip to main content Accessibility help

Affective Disorders and Cerebral Vascular Disease

  • Sergio E. Starkstein (a1) and Robert G. Robinson (a2)


Empirical studies have recently demonstrated that major and minor depressive disorders occur in 30–50% of stroke patients, and last more than one year without treatment, although they do respond to tricyclic antidepressants. These mood disorders are not strongly associated with severity of impairment, demographic characteristics, social supports or prior personal history, but major depression is often strongly associated with left frontal or left basal ganglia lesions and pre-existing subcortical atrophy. While the aetiology of these mood disorders remains unknown, serotonergic or noradrenergic dysfunction may play a role. Mania is a rare complication of stroke: the clinical presentation and response to treatment are usually the same as mania without brain injury. Post-stroke mania is strongly associated with both a right hemisphere lesion in a limbic-connected area and a second predisposing factor, such as genetic loading for affective disorder, pre-existing subcortical atrophy or seizure disorder. This disorder may be mediated through frontal lobe dysfunction. The lesion method represents a potentially fruitful technique for investigating the mechanisms of affective disorder.


Corresponding author

Adolf Meyer Building 4–119, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA


Hide All
American Psychiatric Association (1980) Diagnostic Criteria from Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. Washington DC: APA.
Babinksi, J. (1922) Réflexes de defense. Brain, 45, 149184.
Baron, J. C. (1985) Positron tomography in cerebral ischemia. Neuroradiology, 27, 509516.
Belyi, B. I. (1987) Mental impairment in unilateral frontal tumors: role of the laterality of the lesion. International Journal of Neuroscience, 32, 799810.
Benson, D. F. (1973) Psychiatric aspects of aphasia. British Journal of Psychiatry, 123, 555566.
Bleuler, E. P. (1951) Textbook of Psychiatry. New York: Dover Publications.
Council on Scientific Affairs (1988) Magnetic resonance imaging of the central nervous system. Journal of the American Medical Association, 259, 12111222.
Cummings, J. L. & Mendez, M. F. (1984) Secondary mania with focal cerebrovascular lesions. American Journal of Psychiatry, 141, 10841087.
de Bonis, M., Dellatolas, G. & Rondot, P. (1985) Mood disorders in left and right brain damaged patients: comparison between ratings and self-ratings on the same adjective mood scale: some methodological problems. Psychopathology, 18, 286292.
Ebrahim, S., Barer, K D. & Nouri, F. (1987) Affective illness after stroke. British Journal of Psychiatry, 151, 5256.
Feeney, D. M. & Baron, J. C. (1986) Diaschisis. Stroke, 17, 817830.
Feibel, J. H. & Springer, C. J. (1982) Depression and failure to resume social activities after stroke. Archives of Physical and Medical Rehabilitation, 63, 276.
Finklestein, S., Benowitz, L. I., Baldessarini, R. J., et al (1981) Mood, vegetative disturbance, and dexamethasone suppression test after stroke. Annals of Neurology, 12, 463468.
Fisher, S. (1961) Psychiatric considerations of cerebral vascular disease. American Journal of Cardiology, 7, 379.
Fogel, B. S. & Sparadeo, F. R. (1985) Focal cognitive deficits accentuated by depression. Journal of Nervous and Mental Disease, 173, 120124.
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975) Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.
Folstein, M. F., Maiberger, R. & McHugh, P. R. (1977) Mood disorder as a specific complication of stroke. Journal of Neurology, Neurosurgery and Psychiatry, 40, 10181020.
Forrest, D. V. (1982) Bipolar illness after right hemispherectomy. Archives of General Psychiatry, 39, 817819.
Gainotti, G. (1972) Emotional behavior and hemispheric side of the lesion. Cortex, 8, 4155.
Gasparrini, W. G., Satz, P., Heilman, K. M., et al (1978) Hemispheric asymmetries of affective processing as determined by the Minnesota Multiphasic Personality Inventory. Journal of Neurology, Neurosurgery and Psychiatry, 41, 470473.
Goldberg, D. P. & Hiller, V. F. (1979) A scaled version of the General Health Questionnaire. Psychological Medicine, 9, 139145.
Goldstein, K. (1948) Language and Language Disturbances. New York: Grunne and Stratton.
Jorm, A. F. (1986) Cognitive deficit in the depressed elderly: a review of some basic unresolved issues. Australian and New Zealand Journal of Psychiatry, 20, 1122.
Kellar, K. J., Cascio, C. S., Butler, J. A., et al (1981) Differential effects of electroconvulsive shock and antidepressant drugs on serotonin-2 receptors in rat brain. European Journal of Pharmacology, 69, 515518.
Kellner, A. H., Rubinow, D. R. & Post, R. M. (1986) Cerebral ventricular size and cognitive impairment in depression. Journal of Affective Disorders, 10, 215219.
Kertesz, A., Black, S. E., Nicholson, L., et al (1987) The sensitivity and specificity of MRI in stroke. Neurology, 37, 15801585.
Kraepelin, E. (1921) Manic Depressive Insanity and Paranoia. Edinburgh: E. and S. Livingstone.
Krauthammer, C. & Klerman, G. L. (1978) Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Archives of General Psychiatry, 35, 13331339.
Labi, M. L. C., Phillips, T. F. & Gresham, G. E. (1980) Psychosocial disability in physically restored long-term stroke survivors. Archives of Physical Medicine and Rehabilitation, 61, 561565.
Lipsey, J. R., Robinson, R. G., Pearlson, G. D., et al (1983). Mood change following bilateral hemisphere brain injury. British Journal of Psychiatry, 143, 266273.
Lipsey, J. R., Robinson, R. G., Pearlson, G. D., et al (1984) Nortriptyline treatment for post-stroke depression: a double-blind study. Lancet, i, 297300.
Lipsey, J. R., Robinson, R. G., Pearlson, G. D., et al (1985) Dexamethasone suppression test and mood following strokes. American Journal of Psychiatry, 142, 318323.
Lipsey, J. R., Spencer, W. C., Rabins, P. V., et al (1986) Phenomenological comparson of post-stroke depression and functional depression. American Journal of Psychiatry, 143, 527529.
Mayberg, H. S., Robinson, R. G., Wong, D. F., et al (1988) PET imaging of cortical S2-serotonin receptors following stroke: lateralized changes and relationship to depression. American Journal of Psychiatry, 145, 937943.
Meyer, A. (1904) The anatomical facts and clinical varieties of traumatic insanity. American Journal of Insanity, 60, 373.
Morris, P. L. P. & Raphael, B. (1987) Depressive disorder associated with physical illness: the impact of stroke. General Hospital Psychiatry, 9, 324330.
Morrison, J. H., Molliver, M. E. & Grzanna, R. (1979) Noradrenergic innervation of the cerebral cortex: widespread effects of local cortical lesions. Science, 205, 313316.
Murray, G. B., Shea, V. & Conn, D. K. (1987) Electroconvulsive therapy for post-stroke depression. Journal of Clinical Psychiatry, 47, 258260.
Oradei, D. M. & Waite, N. S. (1974) Group psychotherapy with stroke patients during the immediate recovery phase. American Journal of Orthopsychiatry, 44, 386395.
Parikh, R. M., Lipsey, J. R., Robinson, R. G., et al (1987) Two-year longitudinal study of post-stroke mood disorders: dynamic changes in correlates of depression at one and two years. Stroke, 18, 579584.
Pearlson, G. D. & Robinson, R. G. (1981) Suction lesions of the frontal cerebral cortex in the rat induce asymmetrical behavioral and catecholaminergic responses. Brain Research, 218, 233242.
Pickel, V. M., Segal, M. & Bloom, F. E. (1974). A radio-autographic study of the efferent pathways of the nucleus locus coeruleus. Journal of Comparative Neurology, 155, 1542.
Pope, H. G., McElroy, S. L., Satlin, A., et al (1988) Head injury, bipolar disorder, and response to valproate. Comprehensive Psychiatry, 29, 3438.
Reding, M. J., Orto, L. A., Willenski, P., et al (1985) The dexamethasone suppression test: an indicator of depression in stroke but not a predictor of rehabilitation outcome. Archives of Neurology, 42, 209212.
Reding, M. J., Orto, L. A., Winter, S. W., et al (1986) Antidepressant therapy after stroke: a double-blind trial. Archives of Neurology, 43, 763765.
Reis, D. J. & Ross, R. A. (1973) Dynamic changes in brain dopamine B-hydroxilase activity during anterograde and retrograde reactions to injury of central noradrenergic axons. Brain Research, 57, 307326.
Robinson, R. G. (1979) Differential behavioral and biochemical effects of right and left hemispheric cerebral infarction in the rat. Science, 205, 707710.
Robinson, R. G., Shoemaker, W. J., Schlumpf, M., et al (1975) Effect of experimental cerebral infarction in rat brain: effect on catecholamines and behavior. Nature, 255, 332334.
Robinson, R. G. & Benson, D. F. (1981) Depression in aphasic patients: frequency, severity and clinical pathological correlations. Brain and Language, 14, 282291.
Robinson, R. G. & Price, T. R. (1982) Post-stroke depressive disorders: a follow-up study of 103 patients. Stroke, 13, 635641.
Robinson, R. G., Starr, L. B., Kubos, K. L., et al (1983a) A two-year longitudinal study of post-stroke mood disorder: findings during the initial evaluation. Stroke, 14, 736741.
Robinson, R. G., Kubos, K. L., Starr, L. B., et al (1983b) Mood changes in stroke patients: relationship to lesion location. Comprehensive Psychiatry, 24, 555566.
Robinson, R. G., Starr, L. B., Lipsey, J. R., et al (1984a) A two-year longitudinal study of mood disorders following stroke: prevalence and duration at six months follow-up. British Journal of Psychiatry, 144, 256262.
Robinson, R. G., Kubos, K. G., Starr, L. B., et al (1984b) Mood disorders in stroke patients: importance of location of lesion. Brain, 107, 8193.
Robinson, R. G., Starr, L. B., Lipsey, J. R., et al (1984c) A two-year longitudinal study of post-stroke mood disorders: dynamic changes over the first six months of follow-up. Stroke, 15, 510517.
Robinson, R. G. & Lipsey, J. R. (1985) Cerebral localization of emotion based on clinical–neuropathological correlations: methodological issues. Psychiatric Developments, 4, 335347.
Robinson, R. G. & Lipsey, J. R., Bolla-Wilson, K., et al (1985a) Mood disorders in left-handed stroke patients. American Journal of Psychiatry, 142, 14241429.
Robinson, R. G., Starr, L. B., Lipsey, J. R., et al (1985b) A two-year longitudinal study of post-stroke mood disorders: in-hospital prognostic factors associated with six-month outcome. Journal of Nervous and Mental Disease, 173, 221226.
Robinson, R. G., Bolla-Wilson, K., Kaplan, E., et al (1986) Depression influences intellectual impairment in stroke patients. British Journal of Psychiatry, 148, 541547.
Robinson, R. G., Bolduc, P. L. & Price, T. R. (1987) Two-year longitudinal study of post-stroke mood disorders: diagnosis and outcome at one and two years. Stroke, 18, 837843.
Robinson, R. G., Boston, J. D., Starkstein, S. E., et al (1988a) Comparison of mania with depression following brain injury: causal factors. American Journal of Psychiatry, 145, 172178.
Robinson, R. G., Starkstein, S. E. & Price, T. R. (1988b). Post stroke depression and lesion location. Stroke, 19, 125.
Ross, E. D. & Rush, A. J. (1981) Diagnosis and neuroanatomical correlates of depression in brain damaged patients. Archives of General Psychiatry, 38, 13441354.
Ross, E. D., Gordon, W. A., Hibbard, M., et al (1986) The dexamethasone suppression test, post-stroke depression, and the validity of DSM–III-based diagnostic criteria. American Journal of Psychiatry, 143, 12001201.
Rosse, R. B. & Ciolino, C. P. (1986) Effects of cortical lesion location on psychiatric consultation referral for depressed stroke inpatients. International Journal of Psychiatry in Medicine, 15, 311320.
Shukla, S., Cook, B. L., Mukherjee, S., et al (1987) Mania following head trauma. American Journal of Psychiatry, 144, 9396.
Sinyor, D., Jacques, P., Kaloupek, D. G., et al (1986a) Post-stroke depression and lesion location: an attempted replication. Brain, 109, 537546.
Sinyor, D., Amato, P., Kaloupek, D., et al (1986b) Post-stroke depression: relationship to functional impairment, coping strategies, and rehabilitation outcome. Stroke, 17, 11021107.
Spitzer, R. J., Endicott, J. & Robins, E. (1975) Research Diagnostic Criteria (RDC) for a Group of Functional Disorders. New York: New York Psychiatric Institute.
Starkstein, S. E., Robinson, R. G. & Price, T. R. (1987a) Comparison of cortical and subcortical lesions in the production of post-stroke mood disorders. Brain, 110, 10451059.
Starkstein, S. E., Pearlson, G. D., Boston, J. D., et al (1967b). Mania after brain injury: a controlled study of causative factors. Archives of Neurology, 44, 10691073.
Starkstein, S. E., Robinson, R. G., Berthier, M. L., et al (1988a) Depressive disorders following posterior circulation compared with middle cerebral artery infarcts. Brain, 111, 375387.
Starkstein, S. E., & Robinson, R. G.,(1988b) Aphasia and depression. Aphasiology, 2, 120.
Starkstein, S. E., Robinson, R. G., & Price, T. R. (1988c) Comparison of patients with and without post-stroke major depression matched for size and location of lesion. Archives of General Psychiatry, 45, 247252.
Starkstein, S. E., Boston, J. D. & Robinson, R. G. (1988d) Mechanisms of mania following brain injury: twelve case reports and review of the literature. Journal of Nervous and Mental Disease, 176, 87100.
Starkstein, S. E., Robinson, R. G. & Honig, M. A. (1989) Mood changes after right hemisphere lesions. British Journal of Psychiatry (in press).
Starr, L. B., Robinson, R. G. & Price, T. R. (1983) Reliability, validity, and clinical utility of the Social Functioning Exam in the assessment of stroke patients. Experimental Aging Research, 9, 101110.
Swerdlow, N. R. & Koob, G. F. (1967) Dopamine, schizophrenia, mania, and depression: toward a unified hypothesis of cortico-striato-pallido-thalamic function. Behavioral and Brain Sciences, 10, 197245.
Wade, D. T., Lech-Smith, J. E. & Hewer, R. A. (1987) Depressed mood after stroke: a community study of its frequency. British Journal of Psychiatry, 151, 200205.
Watziawick, P. & Coyne, J. C. (1980) Depression following stroke: brief, problem-focussed family treatment. Family Treatment, 19, 1318.
Wing, J. K., Cooper, E. & Sartorius, N. (1974) Measurement and Classification of Psychiatric Symptoms. Cambridge: Cambridge University Press.
Wong, D. F., Wagner, H. N., Dannals, R. F., et al (1984) Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science, 226, 13931396.

Related content

Powered by UNSILO

Affective Disorders and Cerebral Vascular Disease

  • Sergio E. Starkstein (a1) and Robert G. Robinson (a2)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Affective Disorders and Cerebral Vascular Disease

  • Sergio E. Starkstein (a1) and Robert G. Robinson (a2)
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *