A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.

https://neuro.psychiatryonline.org/doi/pdfplus/10.1176/jnp.9.3.471

Limbic-cortical dysregulation: a proposed model of depression.

It was recently proposed that the affective components of language, encompassing prosody and emotional gesturing, are a dominant function of the right hemisphere, and that their functional-anatomic organization in the right hemisphere mirrors that of propositional language in the left hemisphere. Ten right-handed patients with focal lesions of the right hemisphere and disorders of affective language are described. Observations were made about each patient's spontaneous prosody, prosodic repetition, prosodic comprehension, and comprehension of emotional gesturing. Using this particular examination strategy, which is derived from the usual bedside approach to aphasic disorders, the organization of affective language in the right hemisphere does mirror the organization of propositional language in the left hemisphere. Furthermore, the disorders of affective language seem to be classifiable in the same manner as the aphasias. Thus, the term "aprosodia," preceded by specific modifiers such as motor, global, transcortical sensory, etc, seems appropriate when classifying the various disorders of affective language that occur following-right-hemisphere damage. The relationships between affect, mood, pathologic laughing and crying, and depression are also discussed.

https://jamanetwork.com/journals/NEUR/articlepdf/580070/archneur_38_9_006.pdf

The Aprosodias: Functional-Anatomic Organization of the Affective Components of Language in the Right Hemisphere

BACKGROUND AND PURPOSE: This prospective study was designed to examine the contributions of neurobiological, functional, and psychosocial factors to major depression after stroke. In addition, the ...

Major depression in stroke patients : A 3-year longitudinal study

Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.

https://jamanetwork.com/journals/PSYCH/articlepdf/493564/archpsyc_42_5_002.pdf

Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18.

Objective: The goals ofthis longitudinal investigation were 1) to study the rate of development of irreversible dementia in elderly depressed patients with a dementia syndrome that subsided after improvement ofdepression and 2) to compare it with that ofdepressed, neverdemented patients. Method: The subjects were 57 elderly patients consecutively hospitalized f or major depression. At entry into the study, 23 subjects also met criteria for “reversible dementia, “ while 34 were without dementia. After a systematic clinical evaluation, the subjects were followed up at approximately yearly intervals for an average of 33.8 months. Results: Irreversible dementia developed significantly more frequently in the depressed group with reversible dementia (43 %) than in the group with depression alone (1 2%). Survival analysis showed that the group with reversible dementia had a 4.69-times higher chance of having developed dementia at follow-up than the patients with depression alone. No clinical characteristics at entry into the study were found to discriminate the subjects who developed irreversible dementia during the follow-up period from those who remained nondemented. � clusions: These findings suggest that geriatric depression with reversible dementia is a clinical entity that includes a group ofpatients with early-stage dementing disorders. Therefore, identification ofa reversible dementia syndrome is an indication for a thorough diagnostic workup and frequent follow-ups in order to identify treatable neurological disorders. (Am-”J Psychiatry 1993; 150:1693-1699)

The Course of Geriatric Depression With "Reversible Dementia": A Controlled Study

• Recognizing depression in brain-damaged patients poses considerable problems. The standard dignostic criteria often are not applicable since the neurological lesion may distort or even obliterate salient features of depression. Patients actually may deny being depressed or dysphoric, not have a depressive affect, or be totally unaware of abnormal vegetative behaviors. Furthermore, brain lesions themselves may produce striking behavioral alterations that can be mistakenly attributed to depression, or striking behavioral changes due to depression may be mistakenly attributed to the brain lesion. Based on five case studies, several clinical guidelines for recognizing and diagnosing depression in brain-damaged patients are offered. These cases also provide a data base to generate initial hypotheses about the neuroanatomical basis of the depressive syndrome. By observing how focal brain lesions modify the signs and symptoms of depression, inferences are made about brain areas crucial for modulating the various features of the depressive syndrome.

Elliott D. Ross

Papers

Diagnosis and neuroanatomical correlates of depression in brain-damaged patients. Implications for a neurology of depression.