Background and Purpose We previously found that silent cerebral infarction (SCI) was present in most of the patients older than 50 years with major depression who were examined. The present study was designed to clarify the relationship between psychosocial stressors and SCI in patients with major depression.
Methods Forty-two patients with unipolar depression underwent MRI and were classified as SCI-negative (n=19) or SCI-positive (n=23). The SCI-positive group was subclassified into those with moderate SCI (n=16) and those with severe SCI (n=7). The relationship between the patients’ DSM-III-R axis IV scores and SCI was evaluated.
Results The axis IV score was significantly lower in the SCI-positive group than in the SCI-negative group (P<.05). Within the SCI-positive group, the mean axis IV score was significantly lower in those with severe SCI than in those with moderate SCI (P<.05).
Conclusions Our findings suggest that depression in patients with SCI involves more neurological factors than psychosocial stressors.
When a cerebral infarction detected by MRI or other imaging modalities is not associated with a stroke or focal neurological symptoms, it is referred to as a silent cerebral infarction (SCI). Such infarcts fit into classification III for cerebrovascular disorders (CVD III), published by the American National Institute of Neurological Disorders and Stroke Ad Hoc Committee.1 We previously studied the relationship between depression in old age and SCI as detected by MRI. We found that an SCI was present in most of the patients older than 50 years with major depression examined2 ; in addition, the patients with major depression and SCI demonstrated risk factors for cerebral infarction (eg, hypertension) more frequently than did those without SCI.3 Mania of late onset (at age >50 years) is associated with larger areas of brain damage (both perforating and cortical areas) than is major depression of late onset (at age >50 years).4 Our data revealed that the depressed patients with severe SCI (both perforating and cortical areas) required longer hospital treatment and had more antidepressant-induced adverse reactions of the central nervous system than did those with moderate SCI (either perforating area or cortical area).5
Psychosocial stressors are often related to the onset of depression. In old age, stressors such as retirement and divorce played a role at the onset of depression in a life-event study of depression conducted in a large population.6 In the DSM-III-R,7 axis IV is the assessment of the severity of psychosocial stressors. Skodol and Shrout8 and Rey et al9 studied the reliability of axis IV compared with more extensive systems for measuring life-event stress such as the Psychiatric Epidemiology Research Interview and Psychosocial Adversity Index, and the results indicated that the axis IV rating is consistent with meaningful diagnostic and demographic group differences.
In the present study we examined the relationship between neurological factors (such as SCI) and the severity of psychosocial stressors in patients older than 50 years with major depression. We hypothesized that patients with SCI would have stronger evidence of neurological factors than would those without SCI and would have less evidence of severe psychosocial stressors at the onset of depression. Axis IV of the DSM-III-R was used as an indicator of the severity of psychosocial stressors.
Subjects and Methods
Patients older than 50 years of age who were admitted to the Department of Psychiatry and Neurosciences at Hiroshima University School of Medicine between January 1993 and December 1995 for unipolar depression were evaluated retrospectively by a review of their clinical charts. Their data had been collected for routine clinical care. All of these patients underwent routine MRI within 3 months after admission and met the DSM-III-R criteria for major depression as determined by a clinical interview. All patients received a neurological examination at the time of admission by their physician (psychiatrist), and patients with evidence of stroke or focal neurological symptoms were excluded from the study. SCI was diagnosed according to the CVD III criteria. Patients with alcoholism, cerebral degenerative disease or dementia, brain injury, or systemic disease or medications (eg, steroids) that could induce depression were also excluded. All patients underwent a detailed interview by their physician at the time of admission, and the DSM-III-R diagnosis was discussed at the patient conference; all patients received an adequate and appropriate DSM-III-R diagnosis. All patients underwent questioning regarding the age at onset of depression and antihypertensive medications. All patients were treated in accordance with institutional guidelines and were approved by an institutional review committee. The relationship between the patients’ DSM-III-R axis scores and SCI was evaluated in the present investigation.
For statistical analysis, the relationship between age and the DSM-III-R axis IV score was determined by simple regression analysis; mean±SD values were calculated for parametric data, and Student’s t test was used to compare groups. The χ2 test and Mann-Whitney test were used for the comparison of nonparametric numerical data in each group. Values of P<.05 were considered significant.
Axis IV of the DSM-III-R
Axis IV of the DSM-III-R provides a scale called the Severity of Psychosocial Stressors Scale for coding the overall severity of psychosocial stressors that have occurred in the year preceding the current evaluation and that may have contributed to any of the following: (1) development of a new mental disorder, (2) recurrence of a prior mental disorder, and (3) exacerbation of an already existing mental disorder.
Code 1 of this scale indicates no psychosocial stressors (no acute events that may be relevant to the disorder, or no enduring circumstances that may be relevant to the disorder). Code 2 indicates mild psychosocial stressors (acute events such as breaking up with boyfriend or girlfriend, started or graduated from school, child left home, or family arguments; enduring circumstances such as job dissatisfaction, residence in high-crime neighborhood). Code 3 indicates moderate psychosocial stressors (acute events such as marriage, marital separation, loss of job, retirement, or miscarriage; enduring circumstances such as marital discord, serious financial problems, trouble with boss, or being a single parent). Code 4 indicates severe psychosocial stressors (acute events such as divorce, birth of first child; enduring circumstances such as unemployment, poverty). Code 5 indicates extreme psychosocial stressors (acute events such as death of spouse, serious physical illness diagnosed, or being a victim of rape; enduring circumstances such as serious chronic illness in self or child and ongoing physical or sexual abuse). Code 6 indicates catastrophic psychosocial stressors (acute events such as death of child, suicide of spouse, devastating natural disaster; enduring circumstances such as captivity as hostage, concentration camp experience).
MRI was performed with a 1.5-T apparatus (General Electric Co) at the Hiroshima University School of Medicine. T2-weighted images (TR, 2000 ms; TE, 100 ms) were obtained in the transverse plane parallel to the orbitomeatal line, and T1-weighted images (inversion-recovery; TR, 2000 ms; TE, 100 ms) were obtained as coronal slices at 10-mm intervals. Twelve slices were used for each type of image. Infarcts were defined as high-intensity lesions larger than 5 mm in diameter on T2-weighted images, and those coincided with low-intensity lesions on T1-weighted images according to the proposition of Braffman et al.10 Lesions that measured from 5 to 20 mm on all slices were defined as small infarcts, and larger lesions were classified as large infarcts.
Regarding the number of small infarcts that can be interpreted as representative of an SCI, Shimada et al11 reported that the mean number of small infarcts in asymptomatic, hypertensive elderly subjects was 2.8±4.6, whereas that in normotensive elderly subjects was 1.1±1.5. Matsubayashi et al12 reported that four or more small infarcts are associated with the development of cognitive impairment in elderly patients. SCI was therefore defined as one or more large infarcts or as the presence of four or more small infarcts in the same cerebral hemisphere. In the present study, patients with fewer than four small infarcts and no large infarcts were classified as not having SCI. Periventricular hyperintensity was not assessed.
Cerebral infarctions were classified as follows: SCI in the perforating branch referred to lesions in the basal ganglia, the internal capsules, and the thalami. SCI in the cortical branch referred to lesions in the cerebral cortex and subcortical white matter. Details regarding the location and hemisphere of SCI were not assessed because almost all patients had multiple lesions.
Patients were classified by MRI findings into an SCI-negative group and an SCI-positive group, and the latter group was subclassified according to infarction area as those with moderate SCI (either perforating branch or cortical branch) or severe SCI (both perforating branch and cortical branch). MRI scans were combined in a randomized order and evaluated by a research psychiatrist (T.F. or I.Y.) before the data were collected.
A total of 35 patients were each admitted once between January 1993 and December 1995, and 7 other patients were each admitted twice during that period. Only first admissions for the latter group were studied. Thus, a total of 42 admissions were investigated.
A regression analysis revealed that the axis IV scores were not correlated with age (r=.207, P=.19). The relationship between SCI and axis IV score is shown in the Table⇓. Nineteen patients were negative for SCI, and 23 were SCI-positive. In the SCI-positive group, 16 patients had moderate SCI and 7 had severe SCI. Three patients in the SCI-negative group had early-onset depression (aged <50 years), and 3 patients in the SCI-positive group (2 patients in the moderate SCI group and 1 patient in the severe SCI group) had early-onset depression. No patients in the SCI-negative group were taking antihypertensive drugs, and 2 patients in the SCI-positive group (1 moderate SCI patient and 1 severe SCI patient) were taking a calcium antagonist.
The mean age was significantly lower in the SCI-negative group than in the SCI-positive group (P<.05). The mean axis IV score was significantly lower in the SCI-positive group (1.96±1.12) than in the SCI-negative group (2.63±1.13) (P<.05). Within the SCI-positive group, the mean axis IV score was significantly lower in the patients with severe SCI (1.29±0.70) than in those with moderate SCI (2.25±1.15) (P<.05). There was no significant difference between the moderate SCI and SCI-negative groups in the mean axis IV score.
A complex of neurological factors, genetic factors, and psychosocial stressors is related to the onset of depression. Both neurological factors and genetic factors are specific to individual patients. Psychosocial stressors are environmental factors for each patient. Endogenous depression is considered to involve a basic biological susceptibility and to be largely uninfluenced by life stresses.13 14
In contrast to genetic factors, structural neurological changes appear to be of primary importance in the etiology of late-onset depression. As shown in our previous report, SCI has frequently been identified by MRI in patients older than 50 years with major depression.2 3 4 5 Therefore, we studied the relationships between neurological factors and the severity of psychosomatic stressors.
We hypothesized that patients with SCI would show stronger evidence of neurological factors than would those without SCI and less evidence of severe psychosocial stressors at the onset of depression, and this hypothesis was supported by the present findings. Although there was no significant difference between the moderate SCI and SCI-negative groups in the mean axis IV score, the axis IV score in the SCI-positive group was significantly lower than that in the SCI-negative group. Within the SCI-positive group, the axis IV score was significantly lower in the patients with severe SCI than in those with moderate SCI. Although the mean age was significantly lower in the SCI-negative group than in the SCI-positive group, there have been no previous reports that the severity of psychosocial stressors in depressed patients decreases with aging. Thus, the conditions that caused depression in our present patients were related more closely to severe neurological factors than to psychosocial stressors.
In individual patients, neurological factors might cause depression even without psychosocial stressors, and thus SCI-positive and SCI-negative depression may have different etiologies.
Selected Abbreviations and Acronyms
|CVD III||=||classification III for cerebrovascular disorders|
|DSM-III-R||=||Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised|
|SCI||=||silent cerebral infarction|
- Received November 7, 1996.
- Revision received March 24, 1997.
- Accepted March 24, 1997.
- Copyright © 1997 by American Heart Association
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