5
41
Method of diagnosis
For a number of years the generally accepted method for research diagnoses of psychiatric disorders has been to conduct a structured or semi-structured mental status interview to elicit the presence and duration of symptoms of the disorder and apply these to Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria for that disorder. The current DSM-IV TR (American Psychiatric Association 2000) has identified a category of disorders which are judged by the clinician to be the consequence of a general medical con-dition. The DSM-IV diagnostic criteria for mood disorders due to stroke or other medical disorders are shown in Table 5.1. At the present time, although there is some debate in the literature as to the most appropriate way to diagnose depression in patients with brain injury, this is the accepted criteria and method for diagnosis in psychiatry.
There are a number of structured and semi-structured interviews for diagnosis in psychiatry and investigators of poststroke depression have utilized a wide vari-ety of these instruments. Eastwood et al. and we have recently used the Schedule for Affective Disorders and Schizophrenia (SADS) (Eastwood et al. 1989; Robinson 2000). Morris et al. (1990) used the Composite Index of Diagnostic Interviews (CIDI). Throughout most of our studies, we and other investigators have used the Present State Examination (PSE) (Robinson and Price 1982; House et al. 1990;
Pohjasvaara et al. 1998), which is a semi-structured interview that we have modi-fied to elicit all of the specific symptoms required for a DSM-IV diagnosis of mood or anxiety disorder. The full spectrum of instruments is shown in Table 6.1 on the prevalence of poststroke depression. Although some authors have expressed a pref-erence for one interview over another, a comparison of diagnostic instruments has not been conducted in poststroke mood disorders.
Although the use of a structured or semi-structured psychiatric interview has clearly been the accepted method for systematic elicitation of symptomology, a
42 Poststroke depression
surprising number of studies have utilized a cutoff score on a depression rating scale for an approximation to the diagnosis of depression (Sinyor et al. 1986; Collin et al. 1987; Wade et al. 1987; Andersen et al. 1994; Kotila et al. 1998; Desmond et al.
2003). The consistency of findings in mood disorders following stroke would undoubtedly be improved by the consistent use of structured or semi-structured psychiatric interviews and standardized criteria for depression rather than a cutoff point on a rating scale.
Applicable diagnostic categories
In Chapter 7, I will discuss the controversy over the specificity of symptoms in patients with medical illness and alternative suggestions for diagnosis. This chapter,
Table 5.1. DSM-IV diagnostic criteria
Mood disorder due to a general medical condition, mood-incongruent delusions of hallucinations, or disorganized speech
The essential feature is a prominent and persistent mood that is judged to be due to the direct physiological effects of a general medical condition
Subtypes
I. With depressive features – predominant mood is depressed but full criteria for a major depressive episode are not met
II. With major depressive-like episode
A. At least five of the following symptoms present during at least a 2-week period.
At least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure
1. Depressed mood most of the day 2. Markedly diminished interest or pleasure 3. Significant weight loss or weight gain 4. Insomnia or hypersomnia
5. Psychomotor agitation or retardation 6. Fatigue or loss of energy
7. Feelings of worthlessness or excessive or inappropriate guilt 8. Diminished ability to think or concentrate
9. Recurrent thoughts of death
B. Distress or impairment in social, occupation, or other functioning C. Not bereavement
III. With manic features – predominant mood is elevated euphoric or irritable
IV. With mixed features – the symptoms of both mania and depression are present but neither predominates
however, will be devoted to the methodology and criteria used for diagnosis of poststroke depression or poststroke mania. The diagnostic category “mood disor-der due to stroke” has four subtypes: the first is mood disordisor-der due to stroke with depressive features; the second is with major depressive-like episode; the third is with manic features; and the fourth is with mixed features.
The first subtype (i.e., with depressive features) only requires the presence of a predominantly depressed mood but lacks full criteria for major depression. The obvious problem with this diagnosis and the reason we have not used it is that a patient with depressed mood alone and no other symptoms could be diagnosed using these criteria. The lack of specific depressive symptoms as well as number of symptoms required for diagnosis make this such a loose category as to not be use-able for research investigations. Similar problems arise in subtypes three and four (i.e., mood disorder due to stroke with manic features or mood disorder due to stroke with mixed features). There are no specific symptoms required for these diagnoses and patients with either an elevated or irritable mood and no other symptoms or patients with alternating depressed and irritable mood could be diagnosed with manic or mixed features using these criteria.
Due to these problems with diagnostic subtypes one, three, and four, we have recently been using DSM-IV research criteria for minor depression. Minor depres-sion is a term taken from research diagnostic criteria (RDC) (Feighner et al. 1972) to designate a subsyndromal form of major depression requiring at least two but less than five symptoms of major depression. Before DSM-IV had been published, we had used the symptom criteria, but not the duration criteria, from DSM-III dysthymic disorder for the diagnosis of minor depression. By using the term
“minor” rather than “dysthymic,” we tried to emphasize that these depressions were not long-term chronic depressions, but simply a less severe form of depressive disorder. The frequency of each of the symptoms for all acute stroke patients that we have examined with major or minor depression based on interviews using the PSE and DSM-IV symptom criteria are shown in Table 5.2. Spalletta et al. (2005) has recently reported on the same comparison among 50 patients with major depression, 62 with minor depression, and 88 non-depressed patients. Symptoms were elicited using the Structured Clinical Interview for DSM-IV patient (SCID-P).
Results showed that 2analysis found that the three groups differed significantly in the frequency of every symptom. After Bonferroni correction, only feelings of guilt failed to distinguish the three groups. Post-hoc analysis showed that patients with minor depression had significantly higher frequency of depressed mood, decreased interest, loss of energy, insomnia, and psychomotor disturbance compared with non-depressed patients.
The following are two case histories that demonstrate in Case A, major depres-sive disorder and in Case B, minor depresdepres-sive disorder.
43 Diagnosis of depression
44 Poststroke depression
Case A
When Dr. R. recounted her stroke, she remembered feeling, almost instanta-neously, an inability to understand what people were saying to her. She was in her early 50s and had just returned from a year of teaching and research abroad. As a distinguished historian, she had just completed a sabbatical year and was sought after by many universities. Although her father had died in his 50s of a heart attack, there was no family history of stroke. Her mother, a retired school teacher and hos-pital administrator was in good health in her 70s. It was a devastating symptom for someone whose life depended upon her ability to use language.
After the onset of her stroke, a series of other symptoms rapidly developed over the next few minutes. She was unable to move her right-side, she had lost sensation on that side of her body, she was unable to see in her right visual field, and she was unable to speak.
The first time I saw her was 3 years later. After 3 months in a rehabilitation hos-pital, her physical and speech recovery had been an enormous uphill battle. A year later she began having seizures. Two years after the stroke, while trying to walk, she fell down the stairs and sustained a traumatic brain injury including a subdural hematoma. She again was admitted to hospital and underwent surgery to evacuate the hematoma. Three years after the original stroke, although she was able to under-stand all but the most complicated sentences, she was unable to speak a coherent sentence, to read or to write.
Table 5.2. Frequency of DSM-IV symptoms
Initial Evaluation
A B C
Not Minor Major
depressed depression depression*
N (%) n 250 n 66 n 80 p 0.05
Depressed mood 2 (0.8) 63 (95.5) 80 (100.0) A B, A C Loss of interest 2 (0.8) 10 (15.2) 41 (51.3) A B, B C, A C Appetite/weight loss 48 (19.2) 16 (24.2) 49 (61.3) B C, A C
Insomnia 66 (26.4) 22 (33.3) 63 (78.8) A B, B C, A C
Psychomotor disturbance 101 (40.4) 44 (66.7) 74 (92.5) A B, B C, A C Loss of energy 89 (35.6) 33 (50.0) 68 (85.0) A B, B C, A C Feelings of guilt 36 (14.4) 16 (24.2) 47 (58.8) A B, B C, A C Decreased concentration 60 (24.0) 20 (30.3) 54 (67.5) B C, A C Suicidal ideation 2 (0.8) 2 (3.0) 18 (22.5) B C, A C
* All symptoms are significantly more frequent in major depression compared to no depression.
45 Diagnosis of depression
Depression began almost immediately after the stroke. She had recurrent episodes of depression that would last for many months. Eventually, the depression would begin to show some improvement, but then relapse. When I saw her, the depres-sion was readily evident. She had crying spells in my office, admitted to feelings of hopelessness and expressed feelings that life was not worth living. The profound-ness of her depression, however, was matched by her intense preoccupation with recovering her ability to read and write. For many months she had been focused on the idea that she was going to read and write again. Although this preoccupation with recapturing her lost identity was understandable, the obstacles were almost insurmountable. During this current episode of depression, for the first time, she had refused to go to speech therapy, lost interest in virtually all activities, became socially and emotionally withdrawn, lost interest in sex, felt like a worthless person, had difficulty concentrating, cried frequently, and felt there was no hope that she would ever recover.
Case B
At the time I first saw Mr. B., he had been depressed for 7 months. He was 59 years old and had been married for 34 years. He had been raised on a farm and still lived in a rural area. He had completed 2 years of college and worked for many years as a state auditor. He had suffered rheumatic heart disease as a child and at 39 had undergone electrical cardioversion to convert his heart from atrial fibrillation to normal sinus rhythm. As a result of the rheumatic heart disease, at age 50 he underwent open heart surgery for replacement of the mitral valve. After the sur-gery, he took anticoagulants and diuretic medications. His stroke occurred during sleep. He woke up disoriented to both time and place. He also noted ringing in his ears and difficulty seeing on the right side.
When I saw Mr. B., he did not look profoundly depressed but reported that his low mood began within a few days after the stroke. The depression was more severe on some days than it was on others but it had continued at some level for the past 7 months. Although the patient’s father had died 2 months after his stroke, his grief did not seem to be excessive or to be a cause of his prolonged depression. Mr. B.
reported symptoms of anxiety, tension, restlessness, worry, low energy, and loss of interest in activities that he previously enjoyed such as eating out or shopping. He also felt hopeless but did not report a change in his appetite, sleep, or ability to concentrate.
In addition to these symptoms of depression, Mr. B. was preoccupied by fears of having another stroke. Although he had returned to work, he was frightened that his performance would not be up to his supervisor’s standards and that he would be forced to take a disability retirement.
Mr. B.’s depression responded to psychotherapeutic treatment. Talking about his concerns, reassurance about his capacity to make appropriate decisions and
46 Poststroke depression
recognizing that he had an unfounded and exaggerated fear of complete loss of control of his life were enough to improve his depression without antidepressant medication.
Reliability and validity of diagnoses
The use of diagnostic criteria in psychiatry ultimately requires both demonstration of reliability as well as validity. We examined the use of a rating scale or a screening instrument, the Center for Epidemiological Studies-Depression Scale (CES-D), for diagnosis of poststroke depression compared with diagnoses based on standard PSE interview and DSM-III diagnostic criteria (Parikh et al. 1988). This study compared diagnoses in 80 patients who were interviewed using both the CES-D and the PSE with diagnosis based on DSM-III criteria. Using a cutoff point of 21 or greater on the CES-D, the specificity, sensitivity, and positive predictive value (PPV) of the CES-D for the diagnosis of major or minor depression was 94%
specificity, 72% sensitivity, and 85% PPV using the PSE interview and DSM-III criteria as the gold standard (Parikh et al. 1988). The optimal CES-D score, how-ever, was 16 which had a sensitivity of 90%, a specificity of 86%, a PPV of 80%, and a negative predictive value of 93%. The Spearman correlation between CES-D score and diagnosis of major, minor, or no depression was rho0.53, p 0.001 in-hospital. Thus, although an optimal number may be selected for an instrument to screen for poststroke depression, there are always patients with depression who are missed as well as patients without depression who are included in the sample.
Thus, the diagnosis of poststroke depression for both accuracy and consistency across the literature should be based on a structured or semi-structured interview and DSM-IV criteria.
Aben et al. (2002) recently examined the reliability and validity of diagnoses comparing self-rated and interview-rated scales for the diagnosis of poststroke depression utilizing 202 stroke patients examined 1 month after their first ever ischemic stroke. Determining optimal cutoff values, the sensitivity of the self-rated scales varied between 80% and 90% while the specificity was approximately 60%
compared with the gold standard of a structured interview (i.e., SCID-I-R) (First et al. 1996) and DSM-IV diagnostic criteria. The best rating scale was the observer rated Hamilton depression rating scale (HDRS) which had a sensitivity of 78.1%
and a specificity of 74.6%. Interestingly, the instruments had higher sensitivity and specificity in men compared with women. Thus, even using optimal cutoff scores, severity rating scales are not satisfactory substitutes for diagnostic criteria.
The issue of reliability for elicitation of symptoms using structured or semi-structured interviews is discussed in Chapter 7, Phenomenology and specificity of depressive symptoms. Once the symptoms are elicited, an algorithm can be
47 Diagnosis of depression
selected to determine whether the patient meets the DSM-IV diagnostic criteria for major or minor depression. We have used this technique for the investigation of the validity of distinguishing minor depression from major depression. The ques-tion which gives rise to this study is whether or not depressive disorder following stroke should be seen as a continuum or whether there are distinct forms of major and minor depression. The concept of subsyndromal depressive disorder has received increasing attention and numerous studies have provided validation for the dis-tinction between major and minor depression (Judd et al. 1998). The previously cited study by Spalletta et al. (2005) found that the frequency of decreased concen-tration, psychomotor disturbance decreased interest/pleasure, weight/appetite decrease, and suicidal ideation were all significantly greater in the 50 patients with poststroke major depression compared with 62 patients with minor depression.
Our validation study of major versus minor poststroke depression included 301 consecutive admissions to the University of Maryland Hospital in Baltimore with acute stroke (Paradiso and Robinson 1999). All patients who had a computed tomo-graphy (CT) or magnetic resonance imaging (MRI) verified single first ever lesion of either the left (n 64) or right (n 77) hemisphere that was compatible with their acute stroke symptoms were selected. Thirty patients (22%) had a DSM-IV diagnosis of minor depression, 24 (17%) had a DSM-IV diagnosis of mood disorder due to stroke with major depressive-like episode, and 87 patients (62%) were non-depressed.
Results demonstrated that a previous personal history of psychiatric disorder was significantly more frequent among patients with major depression (30.4%) versus minor depression (3.4%) (p 0.02). In addition, significantly more patients with major depression had lesions whose anterior border was less than 40% of the anterior-posterior (AP) distance on CT scan (83.3%) compared to the patients with minor depression (56.7%) (p 0.05). In addition, minor depression was significantly associated with a greater frequency of left hemisphere lesions and younger age when compared with control patients. Thirty-one of 87 control patients (35.6%) had a left hemisphere lesion compared with 20 of 30 (66.7%) with minor depression. Furthermore, the posterior border of the lesion was farther from the frontal pole in patients with minor depression compared with control subjects (i.e., 67.7% 22.0 SD of total AP measurement for minor depression ver-sus 54.3 21.0 SD for control subjects, p 0.02). No differences were found in lesion volume. In addition, there was a significant positive correlation between Ham-D and distance of both the anterior (Spearman’s rho 0.18, p 0.05), and posterior (Spearman’s rho 0.27, p 0.005) border of the lesion from the frontal pole for patients with minor depression, or no depression (Fig. 5.1).
When patients with major depression were compared to patients with minor depression, only 4 of 24 patients (16.7%) with major depression had posterior lesions (anterior border greater than 40% of AP distance) compared to 14 of 30
48 Poststroke depression
patients (43.3%) with minor depression (p 0.03). Finally, among patients with major depression, 17 of 24 (71%) also met DSM-IV symptom criteria for general-ized anxiety disorder (GAD), while only 7 of 84 (8%) of non-depressed patients, and 9 of 30 (30%) with minor depressions had associated GAD. The patients with minor depression had significantly more GAD diagnoses than control patients and significantly less GAD diagnoses than patients with major depression (p 0.006).
In addition to this study which was specifically aimed at distinguishing patients with minor depression from those with major depression, we will show in Chapter 14 that, in contrast to patients with major depression, patients with minor depression do not demonstrate a cognitive impairment related to depression.
Other diagnostic categories
Besides major and minor depression, the other diagnostic category, which may sometimes be applicable to patients with poststroke depression, is adjustment dis-order with depressed mood or adjustment disdis-order with mixed anxiety and depressed mood. These diagnoses using DSM-IV criteria are based on the exis-tence of depressed mood, tearfulness, or feelings of hopelessness with or without nervousness, worry, or jitteriness occurring within 3 months of the onset of an identified source of social stress. These depressive symptoms must be accompanied either by stress in excess of what would be expected from exposure to the stressor or by significant impairment in social or occupational functioning. The symptoms must not represent bereavement, exacerbation of a preexisting axis I or axis II dis-order, or be present for more than 6 months after termination of the stressor.
0 5 10 15 20 25 30
0 20 40 60 80 100 120
Distance of posterior border of lesion from frontal pole
Hamilton score
r 0.27, p 0.005
Figure 5.1 Scatterplot of the relationship between the distance of the posterior border of the lesion from the frontal pole (as a percentage of the overall A–P distance) and the severity of depression symptoms as measured by the Ham-D among patients with minor poststroke depression or no mood disorder (r 0.27, p 0.005) reprinted with permission from Paradiso and Robinson (1999).
If the psychosocial stressor may be seen as the loss of job or social role which may result from the cognitive or physical impairments produced by stroke, this diagno-sis may be appropriate. Several investigators have used this category for diagnosing patients with depression following stroke (House et al. 1991). The diagnosis of adjustment disorder does not require any specific symptoms. Furthermore, judg-ments about whether the distress is in excess of what would be expected or whether the depression per se has led to social or occupational impairment are often diffi-cult determinations to make in patients with physical and mental impairments fol-lowing stroke. Another difficult judgment is when the stressor is gone. Since we know that depressions last more than 6 months, the stressor would have to be seen as extended beyond the acute stroke period, but how long? The lack of specificity of symptomatology and the ambiguity of defining criteria make this an unappeal-ing research diagnosis. Most researchers, therefore, have chosen to distunappeal-inguish major depression and frequently minor depression associated with stroke. I believe that adjustment disorders or dysthymic disorders with duration of depressive symptoms for greater than 2 years are only rarely applicable to patients with stroke mood disorders. The consistency of diagnosis would be improved if post-stroke depression diagnoses were restricted to major or minor depressive disorder.
In summary, the diagnosis of poststroke depression should be based on the use of a structured or semi-structured psychiatric interview to elicit symptoms of depres-sion and the DSM-IV diagnostic criteria for mood disorder due to stroke with major depressive like episode or minor depression. We have demonstrated that there are significant differences between patients with major depression and minor depression in the frequency of personal history of psychiatric disorder as well as distance of the anterior border of the lesion from the frontal pole and Spalletta has shown differences in the frequency of five of the nine symptoms of major depres-sion. Patients with minor depression during the acute poststroke period tend to have posterior lesions of the left hemisphere while patients with major depression tend to have anterior left hemisphere lesions. In addition, depression related cog-nitive impairment is associated with major depression but not minor depression.
Although additional studies will be needed to validate the diagnosis of both major and minor depression in the stroke population, at least the process has begun of demonstrating that there are clinical variables, symptom frequency, and patholog-ical variables which distinguish major depression from minor depression.
Ultimately the validation of diagnostic categories requires that a specific etiol-ogy, pathophysiology of the disorder be identified. Since this level of validation has not been established for any of the psychiatric disorders, studies aimed at showing differences among diagnostic criteria in terms of clinical presentation, longitudinal course, clinical correlates, pathological correlates, and response to treatment have been used to validate diagnostic categories in psychiatry. Several investigations 49 Diagnosis of depression
50 Poststroke depression
have been able to demonstrate differences between major and minor depression as outlined in this chapter and have provided some initial validation for the impor-tance of distinguishing major and minor depression.
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