Understanding depression.
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Biomedical subjects
Publications and source records attributed to P H Wender.
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BACKGROUND: Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness. METHODS: We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample"). RESULTS: In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls. CONCLUSIONS: This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.
We investigated the risk for substance abuse in the biological relatives of adoptees with affective illness, controlling for potential confounds, and additionally assessed risk by probands' and relatives' gender. Our sample consisted of 67 index adoptees with affective illness, matched control adoptees, and their biological and adoptive relatives. Both affective illness and substance abuse were more common in the biological relatives of affectively ill adoptees than in controls' relatives. Affective illness was more common than substance abuse among female index biological relatives, with the opposite pattern observed among male relatives.
A visual word identification task was used to measure the type of selective attention that occurs spontaneously when there are multiple stimuli, all potentially relevant, and insufficient time to process each of them fully. This task presents two words simultaneously, one above the other, for 200 ms, and periodically requires the subject to identify either the upper or the lower word. We tested schizophrenic patients, manic-depressive patients, and normal controls under a baseline divided attention condition with no predictability and then introduced a degree of predictability into the upper location that normally results in selective attention to the lower nonpredictable location. In both the divided attention and the selective attention conditions, the schizophrenic group was just as accurate in identifying words as the other two groups, indicating no deficit in the rate of information processing. However, spontaneous selective attention under conditions of predictability was abnormal in the schizophrenic patients: They paid more attention to the predictable than to the nonpredictable source of information, consequently processing different, not less, information than normal subjects. Abnormal values on a ratio measure of selective attention occurred in 85% of the schizophrenic patients compared with only 30% of the manic-depressives and 20% of the normal subjects.
The authors treated 19 adults with attention-deficit hyperactivity disorder with an open trial of bupropion. These patients had received maintenance stimulant medication or monoamine oxidase inhibitors for an average of 3.7 years. Fourteen of the patients experienced moderate to marked benefit from bupropion; ten of these patients chose to continue bupropion rather than their former medication. These results suggest that bupropion may be an alternative to stimulants in treating some adults with attention-deficit hyperactivity disorder.
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To elucidate the role of catecholamines in attention deficit disorder, the authors conducted an open 8-week trial of L-tyrosine in 12 adults with attention deficit disorder, residual type. Eight showed marked to moderate clinical response in 2 weeks; at 6 weeks these eight developed tolerance, suggesting that L-tyrosine is not useful in attention deficit disorder, residual type.
To investigate the contribution of genetic and environmental factors in the etiology of mood disorders, a study was initiated to examine the frequency of psychiatric disorders in the biological and adoptive relatives of adult adoptees with mood disorders and in matched normal adoptees. Psychiatric evaluations of the relatives were made on the basis of independent blind diagnoses based on mental hospital and other official records. Analysis of the data showed an eightfold increase in unipolar depression among the biological relatives of the index cases and a 15-fold increase in suicide among the biological relatives of the index cases. These data demonstrate a significant genetic contribution to unipolar depression and suicide. They fail to disclose a significant contribution of family-associated transmission in the genesis of the mood disorders.
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Nineteen patients meeting the criteria for attention deficit disorder, residual type (adult hyperactivity), were given a 2-week double-blind crossover of DL-phenylalanine versus placebo. Thirteen subjects completed the study; the mean global rating of improvement approached significance as compared with placebo. A significant improvement was noted on mood and mood lability. The phenylalanine responders were then continued on open drug, but lost all positive benefits within 3 months. A later open trial of L-phenylalanine produced no clinical effect.
Thirty-seven adult patients meeting the Utah criteria for attention deficit disorder, residual type, were entered into a double-blind crossover trial of methylphenidate and placebo. A moderate-to-marked therapeutic response occurred in 21 (57%) of the patients while receiving methylphenidate and in four (11%) while receiving placebo, a highly significant difference statistically and clinically. The responding patients showed significant improvement in the following areas: attentional difficulty, motor overactivity, affective lability, and impulsivity. The diagnosis of attention deficit disorder, residual type, should be considered in patients with prominent complaints of impulsivity, restlessness, emotional lability, and hot temper who do not suffer from schizophrenia or major mood disorder and do not have symptoms of schizotypal or borderline personality disorders.
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Following the hypothesis that attention deficit disorder in adults (attention deficit disorder, residual type; ADD, RT), as well as in children, is associated with decreased central dopaminergic activity, the authors measured lumbar cerebrospinal fluid monoamine metabolites in a group of adults with ADD, RT and matched control subjects. Patients were then entered into a double-blind, placebo-controlled trial of methylphenidate. It was predicted that the patients would have lower levels of homovanillic acid (HVA), the major dopamine metabolite in humans. Patients who had a significant response to methylphenidate showed a trend in this direction. Nonresponding patients had significantly higher levels of HVA than controls.
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Twenty-two patients who met the Utah criteria for attention deficit disorder, residual type (hyperactivity, minimal brain dysfunction in adults) received an open trial of pargyline (Eutonyl). Of these 22 patients, 13 (59%) showed a moderate to marked therapeutic response. Clinically useful features of pargyline in the treatment of attention deficit disorder, residual type are that its duration of action is greater than 24 hours and that it has not been abused. Pargyline inhibits monoamine oxidase, type B, and its therapeutic efficacy is compatible with the hypothesis that decreased phenethylaminergic function, dopaminergic function, or both play a role in the etiology of the disorder.