Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances.

OBJECTIVE: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. METHOD: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. RESULTS: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. LIMITATION: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. CONCLUSIONS: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. CLINICAL IMPLICATIONS: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.

Failure to demonstrate parent-of-origin effect in transmission of bipolar II disorder.

BACKGROUND: Parent-of-origin effect (POE) is suggested in transmission of bipolar disorder. Bipolar II disorder (BPII) should be considered separately. METHODS: The gender difference of transmitting parents, prevalence rate in children, and age at onset of patients in relation to the sex of the transmitting parent, were examined in 220 BPII patients. RESULTS: No evidence suggesting involvement of POE was found. CONCLUSION: POE is not involved in transmission of BPII. LIMITATION: Number of subjects is not sufficient. Rate of interviewed subjects differs between mothers and fathers. CLINICAL RELEVANCE: Female BPII patients do not transmit the disease more often than male patients.

Quantitative analysis of leukocyte mitochondrial DNA deletion in affective disorders.

Mutations in mitochondrial DNA (mtDNA) are implicated in the pathophysiology of affective disorders. To determine whether the 4977-base-pair deletion in mtDNA is more frequent in affective disorders, we quantitated the concentration of this deletion in leukocyte mtDNA in 34 probands with affective disorders (20 bipolar and 14 unipolar) and 20 controls. We found no significant difference in the quantitative ratio of deletion to wild-type mtDNA between patients and controls. One patient with unipolar depression and 1 of 2 patients previously reported as having a large quantity of the deleted mtDNA did have a markedly high ratio; however, the deletion did not segregate with the disease in these two families. These results do not support a hypothesis that the 4977-base-pair deletion plays an important role in the pathophysiology of affective disorders.

All roads lead to depression: clinically homogeneous, etiologically heterogeneous.

Manias, and particularly depressions, are syndromes not disease. Considerable data support the fact that depressions, though similar clinically, are of heterogeneous etiologies. We can separate depressions generally into those that are endogenous/psychotic and those that occur in the context of marked emotional instability. Familial pure depressive disease is a specific example of the former, depression spectrum diseases a specific example of the latter. These are separable on the basis of personality, clinical, follow-up, familial and treatment variables.

The effect of gender and age at onset of depression on mortality.

BACKGROUND: Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. METHOD: Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. RESULTS: After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. CONCLUSION: These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness.

Lithium and recurrence in a long-term follow-up of bipolar affective disorder.

BACKGROUND: Though previous studies have clearly shown that lithium affords prophylaxis in bipolar affective disorder, these studies have not demonstrated the persistence of this prophylactic effect beyond the first year of recovery. METHODS: One hundred and eighty-one patients with bipolar affective disorder recovered during 5 years of semi-annual follow-up. After 8 weeks of recovery, 139 were taking lithium prophylaxis and 42 were not. Analyses used drug status (lithium v. no-lithium) as a censoring variable to compare these two groups by interval-specific probabilities of recurrence. RESULTS: Recurrence was initially less likely in the lithium group but interval-specific probabilities of recurrence did not consistently favour either group after the first 32 weeks of recovery. CONCLUSIONS: Biases in treatment decisions may have both reduced the size and altered the specificity of the lithium effects seen here. Nevertheless, the apparent transience of lithium prophylactic effects is unexplained and may reflect important, physiological differences between relapse and recurrence. This possibility invites a controlled lithium discontinuation study, with gradual taper, of patients who have had at least 8 months of sustained euthymia.

Parent-of-origin effect in transmission of bipolar disorder.

Recently, possible involvement of a parent-of-origin effect in the transmission of bipolar disorder has been suggested. We examined the possible contribution of parent-of-origin effect by using data from a large family and family history study of bipolar patients in the Collaborative Depression Study. In 276 probands with bipolar I disorder, family histories were examined using three diagnostic criteria: 1) bipolar I disorder, 2) bipolar I or bipolar II disorder, and 3) bipolar disorders or recurrent unipolar depression for parents and siblings. An excess of affected mothers was not observed when unipolar depression was excluded. Age-at-onset was significantly lower in probands having a father with bipolar disorders or recurrent unipolar depression than in probands with an affected mother. This difference was not observed when unipolar depression was excluded. There was no significant difference of prevalence rate in children of affected mothers and those with affected fathers. These data do not support the contribution of parent-of-origin effect in the transmission of bipolar disorder.

Depression spectrum disease, I: The role of gene-environment interaction.

OBJECTIVE: This study used an adoption study design to separate genetic from environmental factors in the etiology of depression spectrum disease, a type of major depression characterized by families in which male relatives are alcoholic and females are depressed. The genetic etiology hypothesis of depression spectrum disease proposes that an alcoholic genetic diathesis predisposes to depression in females but alcoholism, not depression, in males. METHOD: The study examined 197 adult offspring (95 male and 102 female) of alcoholic biological parents and used logistic regression models to determine the contribution to major depression in male and female adoptees that could be explained by the genetic alcoholic diathesis combined with an environmental factor that was characterized by psychiatrically or behaviorally disturbed adoptive parents. RESULTS: Major depression in females was predicted by an alcoholic diathesis only when combined with the disturbed adoptive parent variable. The same regression model failed to predict depression in males. Other possible environmental confounding factors contributing to an increased chance of depression were found in females: fetal alcohol exposure, age at the time of adoption, and a family with an adopted sibling who had a psychiatric problem. These variables did not diminish the significance of the prediction of depression with the alcohol genetic diathesis and disturbed parent model. CONCLUSIONS: The results show that a genetic factor is present for which alcoholism is at least a marker, and which exerts its effect in women as a gene-environment interaction leading to major depression. This finding suggests that an important etiologic factor in depression spectrum disease is gene-environment interaction.

Importance of psychotic features to long-term course in major depressive disorder.

OBJECTIVE: Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessments 1 year or less after the initial evaluation. However, the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term. METHOD: The 787 patients described here entered the study as they sought treatment at one of five academic medical centers; they had either RDC major depressive disorder or schizo-affective depression (other than the mainly schizophrenic subtype) and completed at least 6 months of follow-up. Of these, 144 (18.3%) had psychotic depression as defined here. Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years. RESULTS: Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years. Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes, but nonpsychotic episodes among previously psychotic individuals were relatively brief. Intervals between episodes were significantly shorter for patients who had ever been psychotic. CONCLUSIONS: Together with evidence that psychotic features are highly recurrent, these data show 1) that psychotic features denote a lifetime illness of greater severity and 2) that within individuals, psychotic features may emerge in only the more severe episodes.

Familial alcoholism in manic-depressive (bipolar) disease.

A previous analysis found a relatively high rate of alcoholism in a cohort of bipolar I subjects, and a trend for increased rates of alcoholism in relatives of subjects with both bipolar I disorder and alcoholism, compared to relatives of subjects with bipolar I disorder and no alcoholism. The sample of subjects with bipolar I disorder has been enlarged through continued follow-up, permitting new analyses to address the association and heritability of bipolar I disorder with alcoholism. Probands with bipolar I disorder were followed for 10 years as part of the NIMH Collaborative Depression Study. The rate of alcoholism in relatives of probands with both bipolar I disorder and alcoholism was compared to the rate of alcoholism in relatives of probands with bipolar disorder and no alcoholism. The prevalence of alcoholism in relatives of subjects with bipolar I disorder was compared to the rate of alcoholism in relatives of control subjects. Relatives of probands with bipolar I disorder showed a higher rate of alcoholism than relatives of controls. Relatives of probands with bipolar I disorder and alcoholism showed a higher rate of alcoholism than relatives of probands with bipolar I disorder without alcoholism. These data suggest that familial alcoholism may contribute to a vulnerability to bipolar I disorder, and that there is a shared heritability for the two disorders.

Schizophrenia and affective disorder--distinct entities or continuum?: an analysis based on a prospective 6-year follow-up.

The purpose of this study was to determine whether the preponderance of data support a continuum hypothesis of the psychoses or a concept of separate, autonomous illnesses. Patients (N = 70) were hospitalized for nonmanic psychoses, given structured interviews and a dexamethasone suppression test (DST), and diagnosed according to the Research Diagnostic Criteria (RDC). Patients were then evaluated at 1 year and 6 years with a structured interview. Diagnoses were made at three points of time: intake, 1 year, and 6 years. The patients were divided into groups that had a consistent (over the three points) set of affective disorder diagnoses (affective disorder or schizoaffective disorder, mainly affective [AD group]) and those that had a consistent set of schizophrenic diagnoses (schizophrenic or schizoaffective disorder, mainly schizophrenic [S group]). A third group (inconsistently diagnosed) consisted of subjects who at one point were diagnosed in the AD group and at another in the S group. A series of discriminant function analyses suggested that the AD group differs widely from the S group; and the inconsistently diagnosed group most closely resembled the AD group. The family background of the inconsistent group was similar to that of the AD group. The DST and outcome showed that the inconsistent group was more like the AD group than the S group. Using the characteristics of the medical model-clinical picture, outcome, laboratory tests, and family history-the group that was inconsistent with regard to diagnosis over time appeared similar to the AD group. Taking the follow-up evaluation into account, the data favor the possibility that patients who have a variable clinical diagnosis over time do not suffer from schizophrenia.

Effect of ECT on mortality and clinical outcome in geriatric unipolar depression.

BACKGROUND: Recent reports have called into question the safety and effectiveness of electroconvulsive therapy (ECT). METHOD: To investigate these claims, the effects of ECT on clinical outcomes were examined as part of a retrospective, naturalistic study of 192 geriatric patients consecutively admitted between 1980 and 1987 to a large midwestern tertiary care center for the treatment of depression. Data were analyzed by a variety of parametric and nonparametric methods including ANOVA and survival analysis. RESULTS: Patients who received ECT (N = 108) were more likely to exhibit psychomotor retardation and to have had prior courses of ECT than those who did not receive ECT (N = 84). Furthermore, despite the absence of differences in the overall rate or severity of medical comorbidity, patients receiving ECT were more likely to be alive at follow-up and to demonstrate greater clinical improvement than those treated only with pharmacotherapy. CONCLUSION: These results confirm previous studies demonstrating the superior efficacy of ECT as compared with conventional pharmacotherapy treatment in patients hospitalized with depression and document its safety in long-term follow-up.

Characteristics and significance of untreated major depressive disorder.

OBJECTIVE: This study sought to describe the characteristics and consequences of untreated major depressive disorder. METHOD: As part of a family study of probands with major affective disorders, raters assessed 3,119 first-degree relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these individuals were reassessed 6 years later, 547 had experienced episodes of major depressive disorder in the interval. Those who had sought any form of treatment for any episode of major depressive disorder in the interval were compared, by baseline demographic characteristics and clinical features of their worst episodes of major depressive disorder, to those who had not. Individuals who had had untreated major depressive disorder were then compared, by changes in socioeconomic status and by levels of psychosocial impairment at follow-up, to a matched group with no major depressive disorder in the interval. RESULTS: The worst episodes of 313 treated individuals, compared to those of 234 untreated individuals, were characterized by older age, symptoms of the endogenous subtype, longer durations, and the presence of disruption in role function. Each of these factors contributed independently to the distinction between treated and untreated episodes. Untreated individuals experienced significant psychosocial impairment on follow-up but did not show the economic disadvantages shown elsewhere for probands who began follow-up as they sought treatment at tertiary medical centers. CONCLUSIONS: These data suggest that illness characteristics and age determine the decision to seek treatment for major depressive disorder. Untreated depression is apparently associated with long-standing psychosocial difficulties but not with serious economic consequences.

Familial depression versus depression identified in a control group: are they the same?

Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment. This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study. Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands. Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression. They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study. In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands. Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls. Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations.

Delusional infestation. The interface of delusions and hallucinations.

Delusional infestation represents a unique subtype of the delusional disorder category. This article presents the phenomenology, etiology, and treatment of delusional infestation. This article also reviews historical and theoretical attempts to distinguish tactile sensory phenomena as either hallucinations or delusions.

A family study of manic-depressive (bipolar I) disease. Is it a distinct illness separable from primary unipolar depression?

OBJECTIVE: To determine whether bipolar I illness is autonomous or part of a multifactorial continuum with unipolar depression. In this study, we compare familial bipolar I illness and depression among three groups: probands with bipolar I disorder; probands with primary unipolar disorder; and controls. We also examine a continuum of severity between psychotic and nonpsychotic patients with bipolar I disorder. Considerable data suggest that bipolar I illness is distinct from unipolar illness as regards epidemiology, familial psychiatric illness, course, response to treatment, and biologic findings. METHOD: Probands were separated into bipolar I and primary unipolar depressive groups. Personally interviewed family members of these patients were compared on variables of bipolar illness or schizoaffective mania and unipolar or schizoaffective depression. A personally examined control group was compared with the relatives of the two proband groups. Similar analyses were performed using data obtained by a systematic family history method. For the same familial variables, psychotic and nonpsychotic manic probands were compared. RESULTS: Familial mania is more frequent in families of patients with bipolar disease than in controls or in families of patients with primary unipolar disorder. The latter two groups did not differ in amount of mania. Unipolar depressive illness or schizoaffective depression was higher in families of probands with bipolar and unipolar disorder than in controls. Probands with bipolar disease separated into those who had psychotic symptoms (including schizoaffective mania) and no psychotic symptoms did not differ from each other in risk for familial mania or depression. CONCLUSIONS: Bipolar I illness is a separate illness from primary unipolar illness because of an increase in familial mania. Patients with primary unipolar disease and controls show the same amount of familial mania. Lack of an increase in familial illness according to the severity of bipolar disease is against an affective continuum.

Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction.

OBJECTIVE: This 5-year follow-up study was designed to explore the factors that might lead to alcoholism in patients with bipolar disorder. METHOD: The authors studied patients with bipolar illness (70 with alcoholism and 161 without), their relatives, and a comparison group composed of relatives' acquaintances. All were evaluated with versions of the Schedule for Affective Disorders and Schizophrenia, and diagnoses were made according to the Research Diagnostic Criteria. Thirty of the bipolar alcoholic patients whose affective disorder was primary were also compared with 34 whose alcoholism was primary. RESULTS: Alcoholism was more frequent in the bipolar patients than in the comparison subjects. There no significant differences between the alcoholic and nonalcoholic bipolar patients in family history of alcoholism or affective disorders, suggesting that bipolar illness with alcoholism is not explicable by a family history of alcoholism and that the alcoholism seen in bipolar illness is dissimilar to alcoholism as a primary disorder. Alcoholism associated with bipolar illness was more likely to remit than primary alcoholism. There was no significant difference in family history between the patients with primary alcoholism and those with primary bipolar disorder. The patients with primary alcoholism had significantly fewer episodes of affective disorder during followup, suggesting that their type of bipolar illness was less severe and may have needed the added insult of alcoholism to make it manifest. CONCLUSIONS: The study supports the idea that not all alcoholism is primary with a corresponding familial diathesis. Rather, alcoholism associated with bipolar disorder is often a secondary complication.

Recurrently situational (reactive) depression: a study of course, phenomenology and familial psychopathology.

Probands with non-bipolar major depressive disorder (MDD) were grouped according to the consistency across episodes with which depression appeared to arise from situational factors. Situational depression showed significant diagnostic stability across the second and third recurrences in a 10-year follow-up. The relatives of recurrently situational probands had higher neuroticism scores, higher lifetime rates of MDD and, when depressed, fewer endogenous symptoms than did the relatives of non-situational probands. This study joins two others in finding an association between stress-related depression and high familial loadings for MDD. It also illustrates the value of diagnostic consistency across episodes as a means of refining groups for the study of diagnostic subtypes.