A family study of DSM-III-R schizoaffective disorder, depressive type, compared with schizophrenia and psychotic and nonpsychotic major depression

OBJECTIVE: To assess the validity of DSM-III-R schizoaffective disorder, the authors explored the morbid risks for schizophrenia and major affective disorders in the first-degree relatives of patients with schizoaffective disorder and relevant other diagnoses. METHOD: In addition to patients with DSM-III-R schizoaffective disorder, depressive type (N = 21), the probands included patients with mood-incongruent psychotic depression (N = 22), mood-congruent psychotic depression (N = 19), nonpsychotic depression (N = 27), or schizophrenia (N = 28) and normal subjects (N = 18). The patients were consecutively recruited from the outpatient facilities of a university psychiatry department; the normal subjects were students and nurses. All probands were directly interviewed, with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version (SADS-L), by a psychiatrist blind to information about relatives. Consenting relatives were directly interviewed, with the SADS-L, by two psychiatrists blind to the probands' diagnoses. The direct interview was supplemented--or replaced, when an interview was not possible (24%)--by family history data from all available sources. Morbid risks in relatives were calculated according to the Weinberg method. RESULTS: The relatives of the schizoaffective patients had almost the same risk for schizophrenia as the relatives of the schizophrenic patients. In the relatives of the patients mood-incongruent psychotic depression, the morbid risk for major affective disorders was about one-half that of the relatives of the patients with mood-congruent psychotic depression and one-third that of the relatives of the patients with nonpsychotic depression, but these differences did not reach statistical significance. CONCLUSIONS: These results suggest that DSM-III-R schizoaffective disorder is close to schizophrenia and largely corresponds to mainly schizophrenic schizoaffective disorder in the Research Diagnostic Criteria, whereas DSM-III-R mood-incongruent psychotic depression is probably quite heterogeneous and should be studied further.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Sensitivity of psychiatric diagnosis based on the best estimate procedure.

OBJECTIVE: A "best estimate" diagnosis is one made by expert clinicians on the basis of diagnostic information from direct interview conducted by another clinician plus information from medical records and from reports of family members. The authors address the question of whether the best estimate procedure can enhance the classification of psychiatric diagnoses of subjects who are interviewed directly. METHOD: Four hundred seventy-five subjects were interviewed directly: 201 opiate-addicted probands who sought treatment from a university-based clinic and 274 of their spouses and/or first-degree relatives. Subjects were interviewed by trained clinical assessors using the Schedule for Affective Disorders and Schizophrenia and classified according to Research Diagnostic Criteria. Two psychologists independently diagnosed the same subjects by applying the best estimate procedure. Lifetime rates of major and minor depressive disorder, antisocial personality, alcoholism, and drug abuse were calculated. The rates of diagnoses made on the basis of direct interviews alone were compared with the rates of diagnoses made according to the best estimate procedure. RESULTS: Higher rates of diagnoses of all four disorders were made when the best estimate procedure was applied than when direct interview alone was used; the best estimate procedure also resulted in a minimal rate of false positives. CONCLUSIONS: The higher rate of diagnoses based on the best estimate procedure may represent an enhancement in the accuracy of psychiatric diagnoses or an increase in erroneous diagnoses. The authors consider the second possibility less likely.     

Family study of chronic depression in a community sample of young adults

OBJECTIVE: The validity of the distinctions between dysthymic disorder, chronic major depressive disorder, and episodic major depressive disorder was examined in a family study of a large community sample of young adults. METHOD: First-degree relatives (N=2,615) of 30 probands with dysthymic disorder, 65 probands with chronic major depressive disorder, 313 probands with episodic major depressive disorder, and 392 probands with no history of mood disorder were assessed by using direct interviews and informant reports. RESULTS: The rates of major depressive disorder were significantly greater among the relatives of probands with dysthymic disorder and chronic major depressive disorder than among the relatives of probands with episodic major depressive disorder, who in turn exhibited a higher rate of major depressive disorder than the relatives of probands with no history of mood disorder. The relatives of probands with dysthymic disorder had a significantly higher rate of dysthymic disorder than the relatives of probands with no history of mood disorder, and the relatives of probands with chronic major depressive disorder had a significantly higher rate of chronic major depressive disorder than the relatives of probands with no history of mood disorder. However, the relatives of the three groups of probands with depression did not differ on rates of dysthymic disorder and chronic major depressive disorder. CONCLUSIONS: Chronic depression is distinguished from episodic depression by a more severe familial liability. This familial liability may contribute to the more pernicious course of chronic depression.     

Familial alcoholism in primary unipolar major depressive disorder

OBJECTIVE: Some studies have suggested relationships between depression in probands and alcoholism in relatives. Other studies have not, but some of these have used inappropriate control groups or failed to divide probands by sex. METHOD: The present study controlled for sex of probands and used several comparison groups to further explore the familial relationship between depression and alcoholism. Diagnoses for 723 directly interviewed relatives of 326 probands with primary unipolar depression were compared to diagnoses in 469 control subjects chosen by an acquaintanceship method to demographically resemble the relatives of affective disorder probands. Diagnoses in the uninterviewed relatives of both control and depressed subjects were used for comparisons as well. RESULTS: Results indicated higher rates of alcoholism in the families of depressed women but not in the families of depressed men. CONCLUSIONS: This familial association between alcoholism and depression may be the result of either genetic or environmental factors or an interaction between the two.     

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.     

Familial rates of affective illness in Sardinia with special reference to schizoaffective disorder

Summary Familial rates of psychiatric disorders were studied in southern Sardinia and showed an increase in relatives of probands with the following research diagnostic criteria (RDC) diagnoses: normal, unipolar depression, schizoaffective depressive, schizoaffective bipolar, bipolar with mania and bipolar with hypomania. A significantly higher risk for bipolar schizoaffective disorder was observed in relatives of bipolar schizoaffectives compared with relatives of normal probands.Supported by a grant from Regione Autonoma della Sardegna, Assessorato all'Igiene e Sanità     

Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients

To evaluate whether probands from a clinical sample diagnosed as having DSM-III schizotypal and/or paranoid personality disorder have a familial relationship to the schizophrenia-related disorders, the morbid risk for schizophrenia-related disorders and other psychiatric disorders were evaluated in the first-degree relatives of patients with schizotypal and/or paranoid personality disorder and compared with the corresponding risk for these disorders in the first-degree relatives of patients with other non-schizophrenia-related personality disorders. The morbid risk for all schizophrenia-related disorders, and specifically for schizophrenia-related personality disorders, was significantly greater among the relatives of the probands with schizotypal and/or paranoid personality disorder than among the relatives of probands with other personality disorder. The morbid risk for other psychiatric disorders did not differ significantly between the first-degree relatives of the schizotypal/paranoid personality disorder and the other personality disorder control proband samples. These results suggest a specific familial association between schizophrenia-related disorders, particularly schizophrenia-related personality disorders, and clinically diagnosed schizotypal patients.     

Psychiatric disorders in relatives of probands with opiate addiction

Previous research has documented high rates of major depression and antisocial personality in opiate addicts. This study was designed to investigate the relationship of dual diagnosis in opiate-addicted probands to family history of psychiatric disorders and substance use disorders in biological relatives. Psychiatric disorders and substance use disorders were evaluated using direct interview and family history in a sample of 877 first-degree relatives of 201 opiate addicts and 360 relatives of 82 normal controls. Results indicate that (1) compared with relatives of normal subjects, opiate addicts' relatives had substantially higher rates of alcoholism, drug abuse, depression, and antisocial personality; (2) relatives of depressed opiate-addicted probands had elevated rates of major depression and anxiety disorders but not of other disorders, suggesting the validity of subtyping opiate addicts by the presence or absence of major depression; and (3) in contrast, relatives of antisocial opiate addicts had rates of disorders that were not significantly different from those of relatives of opiate addicts without antisocial personality. Implications of these findings for the classification and treatment of substance abuse are discussed.     

Avoidant personality disorder is a separable schizophrenia-spectrum personality disorder even when controlling for the presence of paranoid and schizotypal personality disorders The UCLA family study

It is unresolved whether avoidant personality disorder (APD) is an independent schizophrenia (Sz)-spectrum personality disorder (PD). Some studies find APD and social anxiety symptoms (Sxs) to be separable dimensions of psychopathology in relatives (Rels) of schizophrenics while other studies find avoidant Sxs to be correlated with schizotypal and paranoid Sxs. Rates of APD among first-degree Rels of Sz probands, attention-deficit/hyperactivity disorder (ADHD) probands, and community control (CC) probands were examined. Further analyses examined rates when controlling for the presence of schizotypal (SPD) and paranoid (PPD) personality disorders, differences in APD Sxs between relative groups, and whether APD in Rels of Szs reflects a near miss for another Sz-spectrum PD. Three hundred sixty-two first-degree Rels of Sz probands, 201 relatives of ADHD probands, and 245 Rels of CC probands were interviewed for the presence of DSM-III-R Axis I and II disorders. Diagnoses, integrating family history, interview information, and medical records, were determined. APD occurred more frequently in Rels of Sz probands compared to CC probands (p<0.001) and also when controlling for SPD and PPD (p<0.005). Two Sxs of APD were most characteristic of the Rels of Sz probands: "avoids social or occupational activities..." and "exaggerates the potential difficulties..." 65% of the Rels of Sz probands who had diagnoses of APD were more than one criterion short of a DSM-III-R diagnosis of either SPD or PPD. This indicates that APD is a separate Sz-spectrum disorder, and not merely a sub-clinical form of SPD or PPD.     

Personality disorder in the families of depressed, schizophrenic, and never-ill probands

In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never-ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders.     

A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands

BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability. DESIGN: Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account. RESULTS: Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.     

Familial transmission of schizotypal and borderline personality disorders

The authors determined the risk for psychiatric disorders in the first-degree relatives of 36 probands with schizotypal personality disorder (13 definite, 23 probable), 17 probands with borderline personality disorder (two definite, 15 probable), and 90 normal control probands. The relatives of probands with schizotypal personality disorder without a concurrent diagnosis of borderline personality disorder had a significantly greater risk for schizotypal personality disorder than the relatives of normal control probands, borderline probands, or schizotypal probands with coexisting borderline personality disorder. The relatives of borderline probands had a significantly greater risk for definite and probable borderline personality disorder than the relatives of normal control probands.     

A family study of pathological gambling

The cause of pathological gambling (PG) is unknown. The current study was conducted to determine whether PG is familial, and to examine patterns of familial aggregation of psychiatric disorder. To that end, 31 case probands with DSM-IV PG and 31 control probands were recruited and interviewed regarding their first degree relatives (FDRs). Available and willing FDRs were directly interviewed with structured instruments of known reliability, and best estimate final diagnoses were blindly assigned for 193 case and 142 control relatives over age 18 years. The results were analyzed using logistic regression by the method of generalized estimating equations. The lifetime rates of PG and "any gambling disorder" were significantly greater among the relatives of case probands (8.3% and 12.4%, respectively) than among the control relatives (2.1% and 3.5%, respectively) (OR=3.36 for "any gambling disorder"). PG relatives also had significantly higher lifetime rates of alcohol disorders, "any substance use disorder," antisocial personality disorder (ASPD), and "any mental disorder". "Any gambling disorder," alcohol disorder, and "any substance use disorder" remained significant after a conservative Bonferroni correction. Interestingly, PG families were significantly larger than control families. We conclude that gambling disorders are familial and co-aggregate with substance misuse. The data are also suggestive that PG co-aggregates with ASPD. Further research on the heritability of PG is warranted.     

Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands

Objective: This study examined the comorbidity of obsessive–compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. Method: This study assessed the lifetime prevalence of MDD in 141 first‐degree relatives (FDR) and 452 second‐degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best‐estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Results: Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). Conclusions: MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Mental disorders in first-degree relatives of schizophrenics

A total 215 first-degree relatives of 88 twin probands with schizophrenia, mood disorders and nonaffective psychoses were studied. The twins' parents and siblings were personally interviewed with structured diagnostic instruments and diagnosed in accordance with DSM-III-R criteria. The first-degree relatives were interviewed by interviewers who were blind to the twins' diagnoses. Schizophrenia and schizotypal personality disorder were significantly more frequent in first-degree relatives of schizophrenic twins. Respectively, anxiety and mood disorders were significantly more prevalent among the parents and siblings of probands with mood disorders. Schizophrenic spectrum disorders were significantly more common in the families of schizophrenic probands compared with relatives of mood disorder probands, thus confirming a relationship between schizophrenia and schizophrenic spectrum disorders. However, we cannot, based on our study, specify whether this relationship is caused by genetic or environmental factors.     

Psychiatric effects of exposure to suicide among the friends and acquaintances of adolescent suicide victims.

The friends and acquaintances (N = 58) of 10 adolescent suicide victims were interviewed 6 months after the death of the victims, and the rates of psychiatric disorders that had onset after the death were compared with the 6-month incidence of psychopathology in 58 demographically and psychiatrically matched unexposed controls. The exposed group showed higher rates of any new onset major depressive disorder, but the rate of incident suicide attempts was the same in both groups. The median onset of incident depression among the exposed group was within the first month after exposure, and the majority of those exposed youth with incident depression were still depressed at interview 6 months after the death. Adolescent friends and acquaintances of suicide victims experience considerable psychiatric morbidity subsequent to exposure to suicide, most consistent with pathological grief.     

Follow-up and family study of anxious depression

OBJECTIVE: The failure of the concept of anxious depression to find its way into DSM-III-R led the authors to conclude that a further report on the occurrence of anxiety symptoms in depressed subjects is indicated. METHOD: The subjects were 327 consecutively evaluated inpatients and outpatients with primary unipolar depressive disorder at five university medical centers participating in the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies. The authors restricted their sample selection to patients with primary depressive disorder so that patients with other preexisting psychiatric disorders, especially anxiety disorders, would not contaminate the symptom picture, family studies, or follow-up. The examined six anxiety symptoms and derived a new anxiety summary score to show the effect of anxiety in depression on family data and 5-year outcome. RESULTS: Depressed subjects with higher ratings for anxiety took longer to recover. There was also a significant relationship between anxiety in depressed probands and the risk for primary unipolar depressive disorder, but not anxiety disorders or alcoholism, among 832 blindly interviewed first-degree relatives. CONCLUSIONS: These data confirm the usefulness of subdividing depressed patients according to anxiety symptoms: psychic and somatic symptoms of anxiety, taken together, significantly predict family illness and course. The data also emphasize the wisdom of requiring that generalized anxiety disorder not be diagnosed in the presence of a mood disorder. Clearly, symptoms of anxiety coexist with depression and need to be recognized for the effective treatment of the underlying depressive disorder.     

Familial aggregation of panic disturbances in Parkinson's disease

Panic disorder has an elevated prevalence in Parkinson's disease (PD). To explore the basis for this co-occurrence, the familial aggregation of panic disorder was examined in patients with PD. Probands and relatives of patients with PD and panic disorder (PD-PANIC; N=20, N=115) and control probands with PD and no active psychiatric illness (PD-NA; N=17, N=108) were interviewed by phone, using a structured interview to determine panic status. Lifetime prevalence of panic and "panic-like" disorders was higher in PD-PANIC than in PD-NA relatives. Panic and "panic-like" disorders are familial disorders in PD.     

Hazard, heredity and depression. A family study

The relationship between proband characteristics and familial aggregation of depression was assessed in an interview study of 83 families ascertained via probands who had a recent onset of depression. Contrary to expectations and to previous reports in the literature there were no differences between the frequencies of depression in the first degree relatives of probands who had or had not experienced adversity prior to the onset of their illness. Depression was actually slightly more common among the first degree relatives of probands who had experienced a threatening life event compared with the relatives of those who had not. Early onset of depression (before 32 yr) and a neurotic pattern of symptoms in probands were associated with significantly higher rates of current illness in relatives. However, both these differences disappeared when lifetime prevalence or morbid risk to age 65 were considered. Indeed the morbid risk of severe depression in the relatives of endogenously depressed probands was nearly twice that in the relatives of neurotic probands.