Family History Method Research Articles

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurence of tic disorders and OCS might indicate heterogeneity of TS.

The validity of the family history method for identifying Alzheimer disease.

To examine the validity of the family history method for identifying Alzheimer disease (AD) by comparing family history and neuropathological diagnoses. Seventy-seven former residents of the Jewish Home and Hospital for the Aged, New York, NY, with neuropathological evaluations on record were blindly assessed for the presence of dementia and, if present, the type of dementia through family informants by telephone interviews. The Alzheimer's Disease Risk Questionnaire was used to collect demographic information and screen for possible dementia. If dementia was suspected, the Dementia Questionnaire was administered to assess the course and type of dementia, i.e., primary progressive dementia (PPD, likely AD), multiple infarct dementia, mixed dementia (i.e., PPD and multiple infarct dementia), and other dementias based on the modified Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria. Sixty (77.9%) of 77 elderly subjects were classified as having dementia and 17 (22.1%) were without dementia by family history evaluation. Of the 60 elderly subjects with dementia, 57 (95%) were found at autopsy to have had neuropathological changes related to dementia. The sensitivity of the family history diagnosis for dementia with related neuropathological change was 0.84 (57 of 68) and the specificity was 0.67 (6 of 9). Using family history information to differentiate the type of dementia, the sensitivity for definite or probable AD (with or without another condition) was 0.69 (36 of 51) and the specificity was 0.73 (19 of 26). The majority (9 of 15) of patients testing false negative for PPD had a history of stroke associated with onset of memory changes, excluding a diagnosis of PPD. Identifying dementia, in general, and AD, in particular, has an acceptable sensitivity and specificity. As is true for direct clinical diagnosis, the major issue associated with misclassifying AD in a family history assessment is the masking effects of a coexisting non-AD dementia or dementia-related disorders, such as stroke. Including mixed cases, ie, PPD and multiple infarct dementia in estimates of the familial risk for AD can reduce the extent of underestimation of PPD.

Validity of the family history method for identifying schizophrenia-related disorders

We examined the family history method's validity for identifying schizophrenia related disorders (SRD) by comparing family history and family study derived diagnoses. First degree relatives ( n=284) of 48 psychiatrically disordered probands, predominantly with schizophrenia, were diagnosed using the Family History RDC (FH-RDC) which include three psychotic schizophrenia related disorders ( P-SRD): schizophrenia, chronic SAD and chronic unspecified functional psychosis (CUFP). Supplementary criteria for schizophrenia related personality disorders (SRP), derived to identify schizotypal and paranoid personality disorders (PD), were also assessed. About two thirds of these relatives ( n=196; 69.0%) were independently diagnosed by RDC and DSM-III-R on both axis I and axis II in a family study. The specificity was 1.0 (178/178) and the sensitivity of the family history derived diagnosis for P-SRD was 0.72 (13/18). Sensitivity for P-SRD was improved, however, by inclusion of SRP which captured three of the five false negative relatives. The sensitivity of SRP for schizotypal or paranoid PD was 0.39 (15/38) and the specificity was 0.92 (127/138). The FH-RDC have moderately good sensitivity and excellent specificity for the psychotic schizophrenia related disorders. While family history criteria for SRP are not a good proxy for schizotypal or paranoid PD, they can enhance the family history method's sensitivity for SRD. © 1997 Elsevier Science Ireland Ltd.

Psychiatric disorders in the relatives of depressed probands I. Comparison of prepubertal, adolescent and early adult onset cases

Research with adults suggests that early onset of depression is associated with increased rates of depression among relatives. This paper presents results of a family study that tested the hypothesis that prepubertal depression was associated with a greater familial loading of depression than the postpubertal form, which in turn had a greater familial loading than adult onset depression. Probands were from a child to adult longitudinal study. Psychiatric disorders among relatives were assessed with family interview and family history methods ‘blind’ to all findings regarding the proband. Contrary to expectation, familial rates of depression did not differ significantly between the groups. However, manic disorders tended to be more common among the relatives of postpubertal depressed cases than among the relatives of adult onset cases. Moreover, relatives of prepubertal depressed subjects had higher rates of criminality and family discord than postpubertal subjects. Prepubertal onset depressive disorders appear to be relatively distinct from postpubertal forms.

Family history of cognitive disabilities in first-degree relatives of autistic and mentally retarded children.

We compared with a family history method the rate of cognitive disabilities (CD) in 156 first-degree relatives of 49 autistic (AU) probands to that found in 55 first-degree relatives of 18 mentally retarded (MR) probands. Broadly defined CD were found in, respectively, 17 and 16% of the relatives of the AU and MR probands. However, the characteristics of the probands associated with a family history of CD are different in AU and MR: Female and low IQ AU probands have more first-degree relatives with CD. Our findings suggest that a positive family history of CD is not specific to autism when compared to mental retardation. The observation that female and low IQ probands have higher family history of CD may suggest heterogeneity within autistic children and provides leads for future family studies.

Family history of depression in clinic and community samples

Because most published family studies of depression ascertained subjects from treatment settings, the reported familial aggregation of depression could be an artifact if a family history of depression increased the likelihood of seeking treatment. To investigate this possibility, we compared the family history of depression in three groups of probands aged 18–44: 54 women randomly selected from the community with depression in the prior year, 41 women who entered a clinical trial for depression and 37 women randomly selected from the community who had not been depressed in the prior year. The presence of depression in the parents and siblings of the probands was assessed by the family history method and quantified via family history scores which took the age, gender and number of relatives into account. Depressed probands ascertained from clinical sources had markedly higher family history scores of depression than other two groups ( P < 0.00005 in each instance). In the absence of direct interviews with relatives, we cannot exclude the impact of differential reporting. A family history of depression might be associated with an increased probability of treatment or the differential reporting of family history. It is thus possible that the familial aggregation of depression observed in probands from treatment settings is an artifact.

Major depression, minor depression, and double depression: are they distinct clinical entities?

The clinical concept of "double depression," i.e., the superimposition of a major depressive disorder in a patient with dysthymic disorder, implies that there are at least some differences between dysthymia, major depression, and double depression. However, the relationship between these two syndromes remains unclear. The present study uses genetic methodology to explore any possible relationship between minor depression, double depression, and major depression. From 1988-1990, all consecutive unrelated inpatients and outpatients (index cases) presenting to a university-based mood disorders service had detailed family histories taken, using modification of the "family history method." Diagnoses for index cases and their first-degree relatives were made according to Research Diagnostic Criteria. For all index cases with a diagnosis of minor or intermittent depression, and minor/intermittent depression plus either single or recurrent depression ("double depression"), morbidity risks for mood disorders were calculated for first-degree relatives (parents, siblings, and children) using the maximum likelihood approach. Results showed no significant differences in morbidity risk calculations to first-degree relatives of index cases with minor/intermittent depression, major depression, or double depression. The data from this genetic perspective suggest that single depression, recurrent depression, minor depression, and double depression are indistinguishable.

Reliability and reporting biases for perceived parental history of alcohol-related problems: agreement between twins and differences between discordant pairs.

Previous research suggests that family history of alcoholism assessments may be biased by characteristics of the informant. In this report, the reliability and potential biases in offspring reports of paternal and maternal alcohol-related problems were examined in a large community sample of adult twins. Subjects were volunteer participants in the Australian NH&MRC twin registry. Agreement between twin pairs on reports of paternal and maternal alcohol problems was assessed in 2,657 twin pairs (1,444 female-female pairs, 626 male-male pairs, and 587 female-male pairs). In addition, to detect systematic reporting biases, like-sex twin pairs whose paternal alcohol problems reports disagreed (n = 164) were contrasted on measures of personality, state anxiety and depression, parental rearing, alcoholism, and alcohol use. Twin agreement for parental alcohol-related problems was good, with overall kappas of .66 for paternal and .58 for maternal alcohol problems. When discordant twin pairs were compared, we found that women who reported that their father had alcohol problems were significantly lower on EPQ-R Social Conformity than their twin sister who denied paternal alcohol problems: and there was a trend for men who reported that their father had alcohol problems to be higher in negative perceived parenting from father than their twin brother who denied paternal alcohol problems. Twins discordant for reporting paternal alcohol problems did not, however, differ on the major dimensions of personality, state anxiety and depression, alcoholism, or current alcohol use. The results of this study bolster our confidence in using the family history method to examine characteristics of offspring of alcoholics versus offspring of nonalcoholics on self-reported measures of personality and psychopathology, but suggest that some caution should be exercised when using this method to examine differences in offspring-reported perceptions of parental rearing practices.

Validity of the family history method in relatives of gerontopsychiatric patients

It was the aim of the present study to evaluate the validity of the family history method in relatives of a sample of elderly subjects. A total of 201 relatives of patients and 89 relatives of control subjects were interviewed directly using the Composite International Diagnostic Interview and the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias of other Etiology. At least one relevant other could provide family history information on a respective subject. Family history information for psychiatric disorders including dementia (DSM-III-R) was neither accurate, nor sensitive (10 to 40%), but highly specific (95%). The sensitivity of the family history for dementia and depression increased in relation to the severity of the disorder. Relatives of patients were better informants than relatives of controls (at least for the presence of any psychiatric disorder). The use of several informants only slightly improved the sensitivity of the family history, without reducing the specificity to a significant extent. The combination of different sources of information may serve to reduce information biases. The evaluation of possible biases in future family studies is required to draw adequate conclusions from differences in familial loads.

Dopamine D 3 receptor Gly 9/Ser 9 polymorphism and schizophrenia: no increased frequency of homozygosity in German familial cases

Disturbances in the dopaminergic transmission have been implicated in the etiology of schizophrenia. Recently, an association of schizophrenia with increased homozygosity of a Gly 9/Ser 9 polymorphism in the dopamine D 3 receptor gene (DRD3) has been reported (Crocq et al., 1992; Mant et al., 1994). This finding reflected a departure from the Hardy-Weinberg equilibrium in the genotype distribution observed in schizophrenic patients. The effect was found to be at its strongest in patients with a high familial loading. In the present study, we tried to replicate this finding in a sample of 146 German patients with a DSM-III-R diagnosis of schizophrenia. All patients had a positive family history of major psychiatric disorder including 70 patients with a family history of schizophrenia. Given our sample size, we have a power of 99.8% to detect a deviation from the Hardy-Weinberg equilibrium of the reported magnitude. However, we found no evidence of an excess of homozygosity in our schizophrenic patients. This seems to indicate that homozygosity for the Gly 9/Ser 9 polymorphism at the DRD3 locus is unlikely to confer susceptibility to schizophrenia in the German population. This held true whether the psychiatric diagnoses in the affected relatives of the patient samples was established by the family history or family interview method.

Accuracies and inaccuracies of the family history method: a multivariate approach

This paper reports on 1459 first-degree relatives of probands with schizophrenia or affective illness and matched community controls. We sought (i) to validate psychiatric diagnoses obtained by family history (FH) against those obtained by a best estimate (BE) procedure based on personal interview and (ii) to explore the factors influencing the accuracy of the FH report. We found relatively poor agreement between the FH and BE diagnoses, and the disagreements were influenced by numerous factors, including gender, psychiatric status of the informant or proband's diagnosis. When validated against a BE diagnosis, the overall accuracy of the FH method is relatively poor, and is furthermore subject to several biases. Therefore, substituting the FH method for BE diagnosis may be an important source of error in the investigation of familial/genetic factors in psychiatric disorders.

Familial vulnerability factors to post-traumatic stress disorder in male military veterans.

The question has been frequently raised about whether there are emotional disorders that predispose to post-traumatic stress disorder (PTSD). We do know that those with PTSD do have many comorbid disorders, but due to the difficulty in performing prospective studies it is hard to tell what is cause and what is effect. This study bypassed the problem caused by comorbidity by examining family history of four proband groups: PTSD, mixed anxiety disorders, coexisting anxiety and depressive disorders, and screened normal controls. Two questions were examined. First, whether family history predicted who experienced combat situations and second, whether the proband groups could be distinguished by family history. Logistic regression identified two variables that predicted the experience of combat: major depression (odds ratio 2.17) and the DSM-III dramatic personality disorder cluster (odds ratio 1.36). Although there was considerable overlap, family history variables distinguished PTSD from other proband groups. Overall, the pattern of psychopathology in the families of the PTSD probands most closely resembled that in the families of the coexisting anxiety and depressive disorders probands. We conclude that family history methods may be an addition to possible variables that predict who will be exposed to combat and also that family history variables may be able to distinguish a PTSD population from some other types of emotional disorders.

Validity of a diagnosis of lifetime major depression obtained by personal interview versus family history

Diagnoses obtained by family history agree only modestly with those obtained through personal interview. If personal interview diagnoses are the "gold standard," these findings suggest that family history diagnoses have low validity. Here the authors take another perspective--to evaluate family history versus personal interview diagnoses of lifetime major depression by three independent validators. In a large sample of female-female twin pairs and their parents (903 families) ascertained from a population-based twin register, all subjects were personally interviewed by using a modified Structured Clinical Interview for DMS-III-R. Family history diagnoses based on the Family History Research Diagnostic Criteria were obtained by questioning each participant about his or her relatives. By means of multiple regression, the powers of the personal interview and family history methods were compared to predict 1) future episodes of major depression in the twins, 2) neuroticism, and 3) familial aggregation of major depression. Agreement between diagnoses obtained by personal interview and family history was modest. After the presence or absence of a personal interview diagnosis of major depression was controlled for, a family history diagnosis of major depression significantly predicted future episodes of major depression, neuroticism (in five of six analyses), and familial aggregation of major depression (in four of six analyses). Although agreeing relatively poorly, diagnoses of lifetime major depression obtained by personal interview and family history both contained useful information about future episodes, personality, and familial liability to illness. A multimethod approach to assessment of psychiatric illness may maximize the validity of psychiatric diagnoses.

Parents and collateral relatives of children with pervasive developmental disorders: a family history study.

The objective of this study was to see whether, using the family history method, the risk for pervasive developmental disorder (PDD), cognitive impairments, and other psychiatric symptoms is greater in the parents and collateral relatives of probands with PDD compared to a control group. A semistructured family history interview was carried out with the parents of 52 probands with PDD and 33 parents of controls. Rates of cognitive impairments and psychiatric problems were not found more frequently in parents or relatives of PDD probands compared to relatives of controls, but four cases of PDD were reported among the extended families of the PDD probands. The relatives with PDD were related to the probands through the maternal line, possibly suggesting some form of maternal influence on inheritance or reduced penetrance in females with the PDD genotype.

Psychiatric Characteristics of Children with Selective Mutism: A Pilot Study

To ascertain characteristics of children with selective mutism. Subjects with selective mutism were evaluated by means of parent and teacher rating scales and structured diagnostic interviews. Thirty children were evaluated. Mutism severity varied markedly in different environmental settings. Ninety-seven percent of the subjects were diagnosed with social phobia or avoidant disorder of childhood or adolescence or both and 30% with simple phobia. No other psychiatric disorders were common. Parent and teacher rating scales showed high levels of anxiety symptoms, especially social anxiety, and low levels of all other psychiatric symptoms. Anxiety and social anxiety severity correlated with mutism severity. First-degree family history of social phobia and of selective mutism, obtained by family history method, was present in 70% and 37% of families, respectively. There was no evidence of a causal relationship between psychologically or physically traumatic experiences and development of selective mutism. Selective mutism may be a symptom of social anxiety, rather than a distinct diagnostic syndrome. Further study of the characteristics of children with selective mutism and their families is warranted.

A Family Study of Manic-Depressive (Bipolar I) Disease

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. 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. 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. 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.

Validity of psychiatric diagnoses based on the family history method

Validity of psychiatric diagnoses based on the family history method

Risk of Alzheimer's Disease in First-Degree Relatives-Reply

In reply The reliance on informants for information on the relatives of an index subject is an inherent limitation of the family history method. However, in contrast to the weak sensitivity observed by Huen and Maier, a recent study of the validity of this method suggests that, despite this limitation, highly accurate information can be obtained. 1 Although the Dementia Questionnaire 2 was used to finally diagnose PPD in relatives, Huen and Maier's use of the Family History Questionnaire 3 as a screening tool may have contributed to the poor sensitivity observed because that instrument was not primarily designed to screen for dementia. Our approach has been to apply the Dementia Questionnaire when there was even a slight indication of memory or other cognitive problems as elicited by the Alzheimer's Disease Risk Questionnaire. 4 Furthermore, as noted in our article, 5 for investigations of late-onset diseases such as Alzheimer's disease (AD), there is

Direct comparison of the family history method and the family study method using a large stuttering pedigree

The family history method (inquiry only) was directly compared to the gold standard of the family study method (family members interviewed directly) in a large pedigree segregating a stuttering phenotype. Fifty-three individuals from one branch of a large family were asked whether they had a family history of stuttering. Additional data were collected concerning the recognition of stuttering in family members based on proximity of affected family members, affection status of the informant, gender of the informant, and the number of stutterers in the immediate family. Sensitivity was reduced for both sexes and for affected and non-affected cohorts. Affected family members had consistently higher sensitivities than non-affected family members. Gender differences were also found. Non-affected individuals' recognition of their family history was influenced by the proximity of affected family members. When the question of family history was limited to first-degree relatives, specificity was found to be high, whereas sensitivity decreased. This study confirms previous findings that the sensitivity of the family history method is reduced compared to the gold standard of the family study (Andreason et al., 1986; Thompson et al., 1982; Mendlewicz et al., 1975; Orvaschel et al., 1982). This study also replicates recent findings that affected family members are more accurate informants than non-affected family members (Kendler et al., 1991). In addition, when informants are asked to focus on first-degree relatives only (vs. the family as a whole) the sensitivity actually decreases, suggesting that familiarity may play some role in the informants failure to identify affected family members.

Biases in the Diagnosis of Alcoholism by the Family History Method

The authors explored the factors influencing the agreement of diagnoses of alcoholism obtained by a best-estimate (BE) procedure versus those obtained by family history (FH) only, based on data from the Roscommon Family Study. The participants were first-degree relatives of either schizophrenic subjects, subjects with affective disorders, or matched community controls. The FH information was obtained from first-degree relatives of the participants, whereas the BE diagnoses included personal interview and medical records as well as FH information. Two types of error were distinguished: false-negative FHs, who were diagnosed with alcoholism by BE but not by FH; and false-positive FHs, who were diagnosed with alcoholism by FH but not by BE. The risk of false-negative FHs was increased by young age of the subject and male gender of the informant, and decreased by a history of previous hospitalization of the subject. Conversely, the risk for false-positive FHs was increased by older age of the subject, male gender of the subject, female gender of the informant, and informant's diagnosis of alcoholism. Comorbid diagnosis of nonaffective psychosis increased the risk of both types of error. It is concluded that when validated against a BE diagnosis, the FH diagnosis of alcoholism is subject to several biases and that the FH method is not a satisfactory substitute for BE diagnoses.