Sex concordance for schizophrenia in families

The relationship between bipolar disorder and alcoholism: a controlled family study.

SYNOPSISBipolar disorder and alcoholism are familial disorders. The familial–genetic relationship between both is controversial and has received insufficient study. This study explores whether bipolar disorder and alcoholism share familial risk factors, and whether the co-occurrence of lifetime diagnosis of bipolar disorder and alcoholism is familial. We report on first-degree relatives of 146 consecutively admitted patients with either bipolar disorder or/and alcoholism; relatives of the patients (in total 728 relatives directly interviewed) were compared with first-degree relatives of 109 general population probands (320 relatives directly interviewed). Overlap between the familial compon…

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

Objective This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. Method The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered throug…

Alcoholism and panic disorder: co-occurrence and co-transmission in families

The co-occurrence of alcoholism and anxiety disorders in epidemiological and clinical samples is well established. Self-medication of anxiety disorder probands with the anxiolytic substance alcohol might be one reason for this association. Common susceptibility factors of both disorders might be alternative explanations. Controlled family studies recruiting probands with panic disorder and alcoholism are powerful tools to answer this question. A family study of this kind, however, is not available. The present study investigated 113 families of probands with either panic disorder or alcoholism or both (but without affective or psychotic disorders) and 80 families of healthy controls in orde…

The impact of gender and age at onset on the familial aggregation of schizophrenia.

Some recent family studies have shown that the familial risk for schizophrenia is higher in female than in male schizophrenics. It is debated whether the risks for the other disorders, such as schizotypal personality disorder or affective disorders in families of schizophrenics are similarly influenced by the proband's gender. Also, the reason for the effect of proband's gender on the recurrence risk for schizophrenia has not been clarified. This family study (159 probands, 589 first degree relatives) confirms that schizophrenia, but also schizophrenia spectrum disorders were more frequent in families of female compared with male schizophrenics. Neither age at onset in probands nor the inte…

A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q

Bipolar affective disorder (BPAD), also known as manic depressive illness, is a severe psychiatric disorder characterized by episodes of mania and depression. It has a lifetime prevalence of approximately 1% in all human populations. In order to identify chromosomal regions containing genes that play a role in determining susceptibility to this psychiatric condition, we have conducted a complete genome screen with 382 markers (average marker spacing of 9.3 cM) in a sample of 75 BPAD families which were recruited through an explicit ascertainment scheme. Pedigrees were of German, Israeli and Italian origin, respectively. Parametric and non-parametric linkage analysis was performed. The highe…

Personality traits as indicators of vulnerability to schizophrenia

The risk of minor depression in families of probands with major depression: sex differences and familiality.

Currently it is not clear whether minor forms of unipolar depression not matching the criteria of “major depression” should be considered as a separate diagnostic category. A controlled family study examined the familial aggregation of minor depression among probands with unipolar major depression. In the families of these probands the relative risk for minor depression was elevated by a similar magnitude to the risk for major depression. Threrefore, the diagnostic category “minor depression” would not increase diagnostic sensitivity at the expense of diagnostic specificity as far as familiality is the criterion. In agreement with recent epidemiological studies, minor depression did not rev…

Persönlichkeitsfaktoren als Risiko- und Krankheitsindikatoren der unipolaren Depression

Pramorbiden Personlichkeitszugen wird in vielen Modellvorstellungen zur Atiologie affektiver Storungen eine zentrale Rolle zugewiesen. Die klassischen Bezugspunkte sind die psychoanalytische Theorie (Abraham 1925) und die Konstitutionstypologie (Kretschmer 1921); diese Ansatze sind in den vergangenen Jahrzehnten in vielfaltiger Weise fortentwickelt worden (vgl. die Ubersichtsarbeiten von Akiskal et al. 1983; von Zerssen 1982; Tolle 1987). Bestimmten Personlichkeitszugen bzw. Personlichkeitstypen wird dabei entweder die Rolle eines a) Risikofaktors, der uber ein theoriespezifisches pathogenetisches Bindeglied mit dem Auftreten der Erkrankung in Verbindung gebracht wird, oder b) die Rolle ein…

Morbid Risks in Relatives of Affective, Schizoaffective, and Schizophrenic Patients — Results of a Family Study

Affective disorders have been the major focus of recent family studies; the results of many family studies agree as regards the increased morbid risks for family members of patients with affective disorders and the distinction between unipolar and bipolar affective disorders. However, in spite of the large number of family studies that have been done there are still some unsettled problems, such as the association of delusional unipolar depression and bipolar depression (Weissman et al. 1986), the relationship of anxiety disorders and depressive disorders in families (Leckman et al. 1983), and the modeling of the association between depression and alcoholism in families (Merikangas et al. 1…

Personality patterns in subjects at risk for affective disorders.

The main conclusions of this study on the familial links between personality patterns and affective disorders are: (1) The personality features with the greatest degree of symptomatic overlap with unipolar depression were more common among the first-degree relatives of probands with this diagnosis: thus dysthymic temperament and neuroticism are enhanced in this group of relatives compared to controls. Likewise personality features with a high degree of symptomatic overlap with bipolar affective disorder were more common among the first-degree relatives of probands with this diagnosis. Thus levels of dysthymic and cyclothymic temperament were elevated in this group of relatives compared to c…

A controlled family study in panic disorder.

Abstract There are only a few family studies in panic disorder. Although there is some evidence that panic disorder is familial, the exact figures of the familial risk for this disorder are at variance across different studies; the impact of comorbidity and of the gender of relatives is also unclear. Family studies in panic disorder controlling for the comorbidity in probands are therefore indicated. This study presents the morbid risks in families of 40 “pure” panic disorder probands (DSM-III-R) without a history of psychotic disorders, major depression or alcoholism compared with families of 80 controls recruited in the general population. The relative frequency of panic disorder (DSM-III…

Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.

Previously reported linkage of bipolar affective disorder to DNA markers on chromosome 18 was reexamined in a large sample of German bipolar families. Twenty-three short tandem repeat markers were investigated in 57 families containing 103 individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII), nine with schizoaffective disorder of the bipolar type (SA/BP), and 38 individuals with recurrent unipolar depression (UPR). Evidence for linkage was tested with parametric and non-parametric methods under two definitions of the affected phenotype. Analysis of all 57 families revealed no robust evidence for linkage. Following previous reports we performed separate analyses afte…

Mutationsanalyse des 5-HT1A-Rezeptor-Gens bei schizophrenen und affektiven Psychosen

Storungen im Serotoninstoffwechsel werden bei einer Vielzahl neuropsychiatrischer Erkrankungen (z. B. Angststorung, Depression, Schizophrenie, Alkoholismus, Migrane, Aggressives Verhalten, Suizidalitat, Tourette-Syndrom) beobachtet. Die Serotonin (5-Hydroxytryptamin, 5-HT) Rezeptoren konnen in mindestens drei Hauptgruppen unterteilt werden und zwar in 5-HTr, 5-HT2- und 5-HT3-Rezeptoren. Beim Menschen konnten bislang funf 5-HTrRezeptorsubtypen kloniert werden: der 5-HT1A, 5-HT1Dα, 5-HT1Dβ, 5-HT1E und der 5-HT1F Rezeptor (Ubersicht bei Shih et al. 1995). Der 5-HT1A ist der pharmakologisch am besten charakterisierte 5-HT1-Subtyp.

Vulnerabilität für Schizophrenie: Entwicklung einer Modellvorstellung anhand von Familienstudien

Vulnerabilitatsmodelle fur schizophrene und affektive Storungen gehen davon aus, das sowohl klinische Storungen als auch subklinische Varianten und Normabweichungen durch dieselben disponierenden Faktoren evoziert werden. Die Starke der Vulnerabilitat (Disposition) zu einer Storung bildet sich auf einer Dimension ab, die durch die additive Wirkung verschiedener Ursachenbedingungen determiniert wird; die verschiedenen Auspragungsstufen auf dieser Dimension drucken sich in unterschiedlichen, aber qualitativ ahnlichen Verhaltensmustern aus und zwar so, das mit steigender Vulnerabilitatsstarke auch die Devianz dieser Verhaltensformen zunimmt. Die maximale Auspragungsstufe dieser Vulnerabilitats…

A possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25--q26.

In an attempt to identify susceptibility loci for bipolar affective disorder, we are currently conducting a systematic genome screen with highly polymorphic microsatellite markers at an average marker spacing of 10 cM in a series of 75 families, comprising 66 families from Germany, eight families from Israel, and one family from Italy. The families were ascertained through index cases with bipolar affective disorder. The distribution of diagnoses is as follows: 126 individuals with bipolar I disorder, 40 with bipolar II disorder, 14 with schizoaffective disorder of the bipolar type, 40 individuals with recurrent unipolar depression, 51 with a minor psychiatric diagnosis, and two individuals…

Personality traits in subjects at risk for unipolar major depression: A family study perspective

Particular patterns of personality (e.g., introversion, neuroticism, obsessionality) have been found to be associated with unipolar depression by a large number of investigators; recent prospective studies have stressed neuroticism as a premorbid risk factor for depression. This study examines whether similar patterns of personality are found in relatives of affective disorder patients and of controls. First-degree relatives of normal controls and of subjects with primary unipolar depression were studied using the Munich Personality Test. Relatives in remission from an episode of unipolar depression had clearly higher levels of neuroticism and rigidity and lower levels of extraversion than …

Gegenwärtiger Stand der Kopplungsuntersuchungen bei Schizophrenie

Fur schizophrene Erkrankungen besteht ein deutlich erhohtes genetisches Risiko, belegt durch Familien-, Zwillings- und Adoptionsstudien [1]. Die Konkordanzrate bei eineiigen Zwillingen betragt etwa 50%, ein im Vergleich zu zweieiigen Zwillingen etwa 3fach erhohtes Erkrankungsrisiko [1]. Ein einfacher Mendelscher Erbgang mit einem einzigen verantwortlichen Genort ist jedoch nicht nachweisbar. Schizophrene Erkrankungen gehoren wie zum Beispiel auch Diabetes, Bluthochdruck, Krebserkrankungen, zu den komplexen genetischen Erkrankungen mit polygener, bzw. multifaktorieller Vererbung.

Untersuchungen zur Kopplung zwischen Schizophrenie und der pseudoautosomalen Region

Fur die Suche nach Genorten fur genetisch determinierte Erkrankungen mit Hilfe von Kopplungsanalysen werden zwei Strategien angewandt: 1. das systematische Absuchen des Genoms auf Kopplung von Genort mit Marker mit Hilfe von DNA-Markern (RFLP, Short Tandem Repeats) in regelmasigen Abstanden, 2. die Verwendung von DNA-Markern zur Kopplungsanalyse in Kandidatengenregionen, fur die ein Zusammenhang mit der Erkrankung angenommen wird, bei psychiatrischen Erkrankungen, z. B. Genorte fur Enzyme, Rezeptoren, Transporter fur Neurotransmitter.

Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36–43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a non-parametric method, sib pair analysis, a P value of 0.068 correspon…

Personality disorders among the relatives of schizophrenia patients.

In light of current linkage studies in schizophrenia, research on the "schizophrenia spectrum" deserves increased attention for an exact determination of the affected phenotype: Those disorders that have a much higher prevalence among biological relatives of schizophrenia patients are supposed to share common etiological factors with "core" schizophrenia. However, there is controversy over which of the DSM-III-R personality disorders should be included in the spectrum. In a controlled family study of inpatients with a DSM-III-R diagnosis of schizophrenia (n = 101), schizophreniform and schizoaffective disorders (n = 69), and unipolar major depression (n = 160), familial rates of personality…

Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study.

Background: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. Methods: Index probands met Research Diagnostic Criteria for SCZ (n=146), schizoaffective (SA [n=115]), bipolar (BP [n=80]), or unipolar major depressive (UP [n=184])disorder. Comparison probands met Research Diagnostic Criteria fo…

The reliability of the SADS-LA in a family study setting

The joint-rater and test-retest reliability study of two translated versions of the SADS-LA (Schedule for Affective Disorders and Schizophrenia--Lifetime version--modified for the study of anxiety disorders), one in French and the other in German, have been tested in family study settings, in a sample of patients and first-degree relatives. The test-retest reliability study demonstrated that identification of major affective disorders and schizophrenia was performed with sufficient reliability; however, diagnoses of subtypes of major disorders (e.g. bipolar II disorder) and identification of minor disorders was less reliable. The implications of these findings in phenotype identification du…

Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene.

In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains a …

The familial relationship between panic disorder and unipolar depression

Abstract This controlled family study explores (1) whether panic disorder and unipolar depression share familial factors, and (2) whether the co-occurrence of lifetime diagnoses of panic disorder and unipolar depression in individuals defines a distinct diagnostic subtype in terms of familial aggregation. To be most informative, the familial lifetime prevalence rates for panic disorder and unipolar depression have to be determined in a set of four proband groups: 78 patients with unipolar depression and panic disorder, 121 patients with unipolar depression alone (no panic disorder), 81 patients with panic disorder alone (no unipolar depression), and 109 control probands sampled in the gener…