Sex concordance for schizophrenia in families

Untersuchte Stichproben, Durchführung und Methoden

Stichprobe 1 (Untersuchung der Reliabilitat und Validitat — mit Ausnahme der Anderungssensitivitat):

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…

The Personality Sphere in Patients with Panic Attacks

Reliability and validity of the Newcastle Scales in relation to ICD-9-classification

The assessment of endogenous depression by means of the Newcastle Scales (1965, 1971) has been validated by their correlation with biological findings in many previous studies. However, reliability and cross validation studies are lacking for these scales. We found the reliability of the Newcastle Scales to be sufficient or at least moderate in a sample of 70 inpatients with major depression. In order to cross validate both scales, the clinical classification according to ICD-9 and the assessment of the Newcastle Scales have been performed independently in a sample of 112 inpatients with Major Depressive Disorder (RDC). The rate of agreement between clinical diagnosis and classification acc…

Fragile-X carrier females: evidence for a distinct psychopathological phenotype?

The present study examined 35 mothers (29 premutation carriers) of children with fragile-X syndrome in measures of intelligence and psychiatric disorders by comparing them with two control groups: a) 30 mothers of children in the general population and b) 17 mothers of non-fra-X retarded children with autism. Premutation carriers had a higher frequency of affective disorders than mothers from the general population. Preliminary data indicate that normally intelligent premutation carriers of the fra-X genetic abnormality have a similar frequency of affective disorders (DSM-III-R criteria [APA, 1987]) than mothers of autistic children. Neither carriers of the premutation nor carriers of the f…

Brief depression among patients in general practice

Depression with substantial psychosocial impairment, but not qualifying as depressive disorder according to the standard diagnostic manuals, is frequent among primary care patients. Recurrent brief depression (RBD) is a diagnostic category intended to identify a major proportion of this group of patients. The WHO study on "Psychological Problems in Primary Health Care" was used as a vehicle to estimate the proportion of patients with this diagnosis and to evaluate the validity of this diagnosis as well as of alternative concepts of brief depression with multiple episodes. This study applies a two-stage sampling scheme; 300 patients also underwent an additional interview tailored for variant…

An interdisciplinary study towards a multiaxial classification of male sexual dysfunction

The classification of male sexual dysfunction (SD) was investigated in a multidisciplinary study involving a sample of 25 outpatients whose phenomenology, course and biologic comorbidity is described. All 25 patients were suffering from arousal disorders; 9 men complained of lack of desire and 9 of orgasm disorders. For the vast majority (19/25), the arousal disorder preceded the other sexual dysfunctions. Eleven patients suffered from a psychopathological disorder according to DSM-III or DSM-III-R (Axis I and II), with general anxiety, major depression and obsessive-compulsive personality being the most common disorders. Only 6 patients were free of any organic disorder or pathological lab…

Relation of schizophrenia and panic disorder: Evidence from a controlled family study

The intention of this controlled family study was to evaluate reasons for comorbidity of schizophrenia and panic disorder. Observed rates of psychiatric disorders in first-degree relatives of patients and of controls were compared with rates predicted by possible hypotheses explaining comorbidity. The sample consisted of 59 patients with schizophrenia (including seven with schizophreniform disorder), 54 patients with panic disorder (with or without agoraphobia), 29 comorbid patients with lifetime diagnoses of panic disorder and schizophrenia (or schizophreniform disorder, 2 patients) and 109 controls, and their 1068 first-degree relatives. Information from clinical performance, clinical and…

Evidence against linkage of schizophrenia to chromosome 5q11-q13 markers in systematically ascertained families.

Ten pedigrees systematically ascertained in Germany were tested for linkage to chromosome 5q11-q13. In order to replicate the previous report by Sherrington et al (1988), families with a bipolar family member were omitted from the lod score calculations, all diagnoses were based upon Research Diagnostic Criteria, and four different models of the affection status were calculated, including the model for which Sherrington et al calculated the highest lod scores. None of the families investigated showed a positive lod score. Using multipoint linkage analyses, we were able to exclude the region for which a positive linkage has been reported.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale

Schennach-Wolff R, Obermeier M, Seemuller F, Jager M, Messer T, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkotter J, Heuser I, Maier W, Lemke MR, Ruther E, Klingberg S, Gastpar M, Moller H-J, Riedel M. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. Objective:  To examine depressive symptoms, their course during treatment, and influence on outcome. Method:  Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to w…

Reliabilität und Validität der Hamilton-Depressionsskala und ihrer Subskalen

Die Mittelwerte und Varianzen der Globalsummenscores fur die 17-Item-Version und 21-Item-Version der HAMD (Tab. 19) liegen im Bereich der in anderen Studien angegebenen Normwerte fur depressive stationare Patienten (Baumann, 1975; Maier et al. 1984; Hedlund, 1979).

Reliabilität der diagnostischen Klassifikation

Das Ziel dieser der Untersuchung der Validitat vorgeschalteten Reliabilitatsstudie ist es, den Gebrauch strukturierter Interviews zu legitimieren. Die Hypothese ist, das jedenfalls fur Subtypen depressiver Syndrome durch ein strukturiertes Interview eine hohere Reliabilitat erzielt werden kann als durch die Verwendung von Checklisten.

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…

Assessment of frontal lobe functioning in schizophrenia and unipolar major depression.

This study has used neuropsychological tasks – Wisconsin Card Sort (WCST), Trail Making (TMT) A and B, Verbal Fluency, Digit Span – to compare acute and currently off-medication schizophrenics, patients with unipolar nonpsychotic major depression and healthy controls. Both patient groups differed significantly from healthy controls in their neuropsychological performance. Furthermore there was only little (quantitative) difference between schizophrenics and depressed patients in the frontal lobe associated tasks: WCST, TMT and Verbal Fluency. Depressed patients tended to perform worse than schizophrenics on Digit Span, a task hypothesized to involve other than frontal areas of the brain. Al…

The concept of major depression. II. Agreement between six competing operational definitions in 600 psychiatric inpatients.

Six operational definitions of the concept of major depression were submitted to empirical evaluation in 600 psychiatric inpatients. Special attention was given to the comparison of major depression in DSM-III-R and ICD-10. The data base created by a polydiagnostic interview revealed relevant classificatory differences between the six definitions under study. Sources of different diagnostic base rates were: inclusion or omission of anhedonia as an obligatory mood criterion; minimal number of syndrome criteria required for the syndrome diagnosis; different width and reference points of time criteria; exclusion rules for co-existing schizophrenic symptoms and for previous nonaffective and man…

Zusammenfassende Wertung und Konsequenzen für die Klassifikationsforschung

Die abschliesende Wertung der 3 Validierungsstudien stost auf das Problem des „multiplen Testens“. Die Klassifikation endogener Depressionen wurde nach dem polydiagnostischen Ansatz durchgefuhrt; weiterhin wurden 6 weitere Subtypisierungen depressiver Syndrome vorgenommen. Wenn aber 20 verschiedene Klassifikationssysteme parallel verwendet werden, und fur jede der 20 diagnostischen Differenzierungen bezuglich eines Kriteriums die Validitat gepruft wird, so sind 20 Signifikanztests durchzufuhren; bereits im Rahmen der zufallsbedingten Variationen ist bei mindestens einem der Klassifikationssysteme ein signifikantes Ergebnis (p=.05) bezuglich eines ausgewahlten Validierungskriteriums zu erwar…

Subtyping panic disorder by major depression and avoidance behaviour and the response to active treatment

In order to establish the clinical validity of currently used ways of subtyping panic disorder the predictive power of associated current avoidance behaviour and (secondary) major depression for the response to active treatment (alprazolam, imipramine) was tested. The analysis was based on the data from the Cross-National-Collaborative-Panic-Study. Limited support for validity evidenced by predicting drug response was found for grading panic disorder by the severity of avoidance behaviour; patients with panic attacks and agoraphobia are more responsive to imipramine (compared with alprazolam) when using the reduction of the total number of panic attacks (or of spontaneous panic attacks) as …

Influencing factors and predictors of early improvement in the acute treatment of schizophrenia and schizophrenia spectrum disorder.

Abstract Background To examine the influencing factors and predictors of early improvement in schizophrenia patients. Methods 370 patients suffering from a schizophrenia spectrum disorder were examined within a naturalistic multicenter study. Early improvement was defined as a ≥30% PANSS total score reduction within the first two treatment weeks, response as a ≥50% improvement of the PANSS total score from admission to discharge and remission according to the consensus remission criteria. Baseline and course-related variables such as positive, negative and depressive symptoms, side effects, functioning and subjective well-being were examined regarding their explanatory value for early impro…

Ziel der eigenen vorliegenden Arbeiten

Ziel dieser Untersuchung ist es, die verschiedenen Versionen der Hamilton-Depressionsskala (17-Item-Version, 21-Item-Version, die isolierten Subskalen der HAMD) und die neuen alternativen Skalen MADRS und BRMS an demselben Kollektiv depressiver Patienten vergleichend auf ihre Reliabilitat und Validitat zu prufen. Vergleichende Analysen von Schweregradskalen sind notwendig, um unter den konkurrierenden Schweregradskalen jene zu finden, die am besten als Indikator fur die Intensitat depressiver Syndrome geeignet ist. Mit Ausnahme der Arbeit von Maier und Philipp (1985a) vergleichen die in der Literatur verfugbaren Arbeiten maximal 2 Skalen; die verwendeten Reliabilitats- und Validitatskriteri…

One-year follow-up of cardiac anxiety syndromes. Outcome and predictors of course.

In a representative sample (n = 31) of patients with panic attacks and a cardiac anxiety syndrome, a prospective follow-up study after a 1-year interval was performed. At the follow-up assessment 33% of the patients were in remission, whereas the majority of patients had an unfavorable course. Avoidance behavior and female sexual status were found to be predictive for an unfavorable course. Within a matched-pair design controlled for age and sex, no difference between panic disorder with and without cardiac anxiety syndrome was observed in any psychosocial or psychopathological outcome variable. This result is an argument against the validity of the subtype cardiac anxiety syndrome.

Abschließende Diskussion zur Reliabilität und Validität der Schweregradbeurteilung

In Ubereinstimmung mit anderen Untersuchungen (Bech et al. 1976, 1981, Maier und Philipp, 1985a, Cichetti und Prusoff, 1982, Rehm und O’Hara, 1984) belegen die vorgelegten Untersuchungen Mangel in der Reliabilitat und Validitat der gangigen Versionen der Hamilton-Depressionsskala (21-Item-Version und 17-Item-Version). Insbesondere die unzureichende interne Konstruktvaliditat belegt, das der Globalsummenscore dieser Skala in unterschiedlichen Stichproben depressiver Patienten eine unterschiedliche Bedeutung haben kann; so reprasentiert der Globalsummenscore in der Stichprobe von leichteren depressiven Syndromen vorwiegend die mit der depressiven Symptomatik assoziierte korperliche Symptomati…

Response trajectories in "real-world" naturalistically treated schizophrenia patients.

Abstract Background To date, research has identified distinct antipsychotic response trajectories yet focussing on data from randomized-controlled trials (RCTs). Therefore, the heterogeneity of response in “real-world” schizophrenia patients is still unknown. Methods Antipsychotic response was evaluated in 399 patients suffering from a schizophrenia spectrum disorder within a naturalistic multicenter study of the Competence Network on Schizophrenia using latent class regression. Baseline and illness-related variables were compared between the different trajectory classes as well as currently proposed outcome definitions (early improvement, response, remission) using univariate tests. In ord…

Subtypes of panic attacks and ICD-9 classification.

No single ICD-9 category corresponds to panic disorder (DSM-III). To investigate whether patients with panic attacks can be identified by means of ICD-9, 97 patients with three panic attacks within 3 weeks were recruited from various medical centers, and were classified independently according to DSM-III and ICD-9. The ICD-9 diagnoses were scattered over a broad range of categories, and it was impossible to identify patients with panic disorder in this manner. Anxiety state, affective psychosis, and depressive neurosis were the most frequent ICD-9 diagnoses. The boundary between affective psychosis on the one hand and anxiety state and depressive neurosis on the other hand was validated by …

Untersuchungen mit dem Validierungskriterium „Langzeitverlauf“

Untersuchungsziel ist die vergleichende Validierung unterschiedlicher Subtypisierungen depressiver Syndrome am Kriterium des Langzeitverlaufs. Dabei werden fur die Validierungsprufung die beiden in der neueren Literatur gangigen Teilkriterien „Dauer der Indexepisode“ und „Dauer des episodenfreien Intervalls“ verwendet. Um die Anzahl wesentlicher Validierungskriterien moglichst gering zu halten, wird dem zuletztgenannten Teilkriterium die Prioritat gegenuber dem erstgenannten Teilkriterium gegeben. Diese Rangordnung rechtfertigt sich aus den Schwierigkeiten zur Messung der Dauer der Indexepisode (s. u.).

A SCAN-SADS comparison study of psychotic subjects and their first-degree relatives

Two diagnostic interviews, the Schedule for Affective Disorders and Schizophrenia (lifetime version) (SADS-LA) and the Schedule for the Clinical Assessment of Neuropsychiatry (SCAN) were compared for main diagnoses and for their acceptibility to psychotic subjects and their psychiatrically well relatives. Broad agreement for DSM-III, DSM-III-R and draft ICD-10 diagnoses was good, although there were areas of disagreement between the two interviews which are discussed.

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…

Treatment of chronic depression with sulpiride: evidence of efficacy in placebo-controlled single case studies

Systematic variation of treatment (alternating active drug and placebo in four treatment periods) in individual patients is proposed to collect preliminary evidence for a therapeutic effect of sulpiride in chronic depression; the ARIMA model is applied to evaluate the intervention effects of the tentatively effective treatment in single subjects. Ten single cases of chronic depression with a diagnosis of major depression or dysthymia were selected and seven of these provided evidence for beneficial effects of sulpiride with regard to treating the symptoms of depression and anxiety. However, the drug effects were intraindividually not always replicable. The results obtained with these single…

Wisconsin Card Sorting Test: an indicator of vulnerability to schizophrenia?

The Wisconsin Card Sorting Test (WCST) is a neuropsychological test, hypothesized to be an indicator of dorsolateral prefrontal cortex (DLPFC) functioning. The performance of schizophrenic patients in our sample (off medication) was worse than the performance of healthy controls in all variables of the WCST, including perseverative responses (PR) as well as non-perseverative responses (NPR). The rate of perseverative and non-perseverative responses was neither a function of the severity of the illness (measured by SANS/SAPS scales) nor the duration of the disease. Healthy siblings of schizophrenic probands revealed more perseverative responses than healthy controls, but did not show any dif…

Schizophrenia and left hemisphere dysfunctions a controlled neuropsychological study in schizophrenics and their relatives

Insight in schizophrenia–course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder

AbstractBackgroundTo analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight.MethodsInsight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients.ResultsAlmost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight …

Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

AbstractLiability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnosed AD. Genome - wide data on 14,904 individuals with AD and 37,944 controls from 28 case / control and family - based studies were meta - analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome - wide significant effects of different ADH1B variants were identified in European (rs1229984; p = …

Reliabilität und Validität der Montgomery-Asberg-Ratingskala und der Bech-Rafaelsen-Melancholieskala

Die Mittelwerte und Standardabweichungen der Globalsummenscores der MADRS und der BRMS sind mit den in der Literatur angebenen Werten vergleichbar (Tab. 29).

Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

Schennach-Wolff R, Jager M, Seemuller F, Obermeier M, Schmauss M, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkotter J, Heuser I, Maier W, Lemke MR, Ruther E, Klingberg S, Gastpar M, Moller H-J, Riedel M. Outcome of suicidal patients with schizophrenia: results from a naturalistic study. Objective:  Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. Method:  Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorder…

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…

Measuring the Efficacy of Psychotropic Drugs: Clinical Symptoms and Rating Scales

The pathophysiology of anxiety, affective and schizophrenic disorders is not known. Therefore the efficacy of psychotropic drugs cannot be tested by their effect on the pathophysiology of mental disorders. The efficacy of psychotropic drugs in the treatment of acute episodes can only be evidenced by the reduction of indicators of the severity of the target symptomatology in the controlled drug trials.

Personality traits as indicators of vulnerability to schizophrenia

The use of research assistants in polydiagnostic research.

Untersuchungen mit dem Validierungskriterium „Therapieansprechen“

Untersuchungsziel ist der Vergleich der Validitat von unterschiedlichen Verfahren zur Subklassifikation depressiver Syndrome bezuglich des Kriteriums „Ansprechen auf antidepressive Therapie mit Trizyklika“. Das Ansprechen auf antidepressive Therapie wird durch Schweregradskalen fur die depressive Symptomatik gemessen. Neben der Hamilton-Depressionsskala werden noch 2 weitere Depressionsskalen (Montgomery-Asberg-Depressions-Ratingskala, Bech-Rafaelsen-Melancholieskala) verwendet. Um die Anzahl der Indikatoren fur die Validitat bezuglich des Kriteriums „Therapieanspechen“ moglichst gering zu halten, wird der mit der Hamilton-Depressionsskala erfaste therapeutische Effekt als das vorrangige Va…

The impact of sex, age at onset and birth complications on the risk of schizophrenia in a family study sample

Attitude towards adherence in patients with schizophrenia at discharge

Abstract Background Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied. Methods Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towa…

Chronology of panic and avoidance, age of onset in panic disorder, and prediction of treatment response. A report from the Cross-National Collaborative Panic Study.

The relevance of the chronology between panic disorder and avoidance behavior and of an early, medium or late onset of panic disorder was tested. Groups from the sample of the cross-national collaborative panic study (CNCPS) were compared for differences in basic characteristics and for the ability to predict treatment response. Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment. Patients with an early onset of panic disorder suffered more often from agoraphobia. The treatment response was similar in the groups with early, medium or late onset of panic disorder. Neither …

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…

Comparative analysis of observer depression scales

Abstract The Hamilton Depression Scale (HAMD), Bech Rafaelsen Melancholia Scale (BRMS) and Montgomery Asberg Depression Rating Scale (MADRS) are analyzed according to mean discriminatory power, internal consistency, homogeneity and transferability. The analysis was done separately in different samples of patients with depressive syndromes: a) operationally defined depressive syndrome; b) Major Depressive Disorder (RDC); c) Major Depressive Disorder, endogenous type (RDC). BRMS and MADRS were superior to HAMD in all evaluated aspects. Further, the BRMS was superior to MADRS according to the criteria of homogeneity and transferability.

The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: results of a controlled family study.

The aim of the study was to differentiate bipolar II, bipolar I and recurrent unipolar depression by their familial load for affective disorders. Eighty bipolar, 108 unipolar, 80 control subjects and interviewed first-degree relatives were diagnosed according to Research Diagnostic Criteria using the Schedule for Affective Disorders and Schizophrenia – lifetime version. The morbid risks for bipolar I disorder were equivalent in relatives of bipolar I (3.6%) and bipolar II (3.5%) subjects and lower in relatives of unipolar subjects (1.0%). The morbid risks of relatives for bipolar II disorder distinguished bipolar II subjects (6.1%) from bipolar I subjects (1.8%), from unipolar depressives (…

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…

Genetic contribution to alcohol dependence: Investigation of a heterogeneous german sample of individuals with alcohol dependence, chronic alcoholic pancreatitis, and alcohol-related cirrhosis

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be …

The impact of the endogenous subtype on the familial aggregation of unipolar depression.

The endogenous/non-endogenous distinction of unipolar major depression is widely accepted, as is the family study approach to the validation of diagnostic distinctions. Rates of affective disorders were examined in 689 first-degree relatives of 184 patients with unipolar major depression and were compared with 312 first-degree relatives of 80 healthy controls. Only unipolar depression and alcoholism were more common in families of depressed probands compared with families of healthy controls. As a variety of diagnostic definitions of endogenous depression have been proposed, probands and relatives were diagnosed in a polydiagnostic manner. None of the five diagnostic definitions of endogeno…

Drug treatment of panic disorder: early response to treatment as a predictor of final outcome

One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome. To analyze potential predictors of outcome, data of a multicenter study on patients with panic disorder were used. A total of 1010 patients were randomly allocated either to alprazolam, imipramine or placebo treatment. Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group. In contrast, placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity. For tricyclic antidepressants such as imipramine an evaluation peri…

A polydiagnostic scale for dimensional classification of endogenous depression. Derivation and validation.

Several operational diagnoses (OPD) for endogenous depression have been proposed. However--though aiming at similar clinical concepts--the amount of association and agreement between different OPD is rather low. In this study the relationship between eight OPD (Research Diagnostic Criteria, DSM-III, Michigan Discrimination Index, Newcastle Scale I, Newcastle Scale II, Taylor-Abrams Criteria, Vienna Research Criteria, Hamilton Endogenomorphy Index) was assessed by applying latent trait analyses to the classificatory data of these eight OPD which were rated simultaneously in a sample of 173 depressive inpatients. According to these analyses six OPD (RDC, DSM-III, NCS-I, NCS-II, TAC and VRC) a…

DSMIIIR personality disorders of the schizophrenic spectrum as evidenced by family studies

Diagnoses as Selection Criteria in Drug Trials

Drug trials are needed to establish the efficacy and safety of psychopharmacological agents in clearly defined indications. When the goal of treatment is more complex than removal of an isolated symptom (“difficulty in falling asleep” or “pain”) the syndrome or clinical entity to be treated is most easily classified by way of a diagnostic label (like “depression,” “schizophrenia,” or “panic disorder”). Dimensional models have many advantages: they often fit the data better and provide a conceptual framework for a continuum in the behavior from normal to abnormal. However, they have never reached the popularity of typological models (Strauss 1973, 1975, 1986) which reflect more the medical t…

Challenging the understanding of significant improvement and outcome in schizophrenia - the concept of reliable and clinically significant change methods

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thre…

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…

Reliability of DSM-III Anxiety Disorders - Check-List Versus Structured Interview

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…

Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder.

Abstract Background Dysfunctions of serotonergic neurotransmission are supposed to be involved in the pathogenesis of psychiatric disorders such as major depressive disorder (MDD). The concentration of serotonin (5-hydroxytryptamine, 5-HT) in the synaptic cleft is essentially regulated by the 5-HT transporter (5-HTT). A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders. Methods Genotyping of the 5-HTTLPR is time-consuming and technically challenging. Recently, a two-SNP haplotype was identified that tags the 5-HTTLPR at r 2 =0.775. This allows extraction of 5-HTTLPR genotype information from…

The concept of major depression. III. Concurrent validity of six competing operational definitions for the clinical ICD-9 diagnosis.

The comparative validity of six operational diagnoses of major depression was evaluated in 600 psychiatric inpatients using the independently assessed clinical ICD-9 diagnoses as a yardstick. Agreement with, and positive predictive value for the ICD-9 categories of pure (endogenous and psychogenic) depression served as validation criteria; sensitivity of major depression diagnoses for detecting ICD-9 bipolar depressions was additionally used for examining the adequacy of width, time and exclusion criteria of the competing operational definitions. Three essential results were found. First, the "old" diagnostic definitions of RDC and FDC are superior to all newer definitions because they defi…

Zusammenfassung der Untersuchungen zur Klassifikation und Schweregradbeurteilung depressiver Syndrome

Die Entwicklung und die Bewertung (Validierung) von Diagnosesystemen und Schweregradbeurteilungen depressiver Syndrome sind mit dem Problem der unbekannten Atiologie und Pathophysiologie depressiver Syndrome konfrontiert. Daher mussen Beurteilungssysteme zur Diagnosestellung und Schweregradmessung weitgehend auf psychopathologische Merkmale gestutzt werden; die Validierung dieser Beurteilungssysteme mus sich auf indirekte Indikatoren (Validierungskriterien) der Atiologie und der Intensitat des zugrunde liegenden Krankheitsprozesses stutzen. Klassifikationssysteme und Schweregradskalen fur depressive Syndrome beziehen sich gleichermasen auf psychopathologische Querschnittssymptome (von Vorve…

Subclinical thought disorder in first-degree relatives of schizophrenic patients. Results from a matched-pairs study with the Thought Disorder Index

To assess the frequency and quality of formal thought disorder in schizophrenic patients and their first-degree relatives, a consecutive series of 36 unmedicated patients, 20 siblings of these patients and 37 normal control subjects were examined with Holzman's Thought Disorder Index (TDI). As a proof of the internal validity of this tool, the patients demonstrated significantly more thought disorder than the controls as measured by the TDI total score and various subscores, which proved the internal validity of this tool in a German-speaking sample. In addition, in a pairwise comparison with controls who were individually matched by age and sex the patients' siblings had a significantly hi…

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.

Genome-wide Association Study of Alcohol Dependence

Context Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder. Objective To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset. Design The GWAS tested 524 396 single-nucleotide polymorphisms (SNPs). All SNPs with P −4 were subjected to the follow-up study. In addition, nominally significant SNPs from genes t…

Depression in the community: a comparison of treated and non-treated cases in two non-referred samples.

Family studies in non-patient samples may help to clarify whether or not treatment-seeking behaviour is substantially determined by clinical features of depression. Life-time risks of depression were investigated by structured clinical interviews (SADS-LA) in both a high-risk sample of depressed patients' first-degree relatives and an unscreened control sample of the general population: 34.6% of the high-risk sample versus 23.1% of controls were cases of depression, with a female preponderance in both groups. The rates of treated depression were 17.0% versus 8.5%. Female sex, greater age, higher severity of episodes, manic or hypomanic episodes recurrent course, and introverted and anancast…

The Hamilton Depression Scale and Its Alternatives: A Comparison of Their Reliability and Validity

The efficacy of medical treatments is evidenced by a demonstrated reduction in the severity of the disorder being treated relative to a control condition. At the beginning of the era of psychopharmacology, in the late 1950s, neither a well-defined concept nor a well-defined measurement of the severity of depression, schizophrenia, or anxiety disorders were available. Consequently, it was difficult to compare groups of treated patients on the basis of treatment-specific rates of recovery. Hamilton was one of the first to recognize this lack and to create methods for standardizing the measurement of the effects of drugs across both patients and treatments. His idea was that a standardized mea…

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…

Bipolar II disorders in six first-degree relatives

As proposed by Dunner et al (1976), the distinction of bipolar !! disorder from other effective disorders has been included in Research Diagnostic Criteria (RDC) (Spitzer et al 1978) but not in DSM-IiI-R or ICD 10 (APA 1987, WHO 1991). Family studies indicate that bipolar 1I disorder might represent a distinct diagnostic entity with a common genetic background (Gershon et al 1982; Dunner 1983; Endicott et al 1985; Andreasen et al 1987). Familial aggregation, diagnostic stability, and course of illness represent external validators for nosologic classifications (Kendler 1990). Therefore, pedigrees with multiple cases of diagnostically stable bipolar Ii disorder without cases of bipolar 1 dis…

Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.

We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independe…

XRCC5 as a Risk Gene for Alcohol Dependence : Evidence from a Genome-Wide Gene-Set-Based Analysis and Follow-up Studies in Drosophila and Humans

Genetic factors play as large a role as environmental factors in the etiology of alcohol dependence. Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of alcohol dependence, many true findings may be missed due to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals. Gene-set based analysis of GWAS data from 1333 cases and 2168 controls identified 19 significantly associated gene-sets of which five could be replicated in an independent sample. Clustered in these ge…

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…

Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo

Summary Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment. The safety, side effects and patients' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study. Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation, fatigue/weakness, memory problems, ataxia and slurred speech…

Inhabiting plant roots, nematodes, and truffles—polyphilus, a new helotialean genus with two globally distributed species

Fungal root endophytes, including the common group of dark septate endophytes (DSEs), represent different taxonomic groups and potentially diverse life strategies. In this study, we investigated two unidentified helotialean lineages found previously in a study of DSE fungi of semiarid grasslands, from several other sites, and collected recently from a pezizalean truffle ascoma and eggs of the cereal cyst nematode Heterodera filipjevi. The taxonomic positions and phylogenetic relationships of 21 isolates with different hosts and geographic origins were studied in detail. Four loci, namely, nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]), partial 28S nuc rDNA (28S), partial 18S nu…

One-year follow-up of panic disorder. Outcome and prognostic factors.

A 1-year follow-up study was carried out in 77 patients with panic attacks (panic disorder). Of these patients 43% were remitted; avoidance behaviour and chronic anxiety were more persistent than panic attacks within the 1-year period. The main predictor for features of anxiety in the follow-up was avoidance behaviour. The most prominent prognostic factor for features of depression was the history of previous depressive episodes. Female patients had a poorer outcome than male patients.

Cognitive functioning and anhedonia in subjects at risk for schizophrenia

This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did …

Normabweichungen der Frontalhirnfunktion bei gesunden Angehörigen schizophrener Patienten

Verschiedene Untersuchungsmethoden (MRT, rCBF) weisen auf eine Assoziation zwischen frontalen Hirnarealen und der Schizophrenie hin. In diesem Zusammenhang ist jedoch ungeklart, ob die postulierte Beteiligung des Frontalhirns eine Folge oder ein pramorbides Charakteristikum der Schizophrenie darstellt.

The relevance of recurrent brief depression in primary care. A report from the WHO project on Psychological Problems in General Health Care conducted in 14 countries.

This report from the WHO project on Psychological Problems in General Health Care examines the relevance in primary care of the concept of recurrent brief depression (RBD) proposed by Jules Angst. RBD refers to brief, severe depressive episodes that recur frequently, i.e. nearly once a month over, a 1-year period, according to Angst. Using a structured interview (CIDI), RBD was assessed in patients not meeting the criteria for depressive episodes lasting at least 2 weeks, as defined in the ICD-10 (DE). A substantial proportion of primary care seekers were identified as presenting RBD without other depressive disorders, 3.7% with a formal RBD diagnosis and 2.7% with frequent but not monthly …

Risperidone in the Treatment of Disorders with a combined Psychotic and Depressive Syndrome - A Functional Approach

In vitro receptor-binding profiles and in vivo pharmacological studies have shown risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor antagonist. While anti-D2 activity may relate to the antipsychotic potency of neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity has been suggested. In an open pilot-study, ten patients with schizodepressive disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and UKU for the assessment of side-effects. Generally, the psychotic syndr…

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 …

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study

AbstractObjectiveTo examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.MethodsTwo hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.ResultsReceiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total sco…

Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females

Abstract The present French–German investigation of fragile-X syndrome (fra-X) was undertaken to disentangle genetic from environmental effects on cognitive performance as assessed with the following measures: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wisconsin Card Sorting Test, Trail-Making Test, Tower of Hanai, Verbal Fluency Test, Stroop Test, short-term and consolidation memory, and the d2 task. Groups with different genotypes ( n =11 mothers with a full mutation in the FMR-1 gene of fra-X children; n =65 mothers with a premutation in the FMR-1 gene of fra-X children; n =18 siblings of these mothers with normal CGG repeats) and with different psychosocial stressors from fra-X…

Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single-marker tests and a polygenic score-based analysis to assess the …

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.

Consistencies and discrepancies in self- and observer-rated anxiety scales. A comparison between the self- and observer-rated Marks-Sheehan scales.

The Marks-Sheehan anxiety scales are the only scales where self-ratings and observer ratings are perfectly matched by the number, the content and the scaling of the items. Therefore these scales are an excellent tool to investigate the compatibility and to study different structures in self- and observer ratings. This was done by using the data material on the Marks-Sheehan scales of the Cross National Collaborative Panic Study. In this study 1168 outpatients who met the DSM-III criteria for panic disorder were randomly allocated either to alprazolam, imipramine or placebo treatment. Our results show that the Marks-Sheehan scales are highly comparable to other established rating scales. Bot…

Positive/negative symptomatology and experimental measures of attention in schizophrenic patients.

In a search for an external validation of the negative syndrome construct and the attentional impairment item on Andreasen's scale, 49 unmedicated schizophrenic patients were administered the Span of Apprehension Test and a Continuous Performance Test with two levels of difficulty. This schizophrenic sample performed significantly more poorly on the attentional tests than a comparable group of 27 healthy control subjects. Depending on the difficulty of the test we found a number of significant correlations between the SANS composite score and the pertaining attentional impairment item on the one hand and experimental indices of attentional functioning on the other hand, which might corrobor…

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

Polymorphism in the peroxisome proliferator-activated receptor ? gene influences the risk for Alzheimer?s disease

The peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a member of the steroid hormone super family of ligand-inducible transcription factors, involved in glucose and lipid metabolism. We screened for polymorphisms in the PPAR-alpha gene and detected two known polymorphisms located in exon 5 and intron 7. These polymorphisms were investigated for their possible association with Alzheimer's disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism. The PPAR-alpha C --G polymorphism in exon 5 (L162V) was associated with AD, in that the V-allele was more frequent in AD patients than in healthy subjects. Further data analysis revealed that carriers of an …

Reaction time paradigms in subjects at risk for schizophrenia.

Abstract Deviant response patterns in experimental reaction time paradigms in schizophrenic probands are well documented. Although simple reaction times are strongly influenced by the current psychopathological status of the proband (e.g. florid psychotic patients versus remitted patients) these influences are less clear for measures obtained from more complex reaction time paradigms. These include the crossover paradigm (reaction time to stimuli presented after constant preparatory intervals in comparison to reaction time to stimuli presented after irregular preparatory intervals) and the modality shift paradigm (reaction time to a stimulus (light or tone) when the modality of the stimulus…

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.

Untersuchungen zum Validierungsparameter „familiäre Belastung“

Untersuchungsziel ist die vergleichende Validierung unterschiedlicher Subtypisierungen depressiver Syndrome am Kriterium der familiaren Belastung (bezogen auf Angehorige 1. Grades) mit „major depression“, wiederkehrender „major depression“, beliebigen Formen affektiver Erkrankungen und Alkoholismus. In der Literatur werden 2 dieser 4 Kriterien eine besondere Prioritat zugewiesen: der familiaren Belastung mit „major depression“ und der familiaren Belastung mit Alkoholismus (Weissman et al., 1986, Winokur, 1986). Die beiden anderen Angehorigendiagnosen, die sich auf affektive Erkrankungen beziehen (wiederkehrende „major depression“, jegliche Form affektiver Erkrankungen) werden verwendet, um …

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

AbstractEating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], …

Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders.

Abstract Background: To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group. Method: PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score > 61 (Global Assessment of Functioning Scale), SOFAS score > 61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore > 40 (Medical Outcomes Study—Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid cl…

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…

Recurrent brief depression in general practice. Clinical features, comorbidity with other disorders, and need for treatment.

This study tested the clinical validity of the new diagnostic entity "recurrent brief depression" (RBD) in 300 general practice patients who participated in the WHO study on "Psychological Problems in Primary Care." Patients with current RBD reported of episodes major depression more often than did a comparison group of nondepressed general practice patients: however, the majority of RBD patients had not received a diagnostic of any well-established affective disorder during the last 12 months. RBD patients (without MDE) did not suffer more frequently from dysthymia, from nonaffective psychiatric disorders, or from somatic disorders. However, RBD was associated with a higher percentage of p…

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6…

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

AbstractBackgroundPurpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.MethodThe subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logisti…

Intra- and Interhemispheric Electroencephalogram Coherence in Siblings Discordant for Schizophrenia and Healthy Volunteers

Former studies had pointed to an increased electroencephalogram (EEG) coherence in schizophrenics, but it remained unsolved whether this deviation represents the premorbid state or is only a consequence of the current or previous schizophrenic episodes. To clarify this question, we tested the hypothesis that subjects at elevated risk also reveal higher coherences compared to healthy controls. For that, intra- and interhemispheric EEG coherences were investigated in untreated schizophrenics, their healthy siblings, and healthy controls. Differences were only found regarding the intrahemispheric coherences. Both in schizophrenics and, even though to a lesser degree, in their siblings signific…

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in …

Avoidance behaviour: A predictor of the efficacy of pharmacotherapy in panic disorder?

The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study (n = 1134 patients); in this double blind randomized trial alprazolam, imipramine and placebo were compared during an 8-week treatment period. Patients with extensive avoidance behaviour (agoraphobia) had the most profit from the active drugs. Counter expectancy these specific drug effects were most pronounced in avoidance behaviour. Active drugs (in particular imipramine) were especially more effective than placebo if the patients presented with associated avoidance behaviour. The results suggest that agoraphobia defines more a particul…

Neuropsychological deviations in healthy relatives of schizophrenics

A German Validation Study of the Inventory to Diagnose Depression

The Inventory to Diagnose Depression (IDD), a self-rating scale designed to identify major depressive episodes (MDE) according to DSM-III, was validated in a sample of 83 inpatients. Depending whether the time criterion of MDE was included or omitted, 63 or 77 patients obtained a syndrome diagnosis of MDE established by means of a structured clinical interview (Polydiagnostic Interview) which served as yardstick. Sensitivity (84.1% with time criterion, 89.6% without time criterion), specificity (60%, 50%), predictive value (67.8%, 64.2%) and kappa (0.43, 0.29) were calculated and found to necessitate improvement for a reasonable application of the IDD in epidemiological and clinical setting…

Internal and external validity of the WHO Well-Being Scale in the elderly general population

The objectives of this study were (i) to evaluate the validity of the WHO Well-Being Scale in elderly subjects and (ii) to assess the influence of demographic variables on subjective quality of life. A sample of 254 elderly subjects completed the 22-item WHO Well-Being Scale. The scale had an adequate internal and external validity. However, the short 10-item and 5-item versions were equally valid. Low scores indicating decreased well-being were related to the presence of a psychiatric disorder or, independently, to poor living conditions. The Well-Being Scale and their short versions would appear to be useful instruments for identifying subjects with reduced subjective quality of life.

Reliability and Validity of the Assessment of Antidepressant Effects

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…

The cardiac anxiety syndrome ? a subtype of panic attacks

Cardiac anxiety syndrome and the diagnosis of cardiac neurosis respectively are characterized by panic attacks. Panic attacks are the core syndrome of a validated anxiety disorder (panic disorder). The purpose of this study was to investigate if the cardiac anxiety syndrome represents a separate disorder or if it is only a subtype of panic attacks. In a sample of 122 patients with panic attacks, all patients with a cardiac anxiety syndrome were selected (n = 31). Furthermore, parallel to this group--matched in the variables age and sex--a second group of patients with no cardiac anxiety syndrome was selected. There were no significant differences in course; in clinical phenomenology, patien…

Neuropsychological indicators of the vulnerability to schizophrenia

Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings…

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…

Dimensional Classification as an Instrument for Biological Research in Endogenous Depression

Biological psychiatry needs highly reliable classifications capable of supplying research with homogeneous groups of patients. Operational diagnoses (OPD abbreviated) have been introduced to serve this aim. At present, research in endogenous depression can choose among more than ten different operational diagnoses, all purporting to be valid for diagnosing endogenous depression. Eight of these operational diagnoses are listed in Table 1.

Self- and observer assessment in anxiolytic drug trials: A comparison of their validity

Self-rating scales are considered to be less useful for comparing different treatments in anxiety patients than observer-rating scales. However, the empirical evidence for this assumption is not adequate. A self-rating inventory of 35 items related to anxiety was perfectly parallel with an observer-rating inventory. Both instruments were used in the Cross National Collaborative Panic Study to compare the efficacy of imipramine, alprazolam and placebo in an 8-week drug trial in a sample of 1168 outpatients. The variance of the self-rating assessments was about two times higher. Both scales were equally sensitive to change; however, the measurement of change by means of the self-rating scale …

The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R.

All operationalized diagnostic systems contain a diagnostic category, which corresponds to the concept of major depression. Yet, these corresponding definitions are not identical. Up to now, no comprehensive comparisons of the competing diagnoses have been published. We will therefore present a series of studies, describing six different operational definitions of major depression according to their content and construction and empirically comparing them in large inpatient and outpatient samples. This first paper presents a descriptive comparison of the definitions given in the Feighner Diagnostic Criteria, the Research Diagnostic Criteria, the Diagnostic and Statistical Manual of Mental Di…

Measures of the efficacy of psychotropic drugs in acute treatment: the current status of their validity

Weekly monitoring of dexamethasone suppression response in depression: its relationship to change of body weight and psychopathology

Abstract Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3–4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests…

The Panic-Associated Symptom Scale: measuring the severity of panic disorder.

The Panic-Associated Symptom Scale (PASS) is presented as a new measurement of the severity of the core symptoms of panic disorder. This first description addresses the rationale for its design and its scoring, score distributions, test-retest reliability, correlations within the PASS and with other scales, principal component structure, and response to drug therapy. Data are presented from a large study group of patients with panic disorder (n = 1168). Problems in measuring panic disorder are discussed.

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…

Prediction of Course in Major Depression. Does Psychopathology Predict Future Drug Intake or Relapse?

Shared genetic etiology between alcohol dependence and major depressive disorder

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Pharmacotherapy of panic attacks.

The influence of medication on the course of major depression: a 3-year-follow-up with polydiagnostic measures.

Demenzscreening im klinischen Alltag

Dementia-screening in clinical routine requires short, sensitive and specific tools. A number of standardized instruments are available for this purpose. The present study analysed the relationship between size of three exemplary dementia-screening tests and their diagnostic accuracy. The Mini-Mental-State-Examination (MMSE), the Structured Interview for the Diagnosis of Dementia of the Alzheimer-type, Multiinfarct Dementia and Dementias of other Aetiologies according to ICD-10 and DSM-III-R (SIDAM) and the Alzheimer's Disease Assessment Scale (ADAS) were applied to 71 patients with dementia of the Alzheimer-type and 73 non-demented controls. A ROC-analysis revealed that neither SIDAM nor A…

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an an…

Nicotine enhances antisaccade performance in schizophrenia patients and healthy controls

Abstract Nicotine has been proposed to be a cognitive enhancer, particularly in schizophrenia patients. So far, the published studies of nicotine effects on antisaccade performance in schizophrenia patients only tested participants who were deprived smokers. Thus, we aimed to test both smoking and non-smoking patients as well as healthy controls in order to extend previous findings. Moreover, we employed a paradigm using standard and delayed trials. We hypothesized that, if nicotine is a genuine cognitive enhancer, its administration would improve antisaccade performance both in smoking and non-smoking participants. A total of 22 patients with schizophrenia (12 smokers and 10 non-smokers) a…

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder – When, Who, and How?

Abstract The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective d…

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generat…

The role of obstetric complications in schizophrenia.

The importance of obstetric complications in sporadic and familial psychoses was analyzed in 43 schizophrenic and 28 chronic schizoaffective patients. Patients and first-degree relatives were diagnosed using Research Diagnostic Criteria and the best-estimate procedure. Mothers of patients were interviewed for histories of pregnancy and obstetric complications in their offspring. Patients had more often suffered perinatal complications (42%) than their siblings (29%). The risk for obstetric complications and secondary cases of psychosis was enhanced in relatives of patients with a history of obstetric complications. Siblings with obstetric complications had a low incidence of psychoses; ther…

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…

Remission in schizophrenia — What are we measuring? Comparing the consensus remission criteria to a CGI-based definition of remission and to remission in major depression

Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared.239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI ba…

Differentiation between major and minor depression

Though the concept of Major Depression was generated by clinicians using depressed inpatients as models, a polydiagnostic study in 600 psychiatric inpatients with heterogenous psychological disturbances revealed that all six competing operational definitions of Major Depression (including DSM-III-R and ICD-10) were too restrictive to serve as a general concept of depression. Another polydiagnostic study in 500 primary care outpatients showed that more than two-thirds of all non-chronic depressed cases were below the severity threshold of Major Depression: these patients are classified as Depression Not Otherwise Specified (NOS) by DSM-III-R. Loosening of the over-restrictive time criteria w…

Selection bias during recruitment of elderly subjects from the general population for psychiatric interviews

The aim of the present study was to determine and assess a possible selection bias in an epidemiologic investigation in the elderly. A stratified sample of 1305 probands aged 60-99 years was initially contacted by mail and then by telephone to obtain their consent to participate in a psychiatric interview. A liberal recruitment procedure led to interview participation of only 291 subjects. The proportion of younger, male, and married subjects participating in the study was greater than that of elderly, female, and single or widowed subjects. Subjects without a psychiatric lifetime diagnosis were more cooperative than those with a psychiatric disorder. The latter finding demonstrates the nee…

Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significan…

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: Identification of two naturally occurring receptor variants and association analysis in schizophrenia

A statistically significant association between a silent mutation (102T/C) in the serotonin-2A (5-HT2A) receptor gene and schizophrenia has recently been reported in a sample of Japanese patients and healthy controls. This finding suggests that genetic predisposition to schizophrenia may be affected by a functional 5-HT2A receptor variant that is in linkage disequilibrium with 102T/C. In the present study, we have sought to identify genetic variation in the 5-HT2A receptor gene by screening genomic DNA samples from 91 unrelated subjects comprising 45 patients with schizophrenia and 46 healthy controls by using single-strand conformation analysis. We have identified four nucleotide sequence …

Inhabiting plant roots, nematodes, and truffles—Polyphilus, a new helotialean genus with two globally distributed species

Fungal root endophytes, including the common group of dark septate endophytes (DSEs), represent different taxonomic groups and potentially diverse life strategies. In this study, we investigated two unidentified helotialean lineages found previously in a study of DSE fungi of semiarid grasslands, from several other sites, and collected recently from a pezizalean truffle ascoma and eggs of the cereal cyst nematode Heterodera filipjevi. The taxonomic positions and phylogenetic relationships of 21 isolates with different hosts and geographic origins were studied in detail. Four loci, namely, nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]), partial 28S nuc rDNA (28S), partial 18S nu…