Search PubMed⌕ Search

Biomedical subjects

Roselind Lieb

Publications and source records attributed to Roselind Lieb.

At least 19 recordsLinked to original sources

Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders.

BACKGROUND: There is considerable evidence that genetic factors play an important role in the pathophysiology of affective disorders including bipolar disorder, major depressive disorder and anxiety disorders. Long-term follow up studies as well as drug treatment studies suggest that these clinical conditions share a number of pathophysiological commonalities including genetic variables. One possible candidate region is located on chromosome 12q24.31, originated from previous linkage and association studies with bipolar disorder and unipolar depression. This region contains two candidate genes for purinergic ligand-gated ion channels, P2RX7 and P2RX4, and one gene coding for calmodulin-dependent protein kinase kinase b (CaMKKb). METHODS: In the present study, we investigated the genetic associations between 15 SNPs in the candidate genes P2RX7, P2RX4 and CaMKKb on chromosome 12q24.31 in 179 patients with anxiety disorders and syndromal panic attacks versus 462 healthy controls. RESULTS: One nominal case-control association could be detected for a SNP in the 5'UTR region of P2RX4, which did not remain significant after correction for multiple testing. We found, however, a prominent association between severity of panic- and agoraphobia symptoms and an exonic SNP (rs3817190) in the CaMKKb gene and a trend for association with an exonic SNP in P2RX7 (rs1718119) with severity scores in the panic- and agoraphobia scale. CONCLUSION: The locus 12q24.31 seems to be an important genetic region for anxiety, bipolar and unipolar disorders, suggesting a genetic overlap in the group of affective disorders. The specific contribution of the herein reported gene polymorphisms to the clinical condition is still unclear and warrants further analysis.

Adult↗

Childhood separation anxiety and the risk of subsequent psychopathology: Results from a community study.

OBJECTIVE: To examine the association between separation anxiety disorder (SAD) and mental disorders in a community sample and to evaluate whether separation anxiety is specifically related to panic disorder with and without agoraphobia. METHOD: The data come from a 4-year, prospective longitudinal study of a representative cohort of adolescents and young adults aged 14-24 years at baseline in Munich, Germany. The present analyses are based on a subsample of the younger cohort that completed baseline and two follow-up investigations (n = 1,090). DSM-IV diagnoses were made using the Munich Composite International Diagnostic Interview. Cox regressions with time-dependent covariates were used to examine whether prior SAD is associated with an increased risk for subsequent mental disorders. RESULTS: Participants meeting DSM-IV criteria for SAD were at an increased risk of developing subsequent panic disorder with agoraphobia (PDAG) (HR = 18.1, 95% CI = 5.6-58.7), specific phobia (HR = 2.7, 95% CI = 1.001-7.6), generalized anxiety disorder (HR = 9.4, 95% CI = 1.8-48.7), obsessive-compulsive disorder (HR = 10.7, 95% CI = 1.7-66.1), bipolar disorder (HR = 7.7, 95% CI = 2.8-20.8), pain disorder (HR = 3.5, 95% CI = 1.3-9.1), and alcohol dependence (HR = 4.7, 95% CI = 1.7-12.4). Increased hazard rates for PDAG (HR = 4.2, 95% CI = 1.4-12.1), bipolar disorder type II (HR = 8.1, 95% CI = 2.3-27.4), pain disorder (HR = 1.9, 95% CI = 1.01-3.5), and alcohol dependence (HR = 2.1, 95% CI = 1.1-4.) were also found for subjects fulfilling subthreshold SAD. CONCLUSIONS: Although revealing a strong association between SAD and PDAG, our results argue against a specific SAD-PDAG relationship. PDAG was neither a specific outcome nor a complete mediator variable of SAD.

Adolescent↗

Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and anxiety disorders with panic attacks.

Several lines of evidence suggest that anxiety disorders have a strong genetic component, but so far only few susceptibility genes have been identified. There is preclinical and clinical evidence for a dysregulation of the central gamma-aminobutyric acid (GABA)-ergic tone in the pathophysiology of anxiety disorders. Diazepam binding inhibitor (DBI) has been suggested to play a pivotal role in anxiety disorders through direct and indirect, i.e. via synthesis of neuroactive steroids, modulation of GABA(A) receptor function. These findings suggest that the DBI gene can be postulated as a candidate for a genetic association study in this disorder. Thus, single nucleotide polymorphisms (SNPs) of the DBI gene were investigated for putative disease associations in a German sample of anxiety disorder patients suffering from panic attacks and matched controls. We were able to detect a significant association between a non-synonymous coding variant of DBI with anxiety disorders with panic attacks. The rare allele of this polymorphism was more frequent in controls than in patients (OR=0.43; 95% CI: 0.19-0.95). In conclusion, these results suggest a central role of DBI genetic variants in the susceptibility for the development of anxiety disorders that are characterized by the occurrence of panic attacks.

Adult↗

P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder.

The P2RX7 gene is located within a region on chromosome 12q24.31 that has been identified as a susceptibility locus for affective disorders by linkage and association studies. P2RX7 is a purinergic ATP-binding calcium channel expressed in neurons as well as in microglial cells in various brain regions. We investigated 29 single nucleotide polymorphisms (SNPs) within the P2RX7 gene and adjacent genes in a sample of 1000 German Caucasian patients suffering from recurrent major depressive disorder (MDD). These were contrasted with diagnosed healthy Caucasian controls from the same population (n=1029). A non-synonymous coding SNP in the P2RX7 gene (rs2230912), previously found to be associated with bipolar disorder, was significantly associated (P=0.0019) with MDD. This polymorphism results in an amino acid exchange in the C-terminal cytosolic domain of the P2RX7 channel protein, suggesting that the observed P2RX7 polymorphism might play a causal role in the development of depression.

Adult↗

Where have they been? Service use of regular substance users with and without abuse and dependence.

OBJECTIVE: To present lifetime rates of service use for psychological and substance use related problems among regular substance users and to examine factors associated with service use. METHOD: Data come from a prospective-longitudinal, epidemiological study of a community sample of adolescents and young adults (n = 2548, age 14-24 years at baseline) in Munich, Germany. The Munich-Composite International Diagnostic Interview (M-CIDI) was used at baseline and at two follow-ups to assess substance use and service use. RESULTS: Cumulated lifetime incidence of any substance abuse or dependence was 43.7%. Of those with abuse and dependence 23% had ever used any services for psychological or substance use related problems. Illicit substance users especially those with dependence had the highest rates of lifetime service use (52.1%). Psychotherapists and counseling services were contacted most frequently among regular substance users over their lifetimes. Utlilisation rates of substance abuse services were low (2%). Comorbid anxiety disorders and distressing life events were associated with increased lifetime service use. CONCLUSIONS: Only a minority of adolescents and young adults with substance use disorders have ever sought professional help. Specialized substance abuse services play only a minor role. The core role of psychotherapists and non-substance abuse specialized services needs critical research attention. Linkages between psychotherapists and the substance use service system should be strengthened to detect and intervene at early developmental stages of abuse and dependence.

Adolescent↗

Clinical characteristics of major depressive disorder run in families--a community study of 933 mothers and their children.

The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother-offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children's sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.

Adolescent↗

Evidence that the outcome of developmental expression of psychosis is worse for adolescents growing up in an urban environment.

BACKGROUND: The urban environment may increase the risk for psychotic disorder in interaction with pre-existing risk for psychosis, but direct confirmation has been lacking. The hypothesis was examined that the outcome of subclinical expression of psychosis during adolescence, as an indicator of psychosis-proneness, would be worse for those growing up in an urban environment, in terms of having a greater probability of psychosis persistence over a 3.5-year period. METHOD: A cohort of 918 adolescents from the Early Developmental Stages of Psychopathology Study (EDSP), aged 14-17 years (mean 15.1 years), growing up in contrasting urban and non-urban environments, completed a self-report measure of psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around 1 year post-baseline (T1). They were again interviewed by trained psychologists for the presence of psychotic symptoms at the second follow-up on average 3.5 years post-baseline (T2). RESULTS: The rate of T2 psychotic symptoms was 14.2% in those exposed to neither Baseline Psychosis nor Urbanicity, 12.1% in those exposed to Urbanicity alone, 14.9% in those exposed to Baseline Psychosis alone and 29.0% in those exposed to both Baseline Psychosis and Urbanicity. The odds ratio (OR) for the combined exposure was 2.46 [95% confidence interval (CI) 1.46-4.14], significantly greater than that expected if Urbanicity and Baseline Psychosis acted independently. CONCLUSION: These findings support the suggestion that the outcome of the developmental expression of psychosis is worse in urban environments. The environment may impact on risk for psychotic disorder by causing an abnormal persistence of a developmentally common expression of psychotic experiences.

Adolescent↗

The accuracy of prevalence estimations for suicide attempts. how reliably do adolescents and young adults report their suicide attempts?

This study explores the accuracy of prevalence estimations for suicide attempts. Data came from the Early Developmental Stages of Psychopathology (EDSP) Study, a prospective community study (mean follow-up period was 42 months) of 3,021 respondents aged 14 to 24 years at the outset of the study. Suicide attempters are at least 1.6 times more likely to drop out than subjects with no suicide attempts and suicidal ideas. A total of 8% of all suicide attempters answered in the negative the depression-related gate questions of all surveys. One-third of all baseline suicide attempters did not report their suicide attempt again at the four years later assessment. In particular, 80% of all nonreporters were female, and almost 60% were aged 14-17 at baseline.

Adolescent↗

Substance use and substance use disorders in a community sample of adolescents and young adults: incidence, age effects and patterns of use.

OBJECTIVE: We present the prevalence and incidence rates of alcohol, nicotine, and illicit substance use, abuse, and dependence in a sample of German adolescents and young adults. Patterns of onset, cohort trends, and use of various substance classes are also analyzed. METHOD: A prospective longitudinal epidemiological study with a representative sample of adolescents and young adults (n = 3,021; baseline age range = 14-24 years) was conducted in Munich, Germany. Participants were assessed between 1995 and 1999 with the Munich-Composite International Diagnostic Interview. RESULTS: Cumulative lifetime incidence (up to age 28) of any substance abuse or dependence was 43.8%, and 12-month prevalence of any substance abuse or dependence was 24.4%. The lifetime incidence of nicotine dependence was most frequent (24.8%), followed by alcohol abuse (19.3%) and alcohol dependence (9.2%); 61.7% endorsed the regular use of a substance for at least one circumscribed period during their lifetime. Age-specific incidence rates and age at onset of substance use disorders differed by age cohorts. Furthermore, nicotine dependence was significantly associated with illicit substance use disorders (HR = 2.6, 95% CI 1.7-4.0). An interactive relationship between age, age at onset of nicotine dependence, and subsequent onset of illicit substance use disorders was found. CONCLUSIONS: Since the baseline investigation in 1995, high incidence rates of substance use disorders and substance use have been observed in this young German sample. Especially younger cohorts report significantly earlier ages at onset of abuse and dependence. There also seems to be a trend towards a secondary age at onset peak of nicotine dependence after the onset of illicit drug use disorders. Further investigations are needed to study these patterns in younger samples. However, results emphasize the need for a combined prevention of illicit drugs and nicotine dependence.

Adolescent↗

Impact of psychological trauma on the development of psychotic symptoms: relationship with psychosis proneness.

BACKGROUND: The reported link between psychological trauma and onset of psychosis remains controversial. AIMS: To examine associations between self-reported psychological trauma and psychotic symptoms as a function of prior evidence of vulnerability to psychosis (psychosis proneness). METHOD: At baseline, 2524 adolescents aged 14-24 years provided self-reports on psychological trauma and psychosis proneness, and at follow-up (on average 42 months later) participants were interviewed for presence of psychotic symptoms. RESULTS: Self-reported trauma was associated with psychotic symptoms, in particular at more severe levels (adjusted OR 1.89, 95% CI1.16-3.08) and following trauma associated with intense fear, helplessness or horror. The risk difference between those with and without self-reported trauma at baseline was 7% in the group with baseline psychosis proneness, but only 1.8% in those without (adjusted test for difference between these two effect sizes: chi2=4.6, P=0.032). CONCLUSIONS: Exposure to psychological trauma may increase the risk of psychotic symptoms in people vulnerable to psychosis.

Adolescent↗

Dependence symptoms in young cannabis users? A prospective epidemiological study.

AIM: To examine prospectively over a period of 4 years the profile of cannabis dependence and the risk of specific dependence criteria in a community sample of adolescents. METHODS: A representative community sample of 2446 young adults aged 14-24 years at baseline was followed up over a period of 4 years. Frequency of use measures and of criteria for DSM-IV dependence were assessed by standardized diagnostic interview measures (CIDI). To explore the nature of this association, frequency of use and concomitant use of other psychoactive substances was considered. RESULTS: 30% of the sample were cannabis users. Among all users 35% met at least one dependence criterion. Most frequently reported dependence criteria among all users were withdrawal (17%), tolerance (15%), loss of control (14%) and continued use despite a health problem (13%). Even without concomitant use of other illicit drugs, 22% of low frequency users and 81% of high frequency users met at least one dependence criterion. Symptom patterns were similar in high and low frequency users. The occurrence of a dependence syndrome or of specific dependence criteria could not be attributed to the use of other illicit drugs or to comorbid nicotine and alcohol dependence. CONCLUSIONS: Regular cannabis use in adolescence is associated with the development of a dependence syndrome. This association cannot be explained by the concomitant use of other illicit substances or by comorbid nicotine and alcohol dependence.

Adolescent↗

Calculating control variables with age at onset data to adjust for conditions prior to exposure.

BACKGROUND: When assessing the association between a factor X and a subsequent outcome Y in observational studies, the question that arises is what are the variables to adjust for to reduce bias due to confounding for causal inference on the effect of X on Y. Disregarding such factors is often a source of overestimation because these variables may affect both X and Y. On the other hand, adjustment for such variables can also be a source of underestimation because such variables may be the causal consequence of X and part of the mechanism that leads from X to Y. METHODS: In this paper, we present a simple method to compute control variables in the presence of age at onset data on both X and a set of other variables. Using these age at onset data, control variables are computed that adjust only for conditions that occur prior to X. This strategy can be used in prospective as well as in survival analysis. Our method is motivated by an argument based on the counterfactual model of a causal effect. RESULTS: The procedure is exemplified by examining of the relation between panic attack and the subsequent incidence of MDD. CONCLUSIONS: The results reveal that the adjustment for all other variables, irrespective of their temporal relation to X, can yield a false negative result (despite unconsidered confounders and other sources of bias).

Adolescent↗

Pathways into ecstasy use: the role of prior cannabis use and ecstasy availability.

AIM: To explore the role of cannabis use for the availability of ecstasy as a potential pathway to subsequent first ecstasy use. METHODS: Baseline and 4-year follow-up data from a prospective-longitudinal community study of originally 3021 adolescents and young adults aged 14-24 years at baseline were assessed using the standardized M-CIDI and DSM-IV criteria. RESULTS: Baseline cannabis users reported at follow-up more frequent access to ecstasy than cannabis non-users. Higher cannabis use frequencies were associated with increased ecstasy availability reports. Logistic regression analyses revealed that cannabis use and availability of ecstasy at baseline are predictors for incident ecstasy use during the follow-up period. Testing simultaneously the impact of prior cannabis use and ecstasy availability including potential confounders, the association with cannabis use and later ecstasy use was confirmed (OR=6.3; 95%CI=3.6-10.9). However, the association with ecstasy availability was no longer significant (OR=1.2; 95%CI=0.3-3.9). CONCLUSIONS: Results suggest that cannabis use is a powerful risk factor for subsequent first onset of ecstasy use and this relation cannot be sufficiently explained by availability of ecstasy in the observation period.

Adolescent↗

The use of weights to account for non-response and drop-out.

BACKGROUND: Empirical studies in psychiatric research and other fields often show substantially high refusal and drop-out rates. Non-participation and drop-out may introduce a bias whose magnitude depends on how strongly its determinants are related to the respective parameter of interest. METHODS: When most information is missing, the standard approach is to estimate each respondent's probability of participating and assign each respondent a weight that is inversely proportional to this probability. This paper contains a review of the major ideas and principles regarding the computation of statistical weights and the analysis of weighted data. RESULTS: A short software review for weighted data is provided and the use of statistical weights is illustrated through data from the EDSP (Early Developmental Stages of Psychopathology) Study. The results show that disregarding different sampling and response probabilities can have a major impact on estimated odds ratios. CONCLUSIONS: The benefit of using statistical weights in reducing sampling bias should be balanced against increased variances in the weighted parameter estimates.

Adolescent↗

The epidemiology of generalized anxiety disorder in Europe.

The objective of this paper is to provide a review on available data to date on the epidemiology of GAD in Europe, and to highlight areas for future research. MEDLINE searches were performed and supplemented by consultations with experts across Europe to identify non-published reports. Despite variations in the design of studies, available data suggest that (a) about 2% of the adult population in the community is affected (12-month prevalence), (b) GAD is one of the most frequent (up to 10%) of all mental disorders seen in primary care, (c) GAD is a highly impairing condition often comorbid with other mental disorders, (d) GAD patients are high utilizers of healthcare resources, and (e) despite the high prevalence of GAD in primary care, its recognition in general practice is relatively low. Marked data deficits are: lack of data from eastern European countries, lack of information about the natural course of GAD in unselected samples, the vulnerability and risk factors involved in the aetiology of GAD and lack of data about adequate and inappropriate treatments in GAD patients as well as the associated and societal costs of GAD.

Anxiety Disorders↗

Mania, hypomania, and suicidality: findings from a prospective community study.

We examined prospectively whether mania and hypomania are associated with an elevated risk for suicidality in a community sample of adolescents and young adults. Baseline and four-year follow-up data were used from the Early-Developmental-Stages-of-Psychopathology (EDSP) Study, a prospective longitudinal study of adolescents and young adults in Munich. Suicidal tendencies (ideation/attempts), mania, and hypomania were assessed using the standardized Munich-Composite-International-Diagnostic-Interview. At baseline, mania/hypomania was associated to a different degree with suicidality (Odds ratios [OR] range from 1.9 to 13.7). In the prospective analyses, the risk for subsequent incident suicidal ideation was increased in the presence of prior mania (38.0% vs. 14.1%; OR = 4.4; 95% CI = 1.4-13.5). No associations could be found between prior mania/hypo-mania and incident suicide attempts. The prospective analyses revealed a remarkable relationship between preexisting mania and increased risk for subsequent suicidal ideation.

Adolescent↗

Longitudinal course of posttraumatic stress disorder and posttraumatic stress disorder symptoms in a community sample of adolescents and young adults.

OBJECTIVE: Few studies have focused on the natural course of posttraumatic stress disorder (PTSD) and its determinants in samples of the general population. The authors examined determinants of remission and chronicity of PTSD and associations with other disorders in a prospective community sample. METHOD: The data were drawn from a prospective, longitudinal epidemiological study of adolescents and young adults (age 14-24 years) in Munich, Germany (N=2,548). The course of PTSD from baseline to follow-up 34-50 months later was studied in 125 respondents with DSM-IV PTSD or subthreshold PTSD at baseline. RESULTS: Although 52% of the PTSD cases remitted during the follow-up period, 48% showed no significant remission of PTSD symptoms. Respondents with a chronic course were more likely to experience new traumatic event(s) during follow-up (odds ratio=5.21, 95% confidence interval [CI]=1.95-13.92), to have higher rates of avoidant symptoms at baseline (odds ratio=10.16, 95% CI=1.73-59.51), and to report more help seeking (odds ratio=5.50, 95% CI=1.04-29.05), compared to respondents with remission. Rates of incident somatoform disorder (odds ratio=4.24, 95% CI=1.60-11.19) and other anxiety disorders (odds ratio=4.07, 95% CI=1.15-14.37) were also significantly associated with a chronic course. CONCLUSIONS: PTSD is often a persistent and chronic disorder. Specific symptom clusters--especially avoidant symptoms--might be associated with the course of PTSD. In addition, the occurrence of new traumatic events differentiates PTSD cases with a chronic course from those with remission.

Adolescent↗

Maternal suicidality and risk of suicidality in offspring: findings from a community study.

OBJECTIVE: This study evaluated the associations between suicidal ideation and suicide attempts in mothers and various aspects of suicidality in their offspring in a representative community sample. METHOD: Baseline and 4-year follow-up data were used from the Early Developmental Stages of Psychopathology study, a prospective, longitudinal community study of adolescents and young adults. Results are based on 933 adolescents who completed follow-up and for whom direct diagnostic information for the biological mother was available. Suicidal ideation and suicide attempts were assessed in adolescents and mothers with the Munich-Composite International Diagnostic Interview. RESULTS: Compared to offspring of mothers without suicidality, offspring of mothers reporting suicide attempts showed a remarkably higher risk for suicidal thoughts and suicide attempts and a tendency toward suicide attempts at an earlier age. Associations were comparable for male and female offspring. Transmission of maternal suicidality was roughly stable with control for maternal comorbid psychopathology. CONCLUSIONS: The offspring of mothers with suicide attempts are at a markedly increased risk for suicidality themselves and tend to manifest suicide attempts earlier than offspring of mothers without suicidality. Suicidality seems to run in families, independent of depression and other psychopathology.

Adolescent↗