Occurrence and determinants of parental psychosocial stress and mental health disorders in parents and their children in early childhood: rationale, objectives, and design of the population-based SKKIPPI cohort study.

PURPOSE: The postnatal period is a vulnerable time for parents and children but epidemiological and health care utilisation data for Germany on parental mental health during early childhood is scarce. This protocol describes the rationale, aim and study design of a population-based cohort study to assess the occurrence and determinants of psychosocial stress and mental health disorders, as well as the use and cost of health care and social services in early childhood. METHODS: As part of the collaborative SKKIPPI project, we will contact a random sample of 30,000 infants listed in the residents' registration offices of three German towns and we expect to include 6,000 mother-child pairs. Both parents are invited to fill out an online screening questionnaire. Mothers with indications of psychosocial stress will be interviewed to assess mental health disorders, regulatory problems of their children, as well as health care and social services utilisation, with a follow-up assessment after 6 months. RESULTS: After description of sociodemographic and health data, we will analyse occurrences, patterns, and potential determinants (maternal age, social status, household factors, migration status etc.) of psychosocial stress and mental health disorders in the mothers and their children in early childhood. CONCLUSIONS: Our study will identify potential risk and protective factors for postnatal mental health and health care utilization of psychosocially burdened families. This will help to improve prevention and treatment strategies to strengthen the parent-child relationship, to reduce persisting vulnerability of children, and to improve health care and social services. TRIAL REGISTRATION: The study has been registered in the German Clinical Trial Registry on February 8th 2019 (DRKS-ID: DRKS00016653).

Efficacy of Parent-Infant-Psychotherapy with mothers with postpartum mental disorder: study protocol of the randomized controlled trial as part of the SKKIPPI project.

BACKGROUND: After the birth of a child, many mothers and fathers experience postpartum mental disorders like depression, anxiety, obsessive-compulsive disorder, stress or other illnesses. This endangers the establishment of a secure attachment between the children and their primary caregivers. Early problems in parent-child interaction can have adverse long-term effects on the family and the child's well-being. In order to prevent a transgenerational transmission of mental disorders, it is necessary to evaluate psychotherapeutic interventions that target psychologically burdened parents of infants or toddlers. The aim of this trial is to investigate the efficacy of Parent-Infant-Psychotherapy (PIP) for mothers with postpartum mental disorder and their infants (0-12 months). METHODS/DESIGN: In this open, randomized controlled intervention trial 180 mother-infant-dyads will be included and randomly allocated to 12 sessions of PIP or care as usual. The interventions take place either in inpatient adult psychiatric departments or in outpatient settings with home visits. The primary outcome is the change in maternal sensitivity assessed by the Sensitivity subscale of the Emotional Availability Scale (EAS) through videotaped dyadic play-interactions after 6 weeks. Secondary outcomes are maternal psychopathology, stress, parental reflective functioning, infant development and attachment after 6 weeks and 12 months. In addition, maternal attachment (AAI) and reflective functioning (AAI) will be analyzed as potential moderators, and resource usage in the German health system as well as associated costs will be evaluated. DISCUSSION: There is increasing demand for well-controlled studies on psychotherapeutic interventions in the postpartum period that do not only focus on particular risk groups. This randomized controlled trial (RCT) represents one of the first studies to investigate the efficacy of PIP in inpatient psychiatric departments and outpatient care centers in Germany. The results will fill knowledge gaps on the factors contributing to symptom reduction in postpartum mental disorders and improvements in mother-child relationships and help in developing preventive and therapeutic strategies for the fragmented German health care system. TRIAL REGISTRATION: German Register for Clinical Trials, ID: DRKS00016353.

Prediction of lithium response using clinical data.

OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.

Performance anxiety in professional musicians: a systematic review on prevalence, risk factors and clinical treatment effects.

Music performance anxiety (MPA) is one of the most common disorders among professional musicians, nevertheless, little is known about the disease. With this systematic review, prevalence, risk factors and treatment procedures for MPA were assessed, and for the first time, quality assessments were carried out for all studies using standardized assessment tools. A systematic literature search was conducted via search algorithms in the databases MEDLINE, EMBASE, CINAHL, PsycArticles, PsycInfo and ERIC. Included were case reports, case-control, cohort, cross-sectional and intervention studies examining professional musicians with MPA. For quality assessment, adapted tools of the National Heart, Lung, and Blood Institute were used. A total of 43 studies were included (10 case reports, 21 intervention, 11 cross-sectional, one cohort study). Quality ratings ranged from -11 to 6 out of a maximum of 15/16 points for cross-sectional/cohort studies and -4 to 11 out of 18 points for intervention studies. The prevalence of MPA was between 16.5% and 60%. More women than men were affected and musicians older than 45-50 years reported less MPA than younger musicians. Regarding treatment cognitive behavioural therapy (CBT) and ß-blockers were most often researched with beneficial results for CBT. However, studies with adequate control groups for CBT interventions are needed to clarify its efficacy. Studies showed methodological weaknesses, especially in the selection of participants, recording of influencing factors, blinding of interventions, randomization of participants and analysis of comorbidity. Recommendations for further research are made.

[Ambulatory care of patients with somatically unexplained complaints : A comparative qualitative study]. / Die ambulante Betreuung von Patienten mit somatisch nicht erklärten Beschwerden : Eine vergleichende qualitative Studie.

BACKGROUND: The aim of this study was to compare the approach of general practitioners (GP) and outpatient specialists for psychiatry, neurology or psychosomatic medicine to patients with somatically unexplained complaints. METHODS: Qualitative interviews were conducted with general practitioners in Berlin and with outpatient specialists. Interviews were analyzed by qualitative content analysis. RESULTS: Both GPs and specialists rarely used structured diagnostic instruments. Guidelines are seen and used with reservation throughout the different specialties. Similar to the GPs, most of the specialists surveyed in this study had reservations against the necessity of a precise coding according to the International Classification of Diseases (ICD). CONCLUSION: In outpatient care the concern for the individual patient is the connecting element between different medical specialties. This results in a differential diagnostic and therapeutic approach that is not automatically in line with guidelines. The development of common concepts in ambulatory care might help to meet the demands of this complex group of patients with somatically unexplained complaints.

[Cost evaluation of a model for integrated care of seriously mentally ill patients]. / Kostenevaluation eines Modells der Integrierten Versorgung für schwer psychisch Kranke.

BACKGROUND: The model for integrated care (IC) of those seriously mentally ill patients insured with the DAK-Gesundheit health insurance and various Betriebskrankenkassen (members of the VAG Mitte) from the regions Berlin, Brandenburg, Lower Saxony and Bremen allows a complex treatment in the outpatient setting which consists of psychiatrists, general practitioners and clinicians, psychiatric nursing, sociotherapy (only in Berlin), internal medicine quality circles, orientation on treatment guidelines and conceptual consensus with the relevant care clinics. The aim of the evaluation is to illustrate the health economic effects of IC. METHODS: In the period from 2006 to 2010 insured members of the DAK-Gesundheit and other involved health insurance companies with a serious mental illness, a significant impairment of social functioning and the need to be treated to avoid or substitute an in-hospital stay were included in the integrated care. The cost perspective was that of the statutory health insurance companies. For the health economic evaluation, the utilisation of continuous IC over 18 months was compared to the last 18 months prior to the inclusion in IC. The clinical findings were gathered quarterly during the IC using CGI (Clinical Global Impressions) and GAF (Global Assessment of Functioning Scale). RESULTS: A total of 1 364 patients receiving IC in 66 doctor's practices were documented (of those, 286 had diagnoses of ICD-10 F2, 724 ICD-10 F32-F39). The median age was 48.8 years, 69% were female. 24% had their own source of income, 40% were on the pension, and the rest of the patients were receiving transfer benefits in some form. In 54% of the cases IC was used to avoid an in-hospital stay, in 46% of the cases to substitute an in-hospital stay. The degree of the CGI was 5.5 on average at the time of inclusion and the GAF score was 36.5 on average. The 226 patients with continuous documentation over 18 months were included in the health economic analysis. The number of days spent in hospital was lower during the IC period as compared to the 18 months prior to IV (11.8 vs. 28.6 days, p<0.001), the inpatient costs were lower (5 929 ± 13 837 Euro vs. 2 458 ± 6 940 Euro, p<0.001), the total was not significantly changed (7 777 ± 14 263 Euro vs. 7 321 ± 7 910 Euro, p=0.65). The substantial reduction of inpatient costs was compensated by the additional costs for medication and the costs of the complex outpatient care. Results were comparable for the 2 subgroups of schizophrenic/schizoaffective (n=66, 40.9 vs. 17.9 days, p=0.03; inpatient cost 9 009 ± 15 677 Euro vs. 3 650 ± 8 486 Euro, p=0.02; total expenditures 11 789 ± 15 975 Euro vs. 9 623 ± 9 262 Euro, p=0.33) and unipolar depressive patients (n=90, 29.8 vs. 9.8 days, p=0.006; inpatient cost 5 664 ± 14 921 Euro vs. 1 967 ± 5 276 Euro, p=0.02; total expenditures 7 146 ± 15 164 Euro vs. 6 234 ± 6 292 Euro, p=0.57). CONCLUSION: The IC was able to considerably reduce the utilisation of inpatient treatment through offering a complex range of services in the outpatient setting and allowed for a weight-shift in a low-threshold comprehensive care structure without an increase in costs from the statutory health insurance companies' perspective. For a detailed description of clinical effects further studies are required.

Leadership in health care: developing a post-merger strategy for Europe's largest university hospital.

PURPOSE: This paper's aim is to identify existing and developing new concepts of organization, management, and leadership at a large European university hospital; and to evaluate whether mixed qualitative-quantitative methods with both internal and external input can provide helpful views of the possible future of large health care providers. DESIGN/METHODOLOGY/APPROACH: Using the Delphi method in semi-structured, semi-quantitative interviews, with managers and employees as experts, the authors performed a vertical and a horizontal internal analysis. In addition, input from innovative faculties in other countries was obtained through structured power questions. These two sources were used to create three final scenarios, which evaluated using traditional strategic planning methods. FINDINGS: There is found a collaboration scenario in which faculty and hospital are separated; a split scenario which divides the organization into three independent hospitals; and a corporation scenario in which corporate activities are bundled in three separate entities. PRACTICAL IMPLICATIONS: In complex mergers of knowledge-driven organizations, the employees of the own organization (in addition to external consultants) might be tapped as a knowledge resource to successful future business models. ORIGINALITY/VALUE: The paper uses a real world consulting case to present a new set of methods for strategic planning in large health care provider organizations.

[Emigration of social medicine experts of the Berlin Charité to the USA - careers of the students of Alfred Grotjahn]. / Emigration von Sozialmedizinern der Berliner Charité in die USA - Karrieren der Schüler Alfred Grotjahns*

BACKGROUND: In 1920, the physician Alfred Grotjahn was appointed as first Chair for Social Hygiene in Germany at the University of Berlin. During reign of national socialism, the Institute for Social Hygiene was closed and from 1933 and 1945 transformed into an Institute for Racial Hygiene. During that period, many German scientists including social medicine co-workers of the Berlin Charité emigrated due to political, religious or racial prosecution. METHODS: The basis for this biographical presentation of co-workers of Grotjahn, who emigrated to the USA, is based on research conducted at German and American sources such as the Archive of Humboldt University of Berlin, Federal Archive in Koblenz, National Institutes of Health in Washington, NARA Archive in Washington, and Alan-Mason-Chesney Medical Archives in Baltimore. RESULTS: The Jewish scientists Franz Goldmann, Miron Kantorowicz, Alfred Korach and Georg Wollf, all former co-workers of Alfred Grotjahn, were forced to leave the country in the 30s and emigrated to the USA. They were active in different areas of public health and pursued relatively successful careers. DISCUSSION: The societal system and mentality of the USA have obviously profited from the professional background and experience arising from the emigration of former social medicine experts of the Charité.

Does prophylaxis-delay in bipolar disorder influence outcome? Results from a long-term study of 147 patients.

OBJECTIVE: This study investigated the impact of latency (the time between illness onset and initiation of prophylactic treatment) on the outcome of prophylaxis in bipolar disorders. METHOD: The effect of prophylaxis delay (latency) on the course of illness was assessed in 147 patients. Dependent variables were: reduction of days spent in the hospital (prior to vs. during prophylaxis), time to first recurrence, and Morbidity-Index during prophylaxis (lithium or carbamazepine). Latency and other independent variables were tested using a multivariate approach. RESULTS: Latency (9.3 years on average) had no significant effect on the subsequent response. Illness severity prior to prophylaxis, however, did predict the relative response. The course of illness during treatment could not be predicted by any one factor. CONCLUSION: The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.

Initial triple therapy of acute mania, adding lithium and valproate to neuroleptics.

In a closed inpatient unit, valproate and lithium were initially combined in the treatment of 12 severely manic patients (ICD-10 F30, F31, F25). Onset of response and the use of additional neuroleptic medication were analyzed. For 5 patients a comparision was performed between the index episode and a pre-treatment period during which lithium therapy was administered without valproate. Outcome criteria for the analysis were the latency of response and remission, as well as the dose of neuroleptic medication necessary for additional sedation. The mean severity of mania syndrome (AMDP-System) in the study patients was comparable to the mean mania score of the total manic patient population of the inpatient unit. All patients responded to the combination of valproate and lithium, and the mean total-remission time was 30 days for the whole group. Mean serum levels were 0.8 mmol/L for lithium and 73.8 mg/L for valproate. The mean remission time for the 5 readmitted patients was 22.8 days under combination treatment compared to 35.6 days in the pre-treatment episode without additional valproate (p = 0.06). It was possible to markedly reduce the use of neuroleptic medication in these patients from 18 601.6 mg CPZ equivalents to 3927.6 mg (p < 0.025). Initially combining valproate and lithium thus appears to be an effective therapeutic option for the inpatient management of severe manic syndromes.

Bone mineral density in pre-and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation.

BACKGROUND: Augmentation with TSH-suppressive L-thyroxine (T4) has been shown to improve the course of illness in otherwise refractory affective disorders. This collaborative study investigates whether T4 augmentation for a minimum of 12 months decreases bone mineral density (BMD) in 26 pre- and post-menopausal women with affective disorder. METHODS: We measured BMD at the femoral neck, Ward's triangle, trochanter and lumbar vertebrae (L1-L4) in 13 premenopausal and 13 postmenopausal women with affective disorder using dual energy X-ray absorptiometry. BMD was expressed as g/cm(2) and as a Z-score, calculated using bone density data from the international reference population standard. RESULTS: The Z-scores for the pre- and post-menopausal women were within the reference range of the age and sex matched population standard. BMD for the composite group also did not differ either from the population standard. BMD in the lumbar spine and hip did not differ significantly between the pre- and post-menopausal groups. However, there were a relatively high number of postmenopausal patients with BMDs one S.D. lower than the population standard. LIMITATIONS: This is a cross-sectional study with a relatively small sample size. CONCLUSIONS: The study demonstrates that T4 augmentation treatment does not reduce BMD to a clinically significant degree in many women with affective disorder. However, the resilience of bone structure to T4 treatment may vary with site and menopausal status. This study underscores the need for regular assessment of BMD during adjunctive thyroid treatments for affective disorder, especially in postmenopausal women.

Subjective response to and tolerability of long-term supraphysiological doses of levothyroxine in refractory mood disorders.

BACKGROUND: Although supplementation with supraphysiological doses of levothyroxine (T4) has been an effective treatment for refractory affective disorders in open studies, questions remain as to the tolerability of this treatment. This is the first study to investigate subjective patient response and tolerability to long-term treatment with adjunctive T4. METHODS: Of 24 patients with refractory affective disorders or schizoaffective disorder who were consecutively included into an open trial with supraphysiological T4, 16 were eligible for this study. Four measures were used to rate tolerability to T4 treatment. Subjective response was graded on a scale ranging from -33 (maximal negative response) to +33 (maximal positive response). Positive and negative effects were assessed on a structured questionnaire. Clinical tolerance was assessed with the clinician-rated Thyroid Symptom List and the self-rated Von Zerssen Complaint Lists. Outcome was assessed with the CGI for prophylactic ratings (CGI-BP). RESULTS: At the time of assessment, patients had been treated with supraphysiological T4 (mean dose 368 microg/d) for a mean of 54 months. The total subjective response score was +25.2. Positive subjective response and observer-rated treatment success were moderately correlated. Ratings on the Thyroid Symptom List indicated an overall favorable side effect profile. General physical and mental symptoms were only slightly higher than in the general population. LIMITATIONS: This was an open, cross-sectional study that only included responders and partial responders to T4 treatment. CONCLUSIONS: Subjective response and side-effect tolerability of long-term supraphysiological doses of T4 is favorable in patients with refractory mood and schizoaffective disorders who respond to the intervention.

Is there a loss of efficacy of lithium in patients treated for over 20 years?

Diminishing efficacy of lithium prophylaxis in initially well-responding patients during long-term treatment as well as after interruption of prophylaxis has been described repeatedly in the past. For the present analysis, 22 patients with bipolar and unipolar affective disorder continuously treated and documented in a specialized lithium outpatient clinic over at least 20 years were included. The cumulative affective morbidity of the first 10 years versus the second 10 years of prophylactic treatment was subjected to statistical and single-case (life chart method) analysis. There was no statistical evidence for diminishing efficacy of lithium prophylaxis. The increase in the Morbidity Index in single patients in a case-related individual approach could be revealed as not necessarily due to an alleged loss of efficacy of lithium, but more likely to be due to the atypical features in the psychopathology and course of illness.

Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.

Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects: relationship between 5HT content and 5HT uptake.

The dependence of platelet-5HT content on apparent kinetic parameters of 5HT uptake was analyzed in 56 healthy subjects and 47 depressed patients, who had not been taking psychotropic medication for several months. There were no significant relationships between apparent Vmax or Km and platelet-5HT content in both groups. However, the ratio of Vmax to Km, as a measure of apparent 5HT uptake efficiency, significantly correlated with the platelet-5HT concentration in healthy subjects (r=0.627 p<0.001). Female controls showed a higher correlation coefficient (r=0.723) than male controls (r=0.457). A marked deviation from the linear relationship between 5HT content and the ratio Vmax/K was observed in female depressed patients (r=0.250 n.s.). In male depressed patients the correlation coefficient (r=0.485 p<0.05) was similar to male healthy subjects, but the regression equations differed significantly in slope and intercept. Dividing controls and patients in subgroups with low, median and high net uptake rates, it was found that the frequencies of these uptake rate classes were 24.6%, 33.3%, 42.1% in controls and 38.3%, 44.7%, 17.0% in patients respectively. Patients and controls with low net uptake rate showed very similar uptake kinetics and uptake efficiencies, but the lack of a significant correlation between 5HT content and the ratio Vmax/Km differentiated patients from controls. The status of the serotonergic system, expressed as relationship between 5HT content and uptake efficiency, was very similar in patients and controls in the range of medium net uptake rate. A trend toward higher values of uptake efficiency was apparent in patients with high net uptake rate but the platelet-5HT content was similar to corresponding controls. Mean scores on the HAMD scale (total score and psychic anxiety item) were significantly higher in the low net uptake rate group of patients than in those with a high net uptake rate.

Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression.

OBJECTIVE: Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression. The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder. METHOD: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a randomized, parallel-group, double-blind, placebo-controlled trial of lithium augmentation during continuation treatment. After a 2-4-week stabilization period following remission, patients were randomly assigned to receive either lithium or placebo for a 4-month period. Antidepressant medication was continued throughout the study. RESULTS: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. Five of the seven relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. CONCLUSIONS: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.

Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.

Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Healthy outcome under olanzapine treatment in a pregnant woman.

Our report focuses on the case of a pregnant women with recurrent, paranoid schizophrenia. The patient was treated with Olanzapine from the 18th gestational week until delivery and during breast-feeding. No adverse events occurred during pregnancy, and the outcome was healthy. After delivery, the plasma level of olanzapine in the infant was one-third of the maternal plasma level, and during breast-feeding, it decreased to an undetectable limit.

Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.

BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.