Generalization of fear in post-traumatic stress disorder.

Overgeneralization (i.e., the transfer of fear to stimuli not related to an aversive event) is part of alterations in associative fear learning in mental disorders. In the present experimental study, we investigated whether this holds true for post-traumatic stress disorder (PTSD) related to childhood abuse. We expected that fear generalization under experimental conditions reflects generalization of aversive stimuli to different social domains in real life. Sixty-four women with PTSD after childhood abuse and 30 healthy participants (HC) underwent a differential fear conditioning and generalization paradigm. Online risk ratings, reaction time, and fear-potentiated startle served as dependent variables. Based on the subjectively assessed generalization of triggered intrusions across different domains of life, PTSD participants were split into two groups reporting low (low-GEN) and high (high-GEN) generalization. PTSD patients reported a higher expectation of an aversive event. During fear conditioning, they assessed the risk of danger related to a safety cue slower and showed a blunted fear-potentiated startle toward the danger cue. During generalization testing, reaction time increased in the high-GEN patients and decreased in the HC group with increasing similarity of a stimulus with the conditioned safety cue. Alterations of fear learning in PTSD suggest impaired defensive responses in case of a high threat probability. Moreover, our findings bridge the gap between the generalization of aversive cues during everyday life and laboratory-based experimental parameters: impairments in the processing of cues signaling safety generalize particularly in those patients who report a spreading of PTSD symptoms across different domains of everyday life.

Impact of stress on different components of impulsivity in borderline personality disorder.

BACKGROUND: Previous research on impulsivity in borderline personality disorder (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed during states of emotional distress and might be exaggerated by current attention deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed to investigate different components of impulsivity dependent on stress induction controlling for self-reported ADHD symptoms in BPD. METHOD. A total of 31 unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched for age, education and intelligence, completed self-reports and behavioural tasks measuring response inhibition (go/stop task) and feedback-driven decision making (Iowa Gambling Task) under resting conditions and after experimental stress induction. ADHD symptoms were included as a covariate in the analyses of behavioural impulsivity. Additionally, self-reported emotion-regulation capacities were assessed. RESULTS: BPD patients reported higher impulsive traits than HCs. During stress conditions - compared with resting conditions - self-reported impulsivity was elevated in both groups. Patients with BPD reported higher state impulsivity under both conditions and a significantly stronger stress-dependent increase in state impulsivity. On the behavioural level, BPD patients showed significantly impaired performance on the go/stop task under stress conditions, even when considering ADHD symptoms as a covariate, but not under resting conditions. No group differences on the Iowa Gambling Task were observed. Correlations between impulsivity measures and emotion-regulation capacities were observed in BPD patients. CONCLUSIONS: Findings suggest a significant impact of stress on self-perceived state impulsivity and on response disinhibition (even when considering current ADHD symptoms) in females with BPD.

A cross-sectional investigation of discontinuation of self-injury and normalizing pain perception in patients with borderline personality disorder.

OBJECTIVE: Several studies have shown reduced pain perception in patients with borderline personality disorder (BPD) and current self-injurious behavior (SIB). The aim of the present study was to test whether pain perception in patients with current SIB is different from that of patients who had stopped SIB, and whether pain perception of the latter group differs from healthy controls (HC). METHOD: We investigated 24 borderline patients and 24 HC. Thirteen patients showed current SIB (BPD-SIB) and 11 patients did not exhibit SIB anymore (BPD-non-SIB). Pain thresholds were assessed using thermal stimuli and laser radiant heat pulses. RESULTS: We found significant linear trends for all pain measures. The BPD-SIB group was less sensitive than the BPD-non-SIB group and the latter were less sensitive than HC. The pain sensitivity negatively correlated with borderline symptom severity. CONCLUSION: The results suggest an association between the termination of SIB, decline of psychopathology and normalization of pain perception in borderline patients.

Is the polarity of relapse/recurrence in bipolar-I disorder patients related to serum lithium levels? Results from an empirical study.

BACKGROUND: Preliminary evidence suggests that the polarity of relapse/recurrence (depressive vs. hypomanic/manic/mixed) in bipolar patients on lithium might be related to serum lithium levels. METHODS: Polarity of episodes in 64 bipolar-I patients on lithium monotherapy during a prospective 18-month maintenance trial was predicted from (a) intra-individual oscillations of lithium levels over time and from (b) absolute lithium levels preceding relapse/recurrence. RESULTS: On an individual basis, depressive (vs. hypomanic/manic/mixed) episodes were mostly preceded by lithium levels above the individual means (p<0.001). Relapse/recurrence occurring at lithium levels above the overall mean serum level of 0.66 mmol/l was depressive (not hypomanic/manic/mixed) in most cases (odds-ratio=3.86, p=0.032). Lithium levels before depressive episodes were numerically higher than before hypomanic/manic/mixed episodes (0.769+/-0.242 vs. 0.675+/-0.262 mmol/l, p=0.13). Cox-regression including current lithium levels as time-dependent predictor essentially confirmed these results. LIMITATIONS: As patients were not randomized to specific lithium levels, potential confounders could not be completely ruled out. Furthermore, a closer than monthly assessment of both lithium levels and psychopathology would have been desirable to better understand the interplay between lithium levels and new mood episodes. CONCLUSIONS: The results indicate that within the currently accepted therapeutic range (0.4-1.1 mmol/l), the relative risk for depressive vs. hypomanic/manic/mixed relapses/recurrences may be associated with higher lithium levels. Therefore, lithium levels at the lower range of the therapeutic spectrum may be sufficient for the optimal prevention of depressive episodes whereas higher lithium levels within this range may be needed for optimal protection against manic/mixed episodes.

Oligodipsia and dissociative experiences in borderline personality disorder.

OBJECTIVE: To test the frequency of attenuated fluid intake behavior (oligodipsia) in patients with borderline personality disorder (BPD) and to test if there is an inverse correlation between oligodipsia and the intensity of current dissociative experience in a pilot study. METHOD: Analyses were based on a sample of 15 BPD patients and 15 healthy controls. Fluid intake per diem and intensity of dissociative experience were measured by standardized self-reports daily for 7 days. RESULTS: The BPD patients ingested a significantly lower fluid volume per diem when compared with healthy controls (P < 0.001). We found a strong correlation between intensity of co-occurring dissociative experience and fluid intake or urine osmolality (r = 0.762 and 0.665), independently of sleep quality and general BPD symptom severity. CONCLUSION: The results indicate that oligodipsia may constitute a serious problem at least for a subgroup of BPD patients, and may be correlated with some of the most problematic symptoms of BPD.

What is the optimal serum lithium level in the long-term treatment of bipolar disorder--a review?

OBJECTIVES: There is substantial uncertainty about the most efficacious serum lithium level for the long-term treatment of bipolar disorder (BD). This review focuses on the available evidence taking into consideration the effects of previous lithium history, changes in lithium level and polarity of relapse or recurrence. METHODS: We conducted a MEDLINE search, using the MeSH Terms 'bipolar disorder' and 'lithium' together with 'randomized controlled trial' or 'controlled clinical trial' covering the time span from 1966 to March 2006. We only included studies reporting on the long-term treatment of mood disorders where patients with BD were examined as a separate group and were assigned to precisely specified target ranges of lithium level. RESULTS: The minimum efficacious serum lithium level in the long-term treatment of bipolar disorder was 0.4 mmol/L with optimal response achieved at serum levels between 0.6-0.75 mmol/L. Lithium levels >0.75 mmol/L may not confer additional protection against overall morbidity but may further improve control of inter-episode manic symptoms. Abrupt reduction of serum levels of more than 0.2 mmol/L was associated with increased risk of relapse. CONCLUSIONS: In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.

Dissociative symptoms are positively related to stress in borderline personality disorder.

OBJECTIVE: According to DSM-IV criteria, dissociative symptoms in borderline personality disorder (BPD) occur in response to stress. Empirical evidence is, however, lacking. METHOD: Using ambulatory monitoring, we assessed dissociative symptoms and subjective ratings of stress every 60 min for 48 h on a palmtop computer in BPD-patients (n = 51), clinical controls (CC; major depression n = 25; panic disorder n = 26), and healthy controls (HC; n = 40). Data analyses were primarily based on hierarchical linear models. RESULTS: In all groups, states of increased stress were paralleled by increased scores of dissociation, thus confirming the hypothesized association between stress and dissociation. The increase in dissociation was more pronounced in BPD-patients when compared with CC and HC. Additionally, BPD-patients reported heightened dissociative experience compared with CC and HC, even after controlling for stress. CONCLUSION: Our data suggest that BPD-patients might be prone to dissociation when experiencing stress and are characterized by a generally heightened level of dissociation.

Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results.

OBJECTIVES: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. METHODS: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. RESULTS: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. CONCLUSIONS: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.

Lack of association of the CD14/C-159T polymorphism with susceptibility and serological activity parameters of rheumatoid arthritis.

OBJECTIVE: CD14, the monocyte receptor for lipopolysaccharides (LPS), is an important mediator of inflammatory processes. As the T-159C exchange in the promotor of the CD14 gene was reported to lead to enhanced CD14 expression, this could be a new susceptibility gene for rheumatoid arthritis (RA). We investigated whether this single nucleotide polymorphism (SNP) serves as a risk factor for disease development or has any influence on serological activity parameters of RA or soluble CD14 (sCD14) levels. PATIENTS AND METHODS: A total of 130 patients with RA, diagnosed according to the revised American College of Rheumatology (ACR) criteria, and 130 healthy subjects, all Caucasians, were genotyped using polymerase chain reaction (PCR). Genotype frequencies were compared by chi2 analysis. RESULTS: Forty (31%) patients vs. 39 (30%) controls were genotyped CC; 71 (55%) vs. 67 (52%) were heterozygous, and 19 (15%) vs. 24 (19%) showed the TT genotype (p = 0.7). Accordingly, the allele frequency was equally distributed (p = 0.8). There was also no significant difference in genotype distribution between subgroups of patients categorized according to serological activity parameters and sCD14 levels. CONCLUSION: We found no association between the CD14/C-159T polymorphism and increased risk for the development of RA or serological disease activity parameters or sCD14 levels.

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine.

Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E(2) (PGE(2)), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE(2) production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

[Evaluation of risk assessment instruments for sex offenders]. / Rückfallprognosen bei Sexualstraftätern--Vergleich der prädiktiven Validität von Prognoseinstrumenten.

In order to evaluate risk assessment instruments for sex offenders in Germany, we compared the predictive validity of the Static-99, HCR-20, SVR-20, and PCL-R scales for 134 sex offenders. The mean follow-up time was 9 years (range 1-340 months), using the first entry into the National Register of Criminal Convictions as endpoint variable. For the estimate of predictive power, the area under the curve (AUC) of receiver operating characteristic (ROC) analysis was calculated. The AUC plots accurately identified violent or sexual recidivists and "false positives" at all scale levels. Comparing the predictive validity of these four instruments, the results favored Static-99. As for the limited sample size, differences between the assessment instruments were, however, not statistically significant. The ROC analysis for Static-99 showed that including treatment dropouts does not improve predictive accuracy (including dropouts: AUC 0.710; excluding dropouts: AUC 0.721). Kaplan-Meier survival analyses yielded highly a significant correlation to recidivism time point for two Static-99 and SVR-20 risk categories. Higher-risk categories were related to earlier recidivism. However, relying on the Static-99 and SVR-20 alone showed false positive results: for up to two out of three sex offenders, they predicted recidivism which did not occur.

Psychosocial and demographic factors associated with response to prophylactic lithium: a systematic review for bipolar disorders.

BACKGROUND: The aim was to systematically integrate the available evidence on psychosocial and demographic factors associated with response prediction to prophylactic lithium. METHOD: Each psychosocial or demographic variable that was related to lithium response in at least one study was examined with respect to response prediction. If several studies were located for the same variable results were integrated using a meta-analytical approach. To account for heterogeneity of primary studies aggregation of results was based on a random-effects model. RESULTS: Out of 27 psychosocial and demographic variables investigated in this review, nine variables were identified as significantly related to outcome under to prophylactic lithium: (1) high social status, (2) social support, (3) good compliance, and (4) dominance may be protective against a recurrence under lithium. In contrast, (5) stress, (6) high expressed emotions, (7) neurotic personality traits, (8) unemployment, and (9) a high number of life events were identified as possible risk factors for poor response. CONCLUSIONS: This systematic review shows a surprisingly high number of psychosocial variables to be related to lithium response. Effect sizes were, however, small to moderate. Many variables should, therefore, be considered simultaneously to predict response.

Which clinical factors predict response to prophylactic lithium? A systematic review for bipolar disorders.

OBJECTIVES: The aim of this study was to systematically integrate the available evidence on response prediction to prophylactic lithium based on clinical factors. METHODS: Each clinical variable that was related to lithium response in at least one prior study was examined with respect to response prediction. If several studies were located for the same variable, results were integrated using the meta-analytic approach as suggested by DerSimonian and Laird which was developed for substantial heterogeneity in primary studies. RESULTS: Of 42 potential clinical predictors investigated, five variables were identified as possible response predictors of prophylactic lithium: [1] An episodic pattern of mania-depression-interval, and [2] a high age of illness onset were identified as potentially protective against a recurrence under lithium. [3] A high number of previous hospitalizations, [4] an episodic pattern of depression-mania-interval, and [5] continuous cycling were identified as potential risk factors. Six further variables were found to be significantly related to lithium response, though calculation of fail-safe numbers indicates that current evidence is not sufficient to hold these variables as reliable predictors of lithium response. All effect-sizes relating clinical predictors to response were small to moderate. CONCLUSIONS: Although a few variables are quite robustly supported as response-predictors in this review, a more in-depth analysis of each potential predictor is needed. As none of the potential predictors had a very strong impact on response, prediction of lithium response should be based on a multitude of variables.

Is polarity of recurrence related to serum lithium level in patients with bipolar disorder?

BACKGROUND: Recently published data might indicate that the polarity of recurrence is related to lithium serum levels. To systematically test this hypothesis all published maintenance trials in bipolar disorders were examined with regard to this issue. METHOD: Maintenance studies were subdivided in trials with low (i. e. below 0.6 mEq/l),medium (i. e. 0.6 to 0.8 mEq/l) and high (i. e. above 0.8 mEq/l) lithium serum levels. Percentage of depressive vs. (hypo-)manic or mixed recurrences were compared for these three groups. RESULTS: The percentage of depressive recurrences in the groups with low, medium and high lithium levels differed in a clinically and statistically significant manner (12% vs. 38% vs. 64%, p < 0.0001). CONCLUSION: The results might indicate that low lithium levels are effective in preventing depression whereas higher blood levels are needed to prevent (hypo-)manic or mixed states.

Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression.

BACKGROUND: Early authors described hypomanic symptoms as mixed features in depressive episode, but this syndrome has not been sufficiently explored in previous studies. METHODS: 958 consecutive depressed patients were assessed by using a standardized method in terms of 43 psychiatric symptoms at hospitalization. RESULTS: A principal component analysis, followed by varimax rotation, extracted six interpretable factors: typical vegetative symptoms, depressive retardation/loss of feeling, hypomanic syndrome, anxiety, psychosis, and depressive mood/hopelessness. The extracted factor structure was relatively stable among several patient groups. There was no evidence that the hypomanic factor was exaggerated by antidepressant pretreatments before hospitalization. Bipolar diagnoses were associated with higher scores on depressive retardation and hypomanic symptoms, and a lower score on anxiety. LIMITATIONS: Psychiatric syndromes and their interrelationships, found in the present study, may be strongly influenced by the rating instrument used. The sample of this study was depressed inpatients. The results should not be generalized for depressed outpatients or epidemiological depressed populations. CONCLUSIONS: Hypomanic symptoms, as characterized by the flight of ideas, racing thought, increased drive, excessive social contact, irritability, and aggression are a salient syndrome in acutely ill depressed patients, lending support to the factor validity of mixed depression. The symptoms may not be related to pretreatments with antidepressants, or comorbidity of substance abuse, suggesting that they reflect various natural phenomenological manifestations of depressive episodes. Anxiety is unlikely to play a major role in the core phenomenological features of mixed depression. Hypomanic symptoms during a depressive episode were more represented in bipolar disorders, which may serve for further clarifications of latent bipolarity in unipolar depression, and prediction of switch into maniform states under biological depression treatments.

Concepts in the treatment of bipolar disorder.

OBJECTIVE: Concepts in the treatment of bipolar disorder are discussed considering clinical practice. METHOD: Results of the Multicenter Study of Long-term Treatment of Affective and Schizoaffective Psychoses (MAP) study, a controlled maintenance trial, are interpreted with respect to treatment concepts. RESULTS: The spectrum of patients diagnosed as bipolar has become more heterogeneous. It now comprises subtypes requiring differentiated treatment. The MAP study confirms that prophylactic efficacy of lithium seems to be specific to classic manic-depressive illness, whereas carbamazepine might be more efficacious in non-classic bipolar patients. With respect to clinical practice, treatment evaluation should also consider anti suicidal effects, inter-episodic morbidity and compliance. In these respects, results are in favour of lithium. Furthermore, data indicate that adherence to lithium clearly depends on illness concepts. This encourages efforts to supplement pharmacotherapy by psychoeducation and psychotherapy. CONCLUSION: With the broadening of diagnostic criteria, the treatment of bipolar disorder has become more complex. Patients need an integrated approach, including differentiated mood-stabilizing pharmacotherapy and psychotherapeutic measures.

Lithium in the long-term treatment of bipolar disorders.

Usefulness of lithium in the prophylaxis of bipolar disorders has been challenged for five major reasons. The authors review the empirical basis of these criticisms and come to the following conclusions. 1. Lithium efficacy is high and beyond reasonable doubt in classic manic-depressive illness. Bipolar patients presenting atypical features show a much poorer response rate to lithium. 2. There is no empirical evidence for a loss of lithium efficacy over time. 3. There is little evidence for discontinuation-induced refractoriness to lithium. 4. Lithium withdrawal phenomena are well established but seem to be rather specific to certain subgroups. Withdrawal phenomena seem to be common in atypical bipolar disorder but rare in fully stabilized classic manic-depressive illness. 5. Other factors limiting lithium efficacy in clinical practice (e. g., non-compliance) are not specific to lithium. In conclusion, prophylactic lithium does have major drawbacks and there is a clear need for more efficacious alternatives in non-classic bipolars. Compared to existing alternatives, lithium currently is to be considered the golden standard. This status might, however, be challenged by major alternative mood-stabilizers that are presently under clinical investigation.

The boundary between mixed and manic episodes in the ICD-10 classification.

OBJECTIVE: To investigate the boundary between ICD-10 mixed and manic episodes, which has apparently remained understudied. METHOD: In-patients with ICD-10 mixed (n=36) and manic episodes (n=145) were compared in terms of demographic, clinical, therapeutical and outcome variables. RESULTS: Of in-patients with manic episode, 26 (18%) had several depressive symptoms at admission. These patients (dysphoric manic patients) were very similar to patients with ICD-10 mixed episode in terms of current symptomatic presentations and several clinical and therapeutic variables, which were significantly different from those in patients with pure mania. CONCLUSION: The ICD-10 boundary between mixed and manic episodes is unlikely to be effective although experienced clinicians made the diagnoses. The system may have a high probability of diagnosing dysphoric manic patients as having manic episode, despite their great similarities to patients with mixed episode in terms of current psychopathological presentations as well as clinically important variables.

Inter-episodic morbidity and drop-out under carbamazepine and lithium in the maintenance treatment of bipolar disorder.

BACKGROUND: Evaluation of mood-stabilizing treatment strategies usually focuses on their efficacy in preventing recurrences. The aim of this study is to supplement evaluation by two important aspects: inter-episodic morbidity and drop-out. METHODS: Using a global outcome measure, response to prophylactic lithium and carbamazepine was evaluated in N = 171 bipolar patients (DSM-IV) participating in a randomized controlled trial with an observation period of 2 1/2 years (MAP study). RESULTS: The rates of re-hospitalization were similar for both treatments. However, the percentage of good clinical response (i.e. patients with a low score of inter-episodic morbidity and without both re-hospitalization and drop-out during the observation period) was significantly higher in patients randomized to lithium (40% v. 24%). This superiority of lithium resulted essentially from a lower drop-out rate in patients without re-hospitalization (17% v. 42%). Regarding severity of inter-episodic morbidity, no clear difference between the drugs was found. For both medications the predominant symptomatology was minor depressive (but not manic, mixed or schizoaffective) symptoms. In the lithium group, inter-episodic morbidity in patients without re-hospitalization significantly decreased during the first 10 months and remained on the lower level for the rest of the observation period. For carbamazepine, reduction of inter-episodic morbidity over time did not reach statistical significance. Inter-episodic morbidity was significantly related to drop-out and to re-hospitalization for both medications. CONCLUSION: Taking inter-episodic morbidity, drop-out and re-hospitalization into consideration, the response rate in bipolar patients (DSM-IV) was higher for prophylactic lithium than for carbamazepine. The global outcome parameter used appears to be a valuable measure of clinical response to mood stabilizing drugs.

The Stanley Foundation Bipolar Network: results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres.

The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in the SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar II disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean +/- SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration over time. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapid-cycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history.