Association between dopa decarboxylase gene variants and borderline personality disorder.

Despite heritability estimates of 37-69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene.

[Treatment satisfaction of patients with borderline personality disorder in inpatient schema therapy]. / Behandlungszufriedenheit von Patientinnen mit Borderline Persönlichkeitsstörung bei stationärer Schematherapie.

Patients with severe and chronic psychiatric disorders, such as Borderline Personality Disorder (BPD), are hospitalized frequently, but we often find a high ambivalence regarding treatment in this group of patients. 31 patients with severe BPD participated in an inpatient Schema Therapy (ST) treatment program and evaluated both the intensive ST treatment program and group therapy elements regarding their treatment -satisfaction. A high global treatment satisfaction with the ST treatment program was demonstrated and we found a higher treatment satisfaction in patients with than without BPD specific symptom reductions. Remarkable differences in treatment satisfaction showed when looking at the evaluation of group therapies. The results of the present study demonstrate treatment satisfaction of BPD patients in inpatient ST and give directions for the future development of these programs.

Serum concentrations of paliperidone versus risperidone and clinical effects.

PURPOSE: The major aim of this multicenter retrospective analysis was to examine the relationship between paliperidone serum concentrations and clinical effects in patients treated with this new antipsychotic drug. Intra-individual variability in trough serum concentrations was also analyzed in patients under treatment with either the paliperidone-extended release (ER) formulation or the risperidone immediate-release formulation. METHODS: Data were obtained from 217 patients of four medical centers who were being followed by therapeutic drug monitoring (TDM). Serum concentrations were associated with clinical response using Clinical Global Impressions (CGI) scores. RESULTS: The mean concentration of paliperidone was 36 +/- 25 ng/ml, and the mean dose corrected concentration (C/D) was 4.7 +/- 2.9 ng/ml/mg. Among patients receiving paliperidone as antipsychotic monotherapy and who showed at least a much improved level according to the CGI scores, the 25th-75th percentiles of paliperidone concentrations were 20-52 ng/ml; these were very similar to the recommended therapeutic range of 20-60 ng/ml for risperidone plus 9-hydroxy-risperidone (active moiety). In 13 patients treated with paliperidone ER and 17 patients treated with risperidone, all of whom had repeated drug measurements, the intra- and inter-individual variabilities of trough serum concentrations were similar for the paliperidone and risperidone active moiety, ranging between 30 and 35%. CONCLUSION: Based on these results, we conclude that risperidone and paliperidone have a similar therapeutic range and similar intra-individual variability in terms of trough serum levels. For treatment optimization, monitoring of plasma concentrations may be as useful for paliperidone as for risperidone.

Disturbed brain activation during a working memory task in drug-naive adult patients with ADHD.

Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) have shown abnormalities in several brain areas including the frontostriatal circuitry and were mostly conducted in children and adolescents. We investigated 30 never-medicated adult ADHD patients (16 males) and 30 matched healthy control individuals. Functional magnetic resonance imaging was acquired during a working memory paradigm (n-back). Group activation maps and group differences of activation were calculated using voxel-based analyses. The generic activation pattern was more extended in the control group. In ADHD patients, significantly decreased activation was found in the right inferior parietal cortex. Disturbed parietal brain function may particularly contribute to inattention and working memory impairment in ADHD patients.

The use of ziprasidone in clinical practice: analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey.

This study related clinical effects to daily doses and serum concentrations of ziprasidone by retrospective analysis of data from a therapeutic drug monitoring (TDM) survey established for patients treated with the new antipsychotic drug. In the total sample of 463 patients ziprasidone doses ranged between 20 and 320 mg/d and correlated significantly (r(2)=0.093, P<0.01) with serum concentrations. The latter were highly variable within and between individual patients (between patients median 67 ng/ml, 25-75th percentile 40-103 ng/ml). Pharmacokinetic interactions with comedication played a minor role. According to the clinical global impressions (CGI) scale most of the 348 patients who were under antipsychotic monotherapy with ziprasidone were either much or very much improved (43.3 and 17.3%, respectively). The previously proposed therapeutic range of 50-130 ng/ml ziprasidone in serum or plasma, which can in effect be used interchangeable, was confirmed. In patients who were at least much improved and defined as "responders" mean serum concentrations of ziprasidone were 80 ng/ml and 78 ng/ml in patients who did not reach this improvement score. In patients with serum levels above or below 50 ng/ml, the number of responders was 66 or 63%, respectively. The difference between the two groups was not significant (P=0.375), and improvement or side effects did not correlate significantly (P>0.05) with doses or serum levels. It is concluded that TDM of ziprasidone may be useful for treatment optimization because of highly variable serum concentrations resulting under therapeutically recommended doses of the drug.

Measurement of duloxetine in blood using high-performance liquid chromatography with spectrophotometric detection and column switching.

A method using high-performance liquid chromatography (HPLC) with column switching and ultraviolet (UV) spectroscopy was developed for the determination of duloxetine in human plasma. After centrifugation and addition of venlafaxine as internal standard, plasma samples were injected into the HPLC system and precleaned on a column (10 x 4.0 mm) filled with cyanopropyl (CN)-modified silica of 20 microm particle size, with use of 8% (vol/vol) acetonitrile in deionized water as eluent. Duloxetine was eluted and separated on a LiChrospher 100 CN (5-microm particle size; column size, 250 x 4.6 mm I.D.) using acetonitrile-water-potassium dihydrogenphosphate trihydrate buffer (pH, 6.4; 50:50 vol/vol) and detected at 218 nm. Duloxetine could be analyzed within 30 minutes. The limit of quantification was 5 ng/mL. At duloxetine concentrations up to 138 ng/mL that resulted from therapeutic doses of 30 to 120 mg per day, the interassay reproducibility of quality control samples was better than 12%. The method was found to be robust and stable. With the exception of chlorprothixene and desmethylclomipramine, other drugs that may be used as comedication were not found to exhibit retention times similar to duloxetine. In serum samples from 37 patients treated with 30 to 120 mg per day for at least 7 days, the mean steady state serum concentration of duloxetine was 40 ng/mL, the median was 37 ng/mL, and the 25th and 75th percentiles were 22 and 55 ng/mL, respectively. At 60, 90, and 120 mg/day, the mean +/- SD serum concentrations were 33+/-22.0, 43+/-22.2, and 48+/-17.0 ng/mL, respectively. There was a statistically significant correlation (P<0.05, r2=0.26) between prescribed daily doses and serum concentrations of duloxetine. In patients without or with comedication with other drugs, such as inhibitors of cytochrome P450 2D6 (eg, metoprolol or propranolol), serum concentrations of duloxetine were not significantly different. HPLC with column switching and ultraviolet detection as described here is suitable for pharmacokinetic studies and therapeutic drug monitoring of duloxetine.

Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis.

Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis and IND patients, but were largely absent in NIND patients. In the CSF, the majority of B cells had a phenotype of memory B cells and short-lived plasma blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients.

The role of the polio virus receptor and the herpesvirus entry mediator B genes for the development of MS.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). Although the cause of MS is still uncertain, it is well accepted that both genetic and environmental factors are important for the development of disease. In this study, we focused on the Polio Virus Receptor (PVR) and Herpesvirus entry mediator B (HVEB) receptor genes, which are located on chromosome 19q13, a region previously linked to MS. Both receptors are expressed in the brain and immune system and play an important role for inter-cellular adhesion and entry of neurotropic viruses to the brain. We identified four new polymorphisms in the PVR gene, which were located in the promoter region and three different exons. All exonic polymorphisms altered the amino acid sequence of the receptor. No new polymorphisms were found in the HVEB gene, but we confirmed a previously identified intronic polymorphism. We analyzed the frequency of the polymorphisms by RFLP analysis in sporadic MS patients, MS families, and healthy controls and determined the surface expression of HVEB and PVR on peripheral blood monocytes. We did not find differences in the frequency of the polymorphisms or surface expression between MS patients and controls. Overall, our findings do not support a role of HVEB and PVR genes in the development of MS.

The immune response at onset and during recovery from Borrelia burgdorferi meningoradiculitis.

BACKGROUND: Borrelia burgdorferi causes a wide range of neurologic syndromes. In Europe, acute meningoradiculitis is the most common manifestation. OBJECTIVE: To address the nature of the immune response during the course of B burgdorferi meningoradiculitis, with special respect to the early and late changes in cerebrospinal fluid (CSF). METHODS: Serial immunophenotyping was performed and cytokine measurements were obtained in the peripheral blood and CSF of 12 European patients with definite B burgdorferi meningoradiculitis. RESULTS: Early during infection and before initiation of treatment, we observed high levels of interleukin (IL) 10, IL-6, and IL-8, and large numbers of B cells and plasma cells in the CSF of most patients. At the same time, we found a mainly unspecific intrathecal antibody synthesis. During resolution of the infection, cytokine levels normalized rapidly and plasma cells disappeared from the CSF. In parallel, the percentage of B cells in the CSF increased over several months, accompanied by rising levels of intrathecally produced B burgdorferi-specific antibodies. CONCLUSIONS: Our findings demonstrate that the early phase of B burgdorferi meningoradiculitis is characterized by a well-coordinated immune response involving specific cytokine release and plasma cell recruitment, followed by a long-lasting, antigen-specific B-cell response in the central nervous system.