Wolfgang Jordan

Increased Prevalence of Diverse N -Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia: Specific Relevance of IgG NR1a Antibodies for Distinction From N -Methyl-D-Aspartate Glutamate Receptor Encephalitis

CONTEXT Evidence for symptomatic convergence of schizophrenia and N-methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders. OBJECTIVES To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis. DESIGN Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined. PARTICIPANTS Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n = 121), MD (n = 70), or BLPD (n = 38). MAIN OUTCOME MEASURES The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups. RESULTS Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R. CONCLUSIONS Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia and MD is different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.

Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brains mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.

Obstructive sleep apnea: Plasma endothelin-1 precursor but not endothelin-1 levels are elevated and decline with nasal continuous positive airway pressure.

Assessment of plasma endothelin-1 (ET-1) reveals conflicting results in cerebral and noncerebral conditions. Obstructive sleep apnea (OSA) syndrome has been used as a definite challenge for the investigation of endothelin measurements. Despite marked sleep-related breathing disturbances in untreated patients peripherally measurable ET-1 concentrations remained within the normal range and did not change after an appropriate therapy with continuous positive airway pressure (CPAP). In contrast, its precursor, big ET-1, was considerably elevated in untreated patients and dropped to normal values after long-term CPAP depending on compliance. Relatively stable big ET-1 elevations in untreated patients, during sleep and wakefulness, suggest that a general endothelial alteration beyond that explained by a direct impact of nocturnal breathing disturbances on the vascular system occurs. CPAP-therapy effectively lowered plasma big ET-1 in compliant patients and thus possibly their related risk for vascular diseases. Big ET-1 has been demonstrated to be a more appropriate marker of endothelial alteration than ET-1 because of its longer half-life. Simultaneous measurements are to be recommended.

First results on daytime submandibular electrostimulation of suprahyoidal muscles to prevent night-time hypopharyngeal collapse in obstructive sleep apnea syndrome.

Daytime submandibular electrostimulation (dSE) of suprahyoidal muscles was applied to prevent sleep-associated collapse of the tongue into the hypopharyngeal airway. By placing the stimulatory electrodes intra- and extraorally, recruitment of stimulated muscle fibers at low current densities was improved. The significant impact of electrostimulation on suprahyoidal muscle force was initially demonstrated in healthy controls as compared to placebo-treated volunteers. The morphology of suprahyoidal muscles was not affected by this treatment. A patient with obstructive sleep apnea syndrome initially presented with a respiratory disturbance index (RDI) of 13.2, an oxygen desaturation index of 23 and a minimal oxygen saturation of 75%. After two weeks of placebo treatment (TENS-stimulation), respiratory parameters remained unchanged. Two weeks of dSE treatment, however, improved the RDI to 3.9, the oxygen desaturation index from 23 to 2.8 and the minimal oxygen saturation from 75% to 88%. 3D-sonography showed considerable hypertrophy of the stimulated muscles. These results indicate that dSE may prevent episodes of apnea induced by sleep-associated hypopharyngeal collapse of the tongue.

Normal hypocretin-1 (orexin-A) levels in the cerebrospinal fluid of patients with Huntington's disease

A significant atrophy and loss of hypocretin neurons in the brains of human patients with Huntingtons disease (HD) and in R6/2 mice have been reported. We included 10 patients with HD and 12 patients with chorea-like hyperkinetic movement disorders (non-HD). All patients of the HD group and eleven patients of the non-HD group showed normal hypocretin-1 levels. Thus, hypocretin-1 may not serve as an additional diagnostic marker for HD.

Biochemical markers of cerebrovascular injury in sleep apnoea syndrome

Sleep apnoea syndrome (SAS) is a known risk factor for vascular diseases and stroke. Structural brain damage, manifesting as an overt neurological deficit or more subtly as cognitive dysfunction, is a frequent symptom in SAS. The presence of a biochemical marker of cerebral injury would be of great benefit in SAS to screen for even small brain damage and to monitor efficiacy of therapy. Therefore, in 10 patients with mild SAS (age 50.8±9.9 yrs, respiratory disturbance index (RDI) 18±3.6, lowest arterial oxygen saturation (min Sa,O2) 80.5±4.06%) and nine patients with severe SAS (age 50.3±11.5 yrs, RDI 75.4±21.7, min Sa,O2 56.56±14.58%), serum concentrations of neuron-specific enolase (NSE), S‐100β protein, and β‐trace were measured just before and after sleep using commercially available assays. Only serum levels in the normal range could be found, independent of when the blood was taken or the degree of SAS. Structural cerebral injury caused by sleep apnoea syndrome in patients without neurological symptoms or previous cerebrovascular events may be too small to produce a measurable increase in S‐100β, neuron‐specific enolase and β‐trace serum concentrations or subclinical cerebral damage may be outside the lower detection limits of the analytical methods which were used. There is a need for biochemical markers and more sensitive methods for detecting small cerebral injury in sleep apnoea syndrome.

Nocturnal urinary dopamine excretion is reduced in otherwise healthy subjects with periodic leg movements in sleep

The pathophysiology of periodic leg movements (PLMs) in sleep remains to be elucidated. Among other hypotheses an alteration of dopaminergic function has been suggested. Nocturnal urinary dopamine and 4-hydroxy-3-methoxyphenylacetic acid excretion in otherwise healthy subjects with PLMs was significantly reduced (P < 0.001 and P < 0.05, respectively) compared to subjects without PLMs. This finding, for the first time, demonstrates a correlate of a functionally relevant hypoactivity of the dopaminergic system in subjects with PLMs.

Aktuelle Versorgungs- und Finanzierungslage von Mutter-Kind-Einheiten für schwangerschaftsassoziierte psychische Störungen in Deutschland

UNLABELLED CONCERN: The current care and financial situation of mother-child units for psychic disorders associated with pregnancies in Germany should be documented in preparation for the development of the new reimbursement system for psychiatry and psychosomatics. METHOD In accordance with the last survey of 2005, a brief questionnaire was developed and a nationwide poll was conducted. RESULTS The survey revealed severe (10 fold) service deficits for severely and gravely mentally ill mothers, who require an inpatient treatment with specific professional competence. Compared with the last poll, these service deficits have increased. This is due to continued insufficient funding and unresolved financing in the new reimbursement system. With the establishment of an additional code for mother-child treatment the precondition for ensuring the funding of this important care form in the new reimbursement system was created. CONCLUSION It is to be hoped that the decision-makers of health policy will finally face up to their social responsibility and ensure adequate funding of the additional diagnostic and therapeutic expenditure of mother-child treatment. The health care providers have an obligation to implement a transparent record of services of the additional expenditure and to augment the national evaluation approaches to inpatient mother-child treatments.

Effects of cerebrovascular challenges on plasma endothelin

Plasma endothelin elevations have been associated with cerebrovascular pathology. Mechanisms of stimulation, however, are unknown. Therefore, in healthy subjects a marked physiological cerebrovascular response was experimentally provoked by hypercapnia, hypocapnia, and alternating capneic conditions. During these challenges plasma immunoreactive-endothelin-1 (ir-ET-1) concentrations were determined using a radioimmunassay. Physiological effects were continuously recorded for pCO(2), cerebral blood flow velocity, pulse frequency, and arterial blood pressure. No alterations in plasma ET-1 levels were found upon any of the cerebrovascular stimuli. We conclude that massive cerebrovascular challenges in healthy individuals do not lead to high circulating ET-1 levels.

Definition des Kernbereichs ärztlicher Tätigkeit im psychiatrisch-psychotherapeutischen Fachgebiet – Voraussetzung für jede Delegation

Based on legal jurisdiction, knowledge of the psychiatric-psychotherapeutic field and insight into the necessity of a new allocation of responsibilities in the overall therapeutic service of a clinic, the core areas of medical activities are defined for the first time, innovative organisational approaches to the reorganisation of therapeutic service are presented and discussed against the background of qualified staff deficit, introduction of an OPS coding for inpatient psychiatry and economic constraints.