A. Heiden

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

Rationale and ObjectivesThis study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. MethodsShort-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. ResultsMetabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. ConclusionsThe authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

Genome scan for susceptibility loci for schizophrenia and bipolar disorder

BACKGROUND Despite the widely accepted view that schizophrenia and bipolar disorder represent independent illnesses and modes of inheritance, some data in the literature suggest that the diseases may share some genetic susceptibility. The objective of our analyses was to search for vulnerability loci for the two disorders. METHODS A genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Linkage analyses was used to compute the usual parametric logarithm of the likelihood of linkage (LOD) scores and nonparametric linkage analysis (NPL scores Z(all)) was used to assess the pattern of allele sharing at each marker locus relative to the presence of the disease (GENEHUNTER). Affected status was defined as severe affective disorder or schizophrenia. RESULTS Across the genome, p values associated with NPL scores resulted in evidence (i.e., p <.0007) for linkage at marker D3S1265 on chromosome 3q (NPL score Z (all) = 3.74, p =.0003). Two other markers (on 3q and 6q) showed p values of <.01. CONCLUSIONS We detected a potential susceptibility locus for bipolar disorder and schizophrenia on chromosome 3q, which has not been reported previously. The possibility of a false positive result has to be taken into account. Our data suggest shared loci for schizophrenia and bipolar affective disorders and are consistent with the continuum model of psychosis.

Gender differences in the psychopathology of depressed inpatients

Abstract.In the last few years there has been increased scientific effort to describe the gender–specific psychopathological features of depression. Until now these studies have not been entirely conclusive, which could be the result of methodological difficulties. This report investigates sex differences in the symptom presentation in an inpatient population: 104 female and 113 male patients suffering from a depressive episode according to ICD–10 were admitted to the inpatient treatment at the Department of General Psychiatry in Vienna. A psychopathological rating according to the standardized documentation system of the AMDP (Association for Methodology and Documentation in Psychiatry) was performed at admission and discharge. At admission into the hospital women tended to show more affective lability (p = 0.025), whereas men had higher scores in affective rigidity (p = 0.032), blunted affect (p = 0.002), decreased libido (p = 0.028), hypochondriasis (p = 0.016) and hypochondriac delusions (p = 0.039). At discharge from the hospital women had significantly higher scores in dysphoria (p = 0.010), while men were more prone to have compulsive impulses (p = 0.030). Although our results were obtained in a selected sample of inpatients at a university hospital, they are indicative of psychopathological differences between men and women in the core symptoms of depression. These differences may influence diagnostic practice and gender specific treatment of depression.

Maternal bonding behaviour in schizophrenia and schizoaffective disorder, considering premorbid personality traits

Objective: Bonding between mother and child is described as a complex two-way process ensuring the needs of the child for nurture and protection. As such, it is dependent on the contribution of mother and child [1–3] whereby characteristics of personality of the child may have consequences on maternal bonding behaviour. In the current study the perception of maternal behaviour, premorbid personality traits and relationships between maternal behaviour and personality traits were investigated in schizophrenic and schizoaffective patients and their same-sex, healthy siblings. Methods: We recruited 36 schizophrenic and schizoaffective patients and their same-sex healthy siblings. Information about maternal bonding behaviour was assessed by the Parental Bonding Instrument, information about premorbid personality traits was obtained from their mothers using the ‘Gießen-Test’. Results: Compared to their siblings, patients showed less social resonance, more permeability, less social competence and a more depressed and anxious mood. Furthermore, patients described their mothers to be less caring and to be more overprotective than their siblings described them. But there were strong associations between maternal bonding behaviour and premorbid personality traits. These findings were supported by missing significant differences in maternal care behaviour between patients and siblings when using premorbid characteristics as covariates. Significant high maternal overprotection perceived by patients with schizophrenia and schizaffective disorders still remained after correcting for the influence of premorbid personality traits. Conclusion: The results suggest that premorbid personality traits should be considered not only in analyses of maternal care behaviour in schizophrenic and schizoaffective patients but also when studying other psychiatric patient groups.

Einsatz der Elektrokrampftherapie in der Psychiatrie

ZusammenfassungDie Elektrokrampftherapie (Elektrokonvulsionstherapie, EKT) hat antidepressive und antipsychotische Wirkungen. Seit den ersten Behandlungen (Italien, 1938) ist der Wirkmechanismus ungeklärt geblieben. Die Durchführung wurde in vielerlei Hinsicht modifiziert. Die EKT, bei der durch elektrische Stimulation des Gehirns ein generalisierter epileptischer Anfall ausgelöst wird, erfolgt unter intravenöser Kurznarkose und Muskelrelaxation. Nach sorgfältigen Voruntersuchungen und der Berücksichtigung anästhesiologischer oder internistischer Gegenanzeigen gilt die EKT als sehr sichere Behandlungsform. Persistierende Gedächtnisdefizite wurden nach der früher üblichen bilateralen Applikation von Sinuswellenstrom kasuistisch beschrieben. Durch die Verwendung von Kurzimpulsstrom, die unilaterale Elektrodenplatzierung und die individuelle Dosierung der Ladung (Voraussetzung: EEG-Monitoring) treten Gedächtnisstörungen nach EKT heutzutage seltener auf, und sie remittieren meist komplett innerhalb von 4 bis 8 Wochen. Zur Zeit kommt die EKT insbesondere bei PatientInnen mit therapieresistenten, schwergradigen affektiven oder schizophrenen Störungen zum Einsatz. Die perniziöse Katatonie und das maligne neuroleptische Syndrom stellen eine Notfallindikation dar. Für eine suffiziente EKT ist eine Serie von 6 bis 12 Einzelbehandlungen (jeden 2.–3. Tag) notwendig. Die Responserate bei therapieresistenten Depressionen – zu dieser Indikation gibt es die meisten Daten – ist 50 bis 60%. Dies wird durch eine deskriptive Auswertung aller EKT-Behandlungen an der Psychiatrischen Abteilung der Universitätsklinik Wien, 1994 bis 2000, bestätigt. Ein Bedarf besteht an kontrollierten Studien zur Erhaltungstherapie nach EKT-Serien.SummaryElectroconvulsive therapy (ECT) has antidepressive and antipsychotic effects. Since being introduced in Italy in 1938, its mode of action has still not been clarified. Treatment modalities have changed in many ways. ECT, in which a generalized epileptic seizure is provoked by electrical stimulation of the brain, is performed under short intravenous anesthesia and muscle relaxation. Considering careful previous clinical examination and anesthesiological and internal counterindications, ECT is a very safe form of treatment. Single cases of persisting memory impairment were described after the formerly common bilateral sinus wave stimulation. However, recent developments such as brief pulse stimulation, unilateral electrode placement, and individual stimulus titration (on the basis of EEG monitoring) make memory impairment as a consequence of ECT a rare event which mostly remits completely in 4–8 weeks. Today, ECT is performed mainly in patients suffering from severe, therapy-resistant affective or schizophrenic disorders. Pernicious catatonia and the neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment requires a series of 6–12 individual sessions (every second or third day). In therapy-resistant depression, for which the greatest number of data are available, the response rate lies between 50 and 60%. This has been confirmed by a descriptive analysis of all ECT treatments at the Department of Psychiatry, University of Vienna, between 1994 and 2000. There is a need for controlled studies on continuation therapy subsequent to successful ECT.

Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy

Ten patients with severe, therapy-resistant manic agitation received magnesium sulphate infusions with a continuous magnesium (Mg) flow of approximately 200 mg/h (4353+/-836 mg/day; daily monitored Mg plasma level: 2.44+/-0.34 mmol/l) for periods ranging from 7 to 23 days. Concomitant psychotropic treatment consisted of lithium (n = 10), haloperidol (n = 5) and clonazepam (n = 10). During i.v. Mg treatment the mean values of the maximum dosages of neuroleptics (in chlorpromazine equivalents) and benzodiazepines (in diazepam equivalents) were significantly lower than during the last day of pretreatment (= baseline). Seven patients showed a marked improvement in the Clinical Global Impression scale. In case of bradycardia detected by the ECG monitor (n = 5), Mg flow was reduced and bradycardia disappeared promptly. Mg i.v. may be a useful supplementary therapy for the clinical management of severe manic agitation. This open study needs double-blind confirmation.

Anticipation in schizophrenia

In various genetic disorders it has been observed that the severity of illness increases and the age at onset decreases in successive generations. This phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophrenia spectrum in the index generation in each family (IG; n = 33 affected out of a total of 67 individuals) and in the parental generation (PG; n = 16 affected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant difference between IG and PG regarding severity of illness as defined by Kendler et als hierarchical model of categories of the schizophrenia spectrum (p = 0.001). Age at onset was significantly earlier in the IG (21.6 +/- 6.6 years) than in the PG (40.2 +/- 9.2 years) (p = 0.0001). We excluded a potential birth cohort effect by investigating a control sample consisting of two non-overlapping birth cohorts of patients with schizophrenia. Age at onset between the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular level with special emphasis on trinucleotide repeats might be able to shed further light on this phenomenon.

Bright light therapy in seasonal affective disorder - does it suffice?

Bright light therapy (BLT) has been proposed as treatment of choice for seasonal affective disorder (SAD). However, conventional antidepressants have also been found to be effective in this condition. We examined the psychopharmacologic medication in a clinical sample of 553 SAD patients, who had been treated with BLT, to assess the importance of drug treatment and to critically question the effectiveness of BLT. Forty-nine percent of our patients received psychopharmacologic treatment and about one third (35.4%) was treated with antidepressants, suggesting that BLT does not suffice as only antidepressant regimen for all SAD patients. Furthermore, our results show that only few patients with bipolar affective disorder were willing to accept long-term medication. Opposed to treatment guidelines, patients with several depressive episodes did not receive antidepressant maintenance medication or mood stabilizers more often than patients with only a few episodes.

Pramipexole as adjunct to haloperidol in schizophrenia Safety and efficacy

Pramipexole, a presynaptic dopamine D2/D3 autoreceptor agonist, has been given to haloperidol-treated patients with schizophrenia (n = 15) in an effort to ameliorate residual positive and negative symptoms that have not been satisfactorily influenced by haloperidol alone. Total scores of the positive and negative symptom scale (PANSS) decreased by more than 20% in 9 of 15 patients (reduction of total score: 22-62%). Serious adverse events did not occur. Three of the 15 patients dropped out due to worsening of schizophrenia. Insomnia, as the most frequent side effect, occurred in 4 patients. No clinically relevant electrocardiographic and laboratory changes were reported. This study supports the safety of the treatment of schizophrenia with pramipexole and haloperidol as a combination therapy. However, further clinical studies are required to support these preliminary findings.

Neurodevelopmental Schizophrenia: Obstetric Complications, Birth Weight, Premorbid Social Withdrawal and Learning Disabilities

Neurodevelopmental schizophrenia seems to be caused by impaired cerebral development and is supposed to be associated with obstetric complications (OCs), poor premorbid adjustment, schizotypal or schizoid personality traits and negative symptoms. In the present study, 36 schizophrenic and schizoaffective patients and their same-sex, healthy siblings were recruited. They were diagnosed according to DSM-III-R, using structured psychiatric interviews and a consensus of 2 psychiatrists. Information on OCs, birth weight, premorbid social and learning functioning was obtained from their mothers. The main results show significant differences in OCs, birth weight, premorbid social and learning functioning between patients and their same-sex, healthy siblings. Using multivariate analyses, both premorbid variables were again identified to discriminate well between affected and unaffected siblings. Our findings seem to confirm the concept of schizophrenia as a neurodevelopmental process.