Estradiol levels in psychotic disorders.

Estradiol has been postulated to constitute a protective factor for schizophrenia, which could provide women at risk to experience a psychotic episode with a relative protection in phases of high estradiol levels, i.e. before menopause and during the peri- and postovulatory phases of their cycle. Women suffering from schizophrenia have been reported to show significantly lower estradiol levels than the normal population and to experience first onset or recurrence of a psychotic episode significantly more often in low estrogen phases of the cycle with low estradiol levels. We examined estradiol levels in an open prospective study in 43 women admitted with a diagnosis of an acute psychotic episode and could confirm these findings for schizophrenia as well as other psychotic disorders. Only 28% of the women exhibited estradiol and progesterone levels indicating a peri- or postovulatory phase and all of the estradiol levels on admission were either within the lower part of the cycle-dependent normal range or below normal; comparison with a control group of healthy volunteers and patients admitted with different psychiatric diagnoses confirmed their estradiol levels to be significantly higher. However, when splitting this control group, the statistical difference would only hold between the study group of psychotic patients and the healthy control group. The group of patients with other diagnoses than a psychotic episode fell in between of the other two groups and did not differ significantly from either. Thus, an unspecific effect, i.e. a hypothalamic downregulation due to the stress of acute hospitalization must be born in mind when assessing hormone levels in acutely psychotic women.

Reduced binocular depth inversion in schizophrenic patients.

Binocular depth inversion represents an illusion of visual perception, serving to invert the perception of implausible hollow objects, e.g. a hollow face into a normal face. Such inversion occurs frequently, especially when objects with a high degree of familiarity (e.g. photographs of faces) are displayed. Under normal conditions, cognitive factors apparently override the binocular disparity cues of stereopsis. This internal mechanism--a kind of "censorship" of perception balancing "top-down" and "bottom-up" processes of perception--appears to be disturbed in psychotic states. The clinical and neuropsychological performance of schizophrenic patients was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive And Negative Symptoms Scale (PANSS), the Clinical Global Impression Scale (CGI), the Mehrfach-Wahlwortschatz Intelligence Test (MWT-B) and the binocular depth inversion test (BDIT) using pictures with a high degree of familiarity. In schizophrenic patients, the performance in the BDIT differed significantly from healthy controls and from patients with major depression. The schizophrenic patients were more veridical in their judgements in the BDIT. During antipsychotic treatment, BPRS and PANSS scores improved and the inversed faces were seen as more illusionary, driven by an increase in top-down processing. At the end of treatment, there was no significant difference between the patient group and the healthy controls in the score of binocular depth inversion. These findings suggest that testing of binocular depth inversion can detect specific dysfunctions in visual perception and might be useful as a state-marker for psychotic states.

High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients.

Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in major depression. In order to investigate the therapeutic efficacy of rTMS in psychotic patients, 12 participants (four women, eight men) with schizophrenia according to DSM-IV criteria, aged 25 to 63 years (mean (+/-s.d) 40.4+/-11.0), were enrolled in the study. Following a double-blind crossover design, patients were treated at random with 2 weeks of daily left prefrontal rTMS (20 2s 20 Hz stimulations at 80% motor threshold over 20 min, dorsolateral preforntal cortex) and 2 weeks of sham stimulation. The Brief Psychiatric Rating Scale decreased under active rTMS (p <0.05), whereas depressive symptoms (BDI) and anxiety (STAI) did not change significantly. Prefrontal rTMS might be effective in the non-pharmacological treatment of psychotic patients.

Buprenorphine and carbamazepine as a treatment for detoxification of opiate addicts with multiple drug misuse: a pilot study.

The growing tendency of opioid addicts to misuse multiple other drugs leads to the investigation of new pharmacostrategies to prevent patients from suffering life-threatening complications and minimize the withdrawal symptoms. The short-term efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15) to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled 21-day inpatient detoxification treatment was compared. Twenty-seven men and women dependent on opioids and misusing other drugs admitted to a detoxification unit were included in this protocol. Eighteen of 27 patients (67%) completed the study. Four non-completers (27%) received buprenorphine/carbamazepine (four of 15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five of 12), but the difference in the dropout rate between the two treatment strategies was not significant.The buprenorphine/carbamazepine regime provided significantly more effective relief of withdrawal symptoms during the first week of treatment. No severe side effects occurred during treatment in both groups. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than oxazepam/carbamazepine in rapid opioid detoxification in patients with additional multiple drug misuse and both regimens were safe with no unexpected side effects.

Antibodies to bacterial L-asparaginases.

Complement fixation has been shown to occur when asparaginase reacts with specific antibody. This is as a result of an antigenic determinant common to the four bacterial asparaginases. Patients on asparaginase therapy may produce antibodies and these could be demonstrated by complement fixation.

Sexual impairment in psychiatric inpatients: focus on depression.

INTRODUCTION: Although sexual side effects are a common reason for noncompliance with medication, information on impairment of sexuality in psychiatric inpatients is scarce. METHODS: In the present multi-center study, data on several aspects of sexual functioning were collected in psychiatric inpatients using a previously validated questionnaire. RESULTS: A high overall prevalence of sexual dysfunction was reported by participants and was highest in depressed subjects. Patients receiving antidepressants suffered from more frequent and more severe impairment of sexuality than did subjects receiving neither antidepressants nor antipsychotics or opioids. DISCUSSION: Judging from this data, sexual impairment appears to be a frequent and underestimated problem in psychiatric inpatients with a high prevalence across all diagnostic groups, particularly in depressed subjects. Female patients attribute this impairment mainly to their mental illness, whereas male patients tend to assign their impairments primarily to their medication.

Sexual dysfunction in psychiatric inpatients the role of antipsychotic medication.

INTRODUCTION: Sexual dysfunction is a common side effect of antipsychotic medication. Although increased prolactin levels caused by antipsychotic agents are believed to play a major role with regard to sexual side effects, the underlying mechanism of antipsychotic agent-induced sexual dysfunction remains poorly understood. METHODS: In a multicentric study 587 psychiatric inpatients were assessed by means of a self-rating sexual questionnaire. Focussing on antipsychotic treatment three subgroups were drawn from the original sample. One group was treated with prolactin-increasing antipsychotics (n=119), the other with prolactin-neutral medication (n=109) and the third patient group was comprised of non-medicated clinical controls (n=105). RESULTS: The majority of all patients (50-75%) reported at least minor sexual dysfunction. On comparison of the subgroups, only female patients treated with prolactin-increasing medication reported more severe sexual dysfunction. However, multiple regression analysis did not confirm an association between the type of treatment and sexual impairment. DISCUSSION: Sexual dysfunction frequently occurs in psychiatric inpatients treated with antipsychotics. Our findings only partly support the assumptions concerning a major role of prolactin-increasing neuroleptics for medication-induced sexual impairment.

[Inpatient treatment of depression. Should one combine psychotherapy and drugs?]. / Stationäre Depressionsbehandlung. Soll man Psychotherapie und Medikamente kombinieren?

Antidepressants as well as different psychotherapeutic strategies have been proven efficacious in the treatment of unipolar depression. In the clinical setting both are often combined using psychotherapeutic methods varying from psychoeducation to formal psychotherapy. The present article provides a critical overview of the evidence base for this combination in the inpatient treatment of depression. The current literature is contradictory and difficult to compare. However, combination therapy appears advantageous in therapy-resistant, chronic and severe forms of depressive disorders. Much further research is needed to facilitate well-founded guidelines.

Possible use of amantadine in depression.

Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.

Psychotic disorders and gonadal function: evidence supporting the oestrogen hypothesis.

OBJECTIVE: The aim of this study was to further evaluate the oestrogen hypothesis of schizophrenia, which postulates low oestradiol levels to be a risk factor for these disorders. A possible influence of neuroleptic-induced hyperprolactinaemia was to be addressed. METHOD: Sex hormones were measured and cycle phase assessed in 50 acutely psychotic women on admission and for four consecutive weeks as well as in three control groups. RESULTS: Psychotic women were more likely to be admitted during a low oestrogen phase of their cycle and exhibited markedly reduced oestradiol levels, compared with 23 healthy controls, as well as 50 women suffering from other psychiatric disorders. Oestradiol variability was reduced over the menstrual cycle in women suffering from psychotic disorders. CONCLUSION: These results support the oestrogen hypothesis. Hyperprolactinaemia due to neuroleptic treatment does not appear to account for the findings.

Specific IgM class antibody production following infection with cytomegalovirus.

Specific IgM class antibody production was studied in different groups of patients with characterized cytomegalovirus (CMV) infections using a radioimmunoassay (RIA). In pregnant women, IgM antibodies were detected only following primary infection and generally persisted less than 4 months. The demonstration of CMV-specific IgM during pregnancy is therefore diagnostic of recent primary CMV infection. In patients with symptomatic CMV infections, the appearance of IgM antibody was shown to be closely related to the onset of symptoms and coincided with production of complement fixing (CF) antibody. IgM antibodies were at maximum levels 3-4 weeks after presentation but generally declined to low or undetectable levels by 3-4 months. The significance of the results of testing for CMV-specific IgM in relation to clinical and other serological findings in these patients is discussed. IgM antibody production was also demonstrated in renal transplant patients with primary infections and in 6 of 21 recipients with secondary infections. In both groups the antibodies became detectable 3-6 weeks after transplantation but the titres were much higher following primary infection. IgM antibodies persisted throughout follow-up periods of up to 2 years after transplantation in some cases.

A syndrome of psychosis following discontinuation of an estrogen-progestogen contraceptive and improvement following replacement: A case report.

Mild forms of psychosis associated with low estrogen levels during the perimenopause are relatively frequent. There is scarce data on severe forms of psychosis in these conditions. We report the case of a 51-year-old woman with no previous psychiatric history who amputated her hand in a 'psychotiform' state after discontinuation of her contraceptive medication. Having subsequently jumped out of a window, she suffered a fracture of the dens with central spinal cord injury and symptoms of cruciate paralysis. The patient stabilized under a combined therapy with estrogen-progestogen substitution, antipsychotic medication and add-on oxcarbazepine.

Combination therapy with nefazodone and lithium: Safety and tolerability in fourteen patients.

Fourteen patients with major depression, resistant to previous pharmacotherapies, were treated by the addition of lithium (target range 0.6-0.8 mmol/l) to nefazodone (≥400 mg/day) and were prospectively monitored for 6 weeks to assess safety and tolerability. There were 42 emergent adverse events-most commonly headache, nausea, gastro-intestinal disturbances, tremor, polyuria/polydipsia, dry mouth and tiredness. Information on ten additional patients receiving combined treatment with lithium and nefazodone was collected by retrospective chart review, and it was found that similar adverse events (tremor, dry mouth and tiredness) had occurred in these patients. We conclude that when lithium is added to nefazodone, new adverse events do occur, but that the treatment is safe and tolerable.

Aromatic metabolism in the fungi. Growth of Rhodotorula mucilaginosa in p-hydroxybenzoate-limited chemostats and the effects of growth rate on the synthesis of enzymes of the 3-oxoadipate pathway.

Rhodotorula mucilaginosa was grown in p-hydroxybenzoate-limited chemostats over the dilution rate (D) range 0.01 to 0.17 h-1 and growth was adequately described by the Monod theory when maintenance energy requirements were considered. The p-hydroxy-benzoate affinity constant, K8, had the relatively high value of 270 mg/I. The yield from p-hydroxbenzoate varied with dilution rate but was constant above D equal 0.07 h-1 at 0.56 g yeast/g substrate utilised. The maintenance coefficeint for growth on the aromatic substrate was 20 mg/g yeast/hr. Culture viability decreased linearly as the dilution rate was reduced. 4-Hydroxybenzoate 3-mono-oxygenase, protocatechuate 3,4-dioxygenases, 3-carboxymuconate cyclase and 3-carboxymuconolactone hydrolase activities were dilution rate-dependent, results which accord with the substrate in inducibility of these enzymes. Under carbon-limited growth conditions the addition of glucose, a catabolite repressor of these enzymes, to the aromatic medium stimulated their synthesis. Data were also obtained which indicated that whereas the synthesis of the cyclase and the hydrolase was coordinately controlled, that of the first two enzymes of the 3-oxodipate pathway was under independent control.

Word recognition memory before and after successful treatment of depression.

One of the most frequent and neuropsychologically well investigated symptoms in depression is reduced memory capacity. In this study, we investigated the course of disease in 16 patients with moderate depression and Borna disease virus (BDV) infection. Recently, it could be shown that BDV infection might play an important role in the etiology of subtypes of depression. Amantadine treatment was used as an antidepressant and antiviral compound. In order to assess memory capacity, event-related potentials (ERPs) were evaluated in ten of sixteen patients in a continuous word recognition experiment using a series of emotionally neutral, positive or negative words. During the treatment period the patients' clinical condition improved significantly. ERPs showed a reduced old/new effect before and after treatment independent of the words' emotional content. These findings suggest a reduced memory capacity being relatively independent of clinical outcome and ability to use emotional connotations for memory mechanisms. However, a significant positive shift over frontal electrodes did occur, which was concomitant with the improvement of depression, suggesting evidence for changed frontal cortical activity.

Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial.

OBJECTIVE: Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. In addition. only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV-infected depressive patients was investigated. METHODS: In this open trial, amantadine was added to antidepressive and or mood-stabilizing compounds treating BDV-infected depressed patients (n = 25) with bipolar or major depressive disorders. Amantadine was given twice a day (100-300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM-D) and/or with an operationalized diagnostic criteria system (OPCRIT: version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples. RESULTS: The overall response rate of the amantadine augmentation in the BDV-infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity. CONCLUSION: Amantadine appears to show a remarkable antidepressive efficacy in BDV-infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.

Outcome and comorbidity in first- compared with multiple-episode mania.

The aim of this study was to examine the outcome and comorbidity of patients with bipolar disorder presenting with first-episode as compared with multiple-episode mania. Based on studies from the prepharmacological era and the sensitization model of bipolar disorder, we hypothesized that compared with multiple-episode mania, first-episode mania would be associated with better outcome, milder severity, and less psychiatric comorbidity. Seventy-one hospitalized patients, age 12 years and older and meeting DSM-III-R criteria for bipolar disorder, were recruited over a 1-year period. Thirty-four (48%) first-episode and 37 (56%) multiple-episode patients were compared regarding demographics, phenomenology, comorbidity, family history, and short-term course. Compared with multiple-episode mania, first-episode mania was associated with significantly shorter hospitalization and a higher rate of comorbid impulse control disorders. These data provide indirect support for the sensitization model of bipolar disorder.

Reduced binocular depth inversion in patients with alcoholism.

Binocular depth inversion represents an illusion of visual perception, serving to invert the perception of implausible hollow objects, e.g. a hollow face into a normal face. Such inversion occurs frequently, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. The hypothesis was tested that during mild and moderate alcohol withdrawal, and severe and mild alcohol intoxication, the central nervous system is unable to correct implausible perceptual hypotheses. Measurements of binocular depth inversion in perception of three-dimensional objects were performed in 10 patients with severe alcohol intoxication, in 10 subjects with mild alcohol intoxication, in nine patients with moderate alcohol withdrawal treated with carbamazepine, in 10 patients with moderate alcohol withdrawal without any pharmacological treatment, in 11 patients with mild alcohol withdrawal and in 10 healthy volunteers. The binocular depth inversion scores were highly elevated in the severely intoxicated patients group and in the group with moderate withdrawal symptoms without carbamazepine treatment, in comparison to the healthy volunteers. The data demonstrate a strong impairment of binocular depth inversion in moderate alcohol withdrawal and during severe alcohol intoxication. This supports the view that these states may be accompanied by a disorganization of the interaction between sensory input and top-down component. The effects of carbamazepine are discussed.