Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression.

Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

Naturalistic pharmacotherapy of acute episodes of schizophrenic disorders in comparison to treatment guidelines.

INTRODUCTION: This study was designed to investigate to what extent guidelines regarding the pharmacological treatment of patients suffering from schizophrenia-like psychosis are adopted in a naturalistic treatment setting. METHODS: Medical records of n=819 patients undergoing inpatient treatment for schizophrenia-like psychosis in 11 psychiatric hospitals in northwestern Germany were retrospectively analyzed and findings were compared to current schizophrenia guideline recommendations. RESULTS: The prescription rate of second generation antipsychotics increased from 47.1% on admission to 62.5% at discharge. Only half the patients (52.3%) received antipsychotic monotherapy while 47.7% took between 2 and 4 antipsychotic substances at a time. Dosage increases occurred most frequently (in 60%) within the first week of inpatient treatment, 16.6% experienced an elevation between days 15 and 29. A change within the atypical medication was found in 19.3%. Clozapine prescriptions increased throughout the treatment but were combined with other antipsychotic substances in the majority of cases. CONCLUSION: Under naturalistic conditions guideline recommendations for treatment of schizophrenia-like psychosis are adhered to only partially. Combination therapy with 2 or more antipsychotic drugs is quite common despite a clear recommendation for monotherapy.

Effects of quetiapine on cognitive functions in schizophrenic patients: a preliminary single-trial ERP analysis.

AIM: The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment. PATIENTS AND METHODS: Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements. RESULTS: Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0. DISCUSSION: The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.

Audiovisual integration of speech is disturbed in schizophrenia: an fMRI study.

Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.

The myelin-pathogenesis puzzle in schizophrenia: a literature review.

Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

Lamotrigine in the treatment of confusion psychosis. A case report.

We report on the successful treatment of four patients suffering from confusion psychosis according to the classification of Leonhard. The patients did not sufficiently respond to neuroleptic treatment or mood stabilizers like carbamazepine and valproate, but improved when lamotrigine was added, showing a marked reduction in clinical signs and symptoms. The implications of these findings including the possible mechanisms involved are discussed.

Lycanthropy--psychopathological and psychodynamical aspects.

OBJECTIVE: The imagination of being transformed into an animal or being an animal is called lycanthropy. The phenomenon is presented and psychodynamical aspects are discussed. METHOD: A literature review forms the base of this discussion of a psychopathological phenomenon. RESULTS: The lycanthropic symptomatology represents a spectrum of continuity of developmental and culture-dependent normal behaviour via partial forms to the complete picture of lycanthropy. It is observed in different mental disorders. CONCLUSION: Lycanthropy is interpreted by the authors as a delusion in the sense of the self-identity disorder defined by Scharfetter. It is mainly found in affective and schizophrenic disorders but can be a symptom of other psychiatric disorders as well. Psychodynamically this kind of delusion can be interpreted as an attempt to project suppressed affects, especially with aggressive or sexual content, into the figure of an animal. Psychotherapy and/or neuroleptic medication can be effective.

[Oxcarbazepine in the treatment of affective and schizoaffective disorders]. / Oxcarbazepin in der Behandlung affektiver und schizoaffektiver Erkrankungen.

The therapeutic value of anticonvulsants in affective and schizoaffective disorders was documented in several clinical trials. Oxcarbazepine (OXC), a keto-derivative of carbamazepine, which appears to have a preferable side effect profile compared to carbamazepine, has also shown antimanic efficacy in affective and schizoaffective disorders in clinical studies since the early 80's, but was not further investigated regarding these indications. Therefore, the value of OXC in the treatment of affective and schizoaffective disorders requires evaluation. Literature was reviewed with regard to pharmacokinetic and pharmacodynamic characteristics of OXC, drug-drug interactions relevant in pharmacopsychiatry, and clinical effects in these disorders. According to the literature OXC is regarded effective in acute mania and appears to allow reduction of the neuroleptic medication required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to other anticonvulsants and neuroleptics. Furthermore, it appears to be well tolerated if augmented to neuroleptics or antidepressants, since OXC does not interact substantially with the cytochrome P450-enzyme-system. However, despite promising effects of OXC, few clinical studies have been published in the last 16 years. We conclude that further studies should validate the antimanic efficacy of OXC and evaluate possible pharmacopsychiatric indications as well as limitations of this psychotropic compound.

[Paranoia with late onset. Psychopathology and psychodynamics]. / Paranoia mit spätem Beginn. Psychopathologie und Psychodynamik.

We report on a 70-year-old man who suffered from persecutory delusions during the last 20 years. During first visits, he showed neither cognitive impairment nor Schneiderian first rank symptoms. Inpatient and day clinic treatment as well as further outpatient therapy led to reintegration into social life and trusting relationships between the patient and the therapeutic team, although the persecutory delusions still persisted. During following years, symptoms of cognitive impairment increased gradually and neurological symptoms could be observed. We present a psychodynamic hypothesis regarding the reported psychopathology and discuss alternative diagnoses and pharmacological treatment.

Discrepant target detection and action monitoring in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been related to altered mechanisms of action monitoring and target detection, and it has been hypothesized that hyperactive striatal-cortical circuits constitute the underlying pathophysiology. This study used event-related brain potentials (ERPs) to explore this hypothesis. A choice reaction time experiment was carried out in a group of OCD patients and a normal comparison group. The P3b component of the ERP to targets was taken as an indicator of the target-evaluation process and the response-locked error-related negativity (ERN) served as an indicator of action monitoring. We hypothesized that the OCD group would show a shortened P3b latency and an amplitude-enhanced ERN. Consistent with our expectations, the P3b latency was shorter and the ERN amplitude was higher in the OCD group. Unexpectedly, we also observed a prolonged ERN latency in the OCD group and a more posterior topography of this component. The data provide partial support for the hypothesis of a hyperactive neural network in OCD. In addition the disorder must involve pathophysiological processes that are presumably related to other aspects of its complex and heterogeneous clinical hallmarks.

Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies--the key marker triplet determining infection and prevailing in severe mood disorders.

Borna disease virus (BDV), a unique genetically highly conserved RNA virus (Bornaviridae; Mononegavirales), preferentially targets neurons of limbic structures causing behavioral abnormalities in animals. Markers and virus in patients with affective disorders and schizophrenia have raised worldwide interest. A persistent infection was suggestive from follow-up studies, but inconstant detectability weakened a possible linkage.This study for the first time discloses that detection gaps are caused by BDV-specific circulating immune complexes (CIC), and their interplay with free antibodies and plasma antigens (p40/p24). Screening 3000 sera each from human and equine patients over the past 4 years by new enzyme immunoassays (EIAs) revealed that BDV-CICs indicate 10 times higher infection rates (up to 30% in controls, up to 100% in patients) than did previous serology. Persistence of high amounts of CICs and plasma antigens correlates with severity of depression. Even BDV RNA could be detected in plasma samples with strong antigenemia. Our discovery not only explains the course of persistent infection, but offers novel easy-to-use diagnostic tools by which new insights into BDV-related etiopathogenesis of disease and epidemiology are possible.

[Clomethiazole as an adjuvant in the treatment of confusional psychosis]. / Clomethiazol als Adjuvans bei der Behandlung erregt-gehemmter Verwirrtheitspsychosen.

We report on the successful treatment of two female patients with the clinical features of severe confusional psychosis. The clinical picture of these cases was characterized by lability of mood, disorientation, delusions, hallucinations, misidentification of persons, severe thought disorder and impaired memory. A 55-year old female inpatient suffered from a psychotic episode with the clinical features of confusional psychosis. Medical history showed three proceeding confusional psychotic episodes. In the second case a 32-year old female inpatient suffered from a severe postpartum psychosis with the clinical features of confusional psychosis. In this case there was no clinical history of psychotic episodes. After nonresponsive treatment with neuroleptics and mood-stabilizers, both responded rapidly to additional medication with clomethiazole within a week, exhibiting a marked reduction in clinical signs and symptoms. A brief review about this delirium-like psychosis and current knowledge of therapeutic strategies is presented. We discuss clomethiazole as a possible potential adjunct in the treatment of confusional psychoses.

[Lycanthropy-zooanthropism--discussion of a psychopathological phenomenon]. / Lykanthropie/Zooanthropismus--Erörterung eines psychopathologischen Phänomens.

The belief to be transformed into an animal is named Lycanthropy. "Zooanthropismus" is the German equivalent. Three case reports raised the question how this phenomenon, in our cases to be transformed into a frog, a bee or a wolf/dog, can be interpreted in a psychopathological and diagnostic regard. Is it pathognomonic for a special disease? With the three case reports and a survey of the literature this paper deals with Lycanthropy trying to put this perhaps neglected topic back into the focus of psychiatric interest and place it in psychopathology.

Differential effects of emotional content on event-related potentials in word recognition memory.

The aim of this study was to delineate the influence of the emotional content of stimuli to be remembered on the recognition performance of normal subjects by means of the event-related potential (ERP) technique. When words are presented repeatedly, brain responses to repeated and recognized items are characterized by a more positive waveform, referred to as "old/new effect". Words judged for their emotional connotation ("negative", "positive" and "neutral") were presented successively on a video monitor to subjects, who had the task to indicate whether a given word occurred for the first ("new") or second ("old") time within the list by pressing one of two buttons. For each word category, the ERPs of the old words were more positive compared to those of the new items from about 250 ms after stimulus. The old/new effect was significantly enhanced for the negative and positive items compared to the neutral stimuli between 450 and 650 ms after stimulus pointing to a significant influence of the emotional content of words on verbal memory processes. This paradigm appears to be feasible to investigate interactions of emotion and cognition in psychiatric patients.

Oxcarbazepine in affective and schizoaffective disorders.

Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic value in affective and schizoaffective disorders had been documented in several clinical trials. As the authorities in several countries registered newer anticonvulsants with fewer side effects, their therapeutic value in psychiatric disorders was studied. Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine (OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug interactions compared to carbamazepine and other anticonvulsants. Therefore, the value of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated. We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects of OCBZ in the treatment of patients with affective and schizoaffective disorders. According to the literature, OCBZ is regarded as effective in acute mania and appears to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does not interact substantially with the cytochrome P450 enzyme system, co-administration with neuroleptics or antidepressants appears to be well tolerated in affective disorders. However, despite promising effects of OCBZ, few clinical studies have been published in the last 15 years. We conclude that further studies should validate the efficacy of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as well as limitations for this psychotropic compound.

Emotion/cognition-coupling in word recognition memory of depressive patients: an event-related potential study.

Depressive patients show deficits in memory functions. However, the underlying mechanisms remain unclear. Experiments with a special emphasis on the link between emotion and cognition appear challenging. The aim of this study is to investigate the influence of the emotional content of words on memory in non-medicated depressive patients (n=11) compared with a control group (n=11) utilizing event-related brain potentials (ERPs). In a continuous word recognition paradigm brain responses to repeated items are characterized by more positive waveforms of ERPs. This recognition effect ('old/new effect') has been shown to be sensitive to parameters relevant for memory processing. For the purpose of this ERP experiment visually presented words were classified into three different categories of emotional content. The ERPs for the correctly detected 'old' (repeated) words showed an increased positivity beginning approximately 250 ms post-stimulus, concurring with a good recognition performance. In addition, old/new effect and behavioral data were sensitive to words' different emotional connotations in the control group. In contrast, the depressive patients performed worse and showed no significant old/new effect. Nevertheless, their recognition performance was also enhanced by the emotional content. Furthermore, a differential effect of the emotional content on frontal ERPs was found between groups. In contrast to the control group, a reduced old/new effect indicates a reduced working memory capacity in the moderately depressed patients. This is suggested to be partially due to changes of the emotion/cognition coupling related to ruminations with preferably negative emotional connotation. However, the emotional content also affects recognition performance in the depressive patients.