[Trauma and memory-A contribution to the current debate in law and psychotherapy]. / Trauma und Erinnerung ­ ein Beitrag zur aktuellen Debatte in Recht und Psychotherapie.

The recall of memories of past events, experiences and emotions is a complex process. When experiencing traumatic events, as is the case with sexual violence, a host of additional complexities and difficulties arise. This becomes especially important in court cases which rely mostly or exclusively on the testimony of the victim, where the problem of the fallibility of memory takes center stage. Some research studies emphasize the possibility of inducing, altering or suppressing memories, especially in the context of psychotherapy. This has led to the unfortunate reality that the testimony of victims who have undergone psychotherapy is often considered to be unreliable. This in turn can lead to the impression that a decision has to be made between treatment of the adverse effects of traumatic events and maximizing the chances for a conviction of the perpetrator in court. This article introduces some central concepts of our current understanding of memory and gives an overview of the relevant scientific literature and debate. Following this, it examines the dilemma as it pertains to the different groups of all involved parties (i.e., victims, members of the judiciary and psychotherapists). Lastly, it proposes a framework of how to approach a solution to this problem by focusing on research in critical areas, expansion of therapy guidelines and documentation procedures as well as communication of these efforts to all parties involved.

Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.

Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia.

Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia.

Schizophrenia is a severe neuropsychiatric disorder with familial loading as heritable risk factor and cannabis abuse as the most relevant environmental risk factor up to date. Cannabis abuse has been related to an earlier onset of the disease and persisting cannabis consumption is associated with reduced symptom improvement. However, the underlying morphological and biochemical brain alterations due to these risk factors as well as the effects of gene-environmental interaction are still unclear. In this magnetic resonance imaging (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control subjects, we investigated effects of previous cannabis abuse and increased familial risk on subcortical brain regions such as hippocampus, amygdala, caudate nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a subsequent single-volume (1)H-magnetic resonance spectroscopy study, we investigated spectra in the left hippocampus and putamen to detect metabolic alterations. Compared to healthy controls, schizophrenia patients displayed decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus as well as an increased area of the midsagittal CC1 segment of the corpus callosum. Patients fulfilling the criteria for cannabis abuse at admission showed an increased area of the CC2 segment compared to those who did not fulfill the criteria. Patients with a family history of schizophrenia combined with previous cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to all other patients, implicating an interaction between the genetic background and cannabis abuse as environmental factor. Patients with cannabis abuse also had higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a possible neuroprotective effect in this area. However, antipsychotic medication prior to MRI acquisition and gender effects may have influenced our results. Future longitudinal studies in first-episode patients with quantification of cannabis abuse and assessment of schizophrenia risk genes are warranted.

Pattern and volume of the anterior cingulate cortex in chronic posttraumatic stress disorder (PTSD).

Evidence suggests that the anterior cingulate cortex (ACC) plays a key role in the development of posttraumatic stress disorder (PTSD). Owing to the region's highly variable patterns, three different studies of PTSD have yielded inconsistent volume reductions. Accordingly, in order to measure the correct borders and volumes, the different patterns of the ACC must be considered separately. We examined 15 victims with chronic symptoms of PTSD, all traumatized at the same accident in 1988, comparing them to 15 matched control subjects. After categorizing the ACC according to single, single segmented, double or double segmented cingulate sulcus (CS), we measured the area with a semi-automated procedure using Brain2 software. Fifty-three percent of our PTSD subjects had single segmented CS compared to 23% in control subjects and 25% in the literature. Furthermore, the four patterns showed differences in mean volume over all subjects of up to 13%. We detected no differences in absolute ACC volumes when differentiating between the patterns or in correlation with brain volumes or clinical parameters. This is the first study to differentiate ACC structure into different patterns in PTSD. We found that one pattern was overrepresented which, in turn, could signal vulnerability to develop PTSD. Because of the remarkable volume differences between patterns, future studies should categorize this highly variable region into different patterns for volumetric measurements. However, future investigations in larger samples should confirm our findings and assess to which extend alterations of ACC patterns may influence the incidence of PTSD.

Decreased reelin expression in the left prefrontal cortex (BA9) in chronic schizophrenia patients.

BACKGROUND: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. METHODS: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. RESULTS: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. CONCLUSION: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples.

Alpha-2-delta ligands for singultus (hiccup) treatment: three case reports.

Chronic idiopathic singultus (hiccup) is a debilitating condition affecting mostly elderly males. While in the past, pharmacologic singultus treatment was mostly "trial and error," more recently, treatment has become both more evidence based and pathophysiology guided. A combination of an acidity-reducing drug (H(2)-receptor blocker or proton pump inhibitor) with baclofen (gamma-amino-butyric-acid receptor type B agonist) has become the most widely used regimen. Some clinicians replace or supplement baclofen with gabapentin. We present three cases of chronic idiopathic hiccup managed with gabapentin or another alpha-2-delta ligand, pregabalin. This is the first reported use of pregabalin for this indication.

Retrieval and emotional processing of traumatic memories in posttraumatic stress disorder: peripheral and central correlates.

Posttraumatic stress disorder (PTSD) is thought to be characterized by dysfunctional memory processes, i.e., the automatic re-experiencing of the traumatic event and the inability to consciously recall facts about the traumatic event, as well as altered emotional processing of trauma-relevant cues. The present study examined the cerebral mechanisms underlying the cued recall of trauma-specific memories and the emotional processing of the presented cues in 16 PTSD patients, 15 trauma-exposed subjects without PTSD and 16 healthy controls. Subjects received questions about their specific trauma as well as other disastrous and neutral events while the electroencephalogram and heart rate were measured. The PTSD patients showed no impairment in trauma-specific declarative memory compared to non-PTSD subjects but had some deficits in general declarative memory as assessed by the Wechsler Memory Scale-Revised. Compared to healthy control subjects, PTSD patients displayed increased P300 and late positive complex amplitudes to trauma-specific questions, indicating enhanced emotional processing of these cues. In line with their behavioral performance, both trauma-exposed groups showed decreased terminal contingent negative variation amplitudes to trauma-specific questions over frontal electrodes reflecting altered memory retrieval. Within-group comparisons revealed that only the PTSD group but not the other groups showed a differentiation between trauma-specific and neutral questions with respect to the LPC, tCNV and P300. Concordantly with previous studies, PTSD patients showed elevated resting heart rate compared to the healthy controls. These findings are discussed in the context of current models of the role of declarative memory in the development and maintenance of PTSD.

Altered thalamic membrane phospholipids in schizophrenia: a postmortem study.

BACKGROUND: Membrane lipids are important mediators of neuronal function. In a postmortem study, we measured membrane lipid components in the left thalamus of schizophrenic patients. This region might play an important role in the pathophysiology of schizophrenia and has not been studied thus far with respect to its membrane lipid composition. METHODS: The study included 18 chronic schizophrenic patients and 23 healthy control subjects. Using lipid extraction and thin-layer chromatography, we measured membrane phospholipids, galactocerebrosides 1 and 2, and sulfatides in thalamus homogenate. RESULTS: The main membrane phospholipid phosphatidylcholine and the major myelin membrane components sphingomyelin and galactocerebrosides 1 and 2 were found to be decreased in schizophrenic patients. In contrast, phosphatidylserine was increased. These lipid contents did not correlate with postmortem intervals and medication doses. There was no difference in the membrane phospholipids lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylglycerol or in sulfatides. CONCLUSIONS: Our results confirm findings of magnetic resonance imaging, postmortem, and gene expression studies. They support the notion of an increased phospholipid breakdown in schizophrenia as a sign for decreased myelination and oligodendrocyte dysfunction.

Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

[Mnestic impairment under olanzapine overdosage in an elderly patient]. / Mnestische Störungen unter Olanzapinüberdosierung bei einem älteren Patienten.

Atypical antipsychotics are increasingly used for the treatment of elderly patients. However, there are only few studies on their efficacy and side effects in this patient group. The case of a 67-year old patient is presented, in whom under treatment with olanzapine in usual dosage, serum level increased into the toxic range. This olanzapine overdosage was accompanied by severe impairments in visual and verbal memory and by an increase of slow-frequency activity in the EEG. Both alterations may be attributed to the anticholinergic effects of olanzapine and reversed rapidly after dose reduction and normalization of the olanzapine serum level.

Effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits.

Postmortem studies in schizophrenic patients revealed alterations in NMDA receptor binding and gene expression of specific subunits. Because most of the patients had been treated with antipsychotics over long periods, medication effects might have influenced those findings. We treated animals with haloperidol and clozapine in clinical doses to investigate the effects of long-term antipsychotic treatment on NMDA receptor binding and gene expression of subunits. Rats were treated with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day) given in drinking water over a period of 6 months. Quantitative receptor autoradiography with [3H]-MK-801 was used to examine NMDA receptor binding. In situ hybridization was performed for additional gene expression studies of the NR1, NR2A, NR2B, NR2C, and NR2D subunits. [3H]-MK-801 binding was found to be increased after haloperidol treatment in the striatum and nucleus accumbens. Clozapine was shown to up-regulate NMDA receptor binding only in the nucleus accumbens. There were no alterations in gene expression of NMDA subunits in any of the three regions. However, the NR2A subunit was down-regulated in the hippocampus and prefrontal cortex by both drugs, whereas only clozapine induced a down-regulation of NR1 in the dorsolateral prefrontal cortex. NR2B, 2C, and 2D subunits did not differ between treatment groups and controls. Both altered NMDA receptor binding and subunit expression strengthen a hyperglutamatergic function after haloperidol treatment and may contribute to some of our postmortem findings in antipsychotically treated schizophrenic patients. Because the effects seen in different brain areas clearly vary between haloperidol and clozapine, they may also be responsible for some of the differences in efficacy and side effects.

Disfunção pré-frontoparietal durante o processamento de informação visuoauditiva em pacientes idosos com esquizofrenia crônica e efeitos da medicação / Parieto-prefrontal dysfunction during visuo-auditory information processing in elderly, chronic schizophrenic patients and medication effects

OBJETIVOS: Em pacientes com primeiro episódio de esquizofrenia, estudos com ressonância magnética funcional (RMf) têm demonstrado disfunção pré-frontoparietal durante estimulação acústica e visual. O objetivo do presente estudo foi investigar a rede pré-frontoparietal em pacientes idosos com esquizofrenia utilizando o mesmo paradigma. Adicionalmente, foram presumidos efeitos favoráveis na ativação cerebral pelo antipsicótico atípico clozapina em comparação a neurolépticos típicos. MÉTODOS: Foram investigados 18 pacientes com esquizofrenia crônica e 21 controles saudáveis idosos. Nove pacientes com esquizofrenia haviam sido medicados com clozapina e nove haviam recebido neurolépticos típicos por décadas. Concomitantemente às avaliações com escalas psicopatológicas e neuropsicológicas foi utilizado um paradigma de estimulação auditiva e visual em um aparelho de ressonância magnética de 1,5 Tesla para investigar a resposta BOLD em diferentes áreas cerebrais. RESULTADOS: Comparados a controles saudáveis, os pacientes com esquizofrenia apresentaram diminuição na ativação cerebral nos córtices pré-frontal e parietal, assim como no giro do cíngulo anterior medial. Nessas regiões, os pacientes medicados com clozapina apresentaram resposta BOLD aumentada em comparação aos pacientes tratados com neurolépticos típicos. DISCUSSÃO: O presente estudo confirmou a presença de distúrbios na rede pré-frontoparietal em pacientes idosos com esquizofrenia, apontando assim para a preservação de déficits de ativação cerebrais e a influência de distúrbios do desenvolvimento neural em esquizofrenia crônica até a velhice. CONCLUSÃO: O antipsicótico atípico clozapina parece facilitar a ativação de áreas cerebrais mesmo em pacientes idosos com esquizofrenia crônica.

OBJECTIVES: In first-episode schizophrenia patients, functional magnetic resonance imaging (fMRI) has shown prefronto-parietal dysfunction during acoustic and visual stimulation. The aim of this study was to investigate the prefronto-parietal network in elderly schizophrenia patients using the same paradigm. Additionally, we hypothesized favourable effects on brain activation by the atypical antipsychotic clozapine compared to typical neuroleptics. METHODS: We investigated 18 elderly, chronic schizophrenia patients and 21 elderly healthy controls. Nine schizophrenia patients had been medicated with clozapine and 9 had been receiving typical neuroleptics over decades. In addition to assessments with psychopathological and neuropsychological rating scales we used an acoustic and visual stimulation paradigm in a 1.5 Tesla MRI scanner to investigate BOLD-response in different brain areas. RESULTS: Compared to healthy controls schizophrenia patients showed decreased brain activation in the prefrontal and parietal cortex as well as medial anterior cingulate gyrus compared to healthy controls. In these regions, patients medicated with clozapine showed increased BOLD-response compared to patients treated with typical neuroleptics. DISCUSSION: Our study confirmed prefronto-parietal network disturbances in elderly schizophrenia patients thus pointing to the preservation of brain activation deficits and the influence of neurodevelopmental disturbances in chronic schizophrenia until old-age. CONCLUSION: The atypical antipsychotic clozapine seems to facilitate brain activation even in elderly, chronic schizophrenia patients.