Introduction Deprivation is widely known in children and adolescents and means a lack of social, emotional, or sensory stimuli, due to disabilities such as deafness, but also social isolation and reduced parental care. It may cause developmental disorders such as impaired language, motoric and social development. Little is known of the impact of social deprivation in demented patients.Stimulus shielding, which is a widespread option for psychiatric symptoms of dementia such as agitation, vocalization and aggressive behavior may – if frequently used- have similar effects on demented patients. Objectives We report the case of a 71-year-old patient with dementia caused by PSP (Progressive Supranuclear Palsy), who was in inpatient treatment due to continuous undirected vocalizations. She presented with inability to walk, dysarthria, aphasia, and hearing difficulties beside major mnestic impairment. In a prior hospitalization and in her residency, she was frequently isolated from other patients due to loud screaming and vocalizations in terms of stimulus shielding by suspected overstimulation. In order to that, for four months, she developed progressive difficulties to speak, hear, understand, as well as gait disorders. In addition, the vocalizations increased. Methods We rated the symptoms due to deprivation, triggered by lack of mobilization, social experiences, visual, tactile and acoustic stimuli following a vicious circle of anxiety, vocalizations and recurrent isolations. Therefore, a multimodal therapy assessment was implemented, including daily physical therapy, mobilization, basal stimulation, social reintegration and basal conversation training. Results After a few days of high intensity treatment, speech reappeared in form of one- word sentences and proceeded to the ability to have short conversations. Mobility increased, starting from severe gait disorder, including the use of a wheelchair and emerged to the ability of walking up to 50 metres. Additionally, the undirected vocalizations improved and were reduced. In addition, hearing ability improved during the four-week treatment. Conclusions This case highlights the impact of deprivation in demented patients. Especially it shows that these symptoms can be reversible under a high intensity multimodal and multi- professional treatment within a few weeks. Therefore, stimulus shielding, should be carefully evaluated in order to prevent deprivation – and thus deterioration of the symptoms – in demented patients. Disclosure of Interest None Declared

Despite heritability estimates of 37–69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene.

Isotretinoin, the 13-cis isomer of all-trans-retinoic acid, is a retinoid and thus a derivative of vitamin A. It has been used successfully since the 1980s to treat severe recalcitrant nodular acne [Sundstrom et al. 2010], but various case reports have suggested that isotretinoin is associated with depression and suicidal behaviour [Citrome, 1998; Hazen et al. 1983; Wysowski and Swartz, 2005] and manic psychosis [Barak et al. 2005]. To the best of the authors’ knowledge, there have been hardly any reports of psychosis during treatment with isotretinoin.

Humour involves the ability to detect incongruous ideas violating social rules and norms. Accordingly, humour requires a complex array of cognitive skills for which intact frontal lobe functioning is critical. Here, we sought to examine the association of facial expression during an emotion inducing experiment with frontal cortex morphology in healthy subjects. Thirty-one healthy male subjects (mean age: 30.8 +/- 8.9 years; all right-handers) watching a humorous movie ("Mr. Bean") were investigated. Markers fixed at certain points of the face emitting high-frequency ultrasonic signals allowed direct measurement of facial movements with high spatial temporal resolution. Magnetic resonance images of the frontal cortex were obtained with a 1.5-T Magnetom using a coronar T2- and proton-density-weighted Dual-Echo-Sequence and a 3D-magnetization-prepared rapid gradient echo (MPRAGE) sequence. Volumetric analysis was performed using BRAINS. Frontal cortex volume was partly associated with slower speed of "laughing" movements of the eyes ("genuine" or Duchenne smile). Specifically, grey matter volume was associated with longer emotional reaction time ipsilaterally, even when controlled for age and daily alcohol intake. These results lend support to the hypothesis that superior cognitive evaluation of humorous stimuli mediated by larger prefrontal grey and white matter volume-leads to a measurable reduction of speed of emotional expressivity in normal adults. (C) 2010 Elsevier Srl. All rights reserved.

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages. A total of 319 inpatients and healthy controls were enrolled and investigated with magnetic resonance imaging (MRI). Hippocampal volumes were measured using the segmentation software BRAINS. Bilateral hippocampal volume reductions were detected in both schizophrenic and depressed patients compared to healthy control (HC) subjects. Although younger, schizophrenic (SZ) patients showed in their MRI scans significant bilaterally reduced hippocampal volumes compared to patients with major depression. Although the hippocampal reductions were similar at the onset of symptomatic manifestation of both diseases, there was a further significant reduction of the left hippocampus in the recurrently ill SZ subgroup. The data suggest rather dynamic structural brain alterations in schizophrenia compared to major depression. Here, the presented application of the comparative neuroscience approach, by the use of large neuroimaging MRI databases, seems highly valuable. In the field of psychiatry, with its still controversial operationalized descriptive diagnostic entities, the cross-nosological approach provides a helpful tool to better elucidate the still unknown brain pathologies and their underlying molecular mechanisms beyond a single nosological entity.

Despite important recent advances, a full understanding of the (genetic) etiology of Alzheimer's disease (AD) is still a long way off. Large collaborative efforts are ongoing, as well as the exploration of various sources of genetic variation. Evidence supports the view that Mendelian early-onset familial forms of AD are caused by rare and usually highly penetrant mutations in three genes (APP, PSEN1 and PSEN2). Considering sporadic late-onset AD (LOAD), the APOE epsilon 4 allele is by far the best-established risk gene. Recently published large-scale genome-wide analyses point to additionally relevant genetically associated loci, particularly CLU, PICALM and CR1. These susceptibility loci support existing hypotheses about the amyloid, lipid, chaperone and chronic inflammatory mechanisms in AD pathogenesis, and are therefore likely to provide the basis for the development of hypothesis-driven novel biomarker candidates. Additional genes, listed online in AlzGene (e.g., GAB2 or SORL1) have repeatedly shown risk effects in LOAD, and may be true risk genes, but this is much less certain. New epigenetic research provided some evidence that DNA modifications maybe involved in LOAD (e.g., post-mortem studies described both hypo- and hyper-methylation in AD-related susceptibility genes). With respect to biomarkers, elderly nondemented APOE epsilon 4 carriers demonstrated distinct cerebrospinal fluid biomarker signatures and alterations of brain glucose metabolism similar to those observed in AD. Future research should evaluate the usefulness of newly detected AD risk genes and epigenetic changes as potential biomarkers towards genetic profiling of AD or for correlation with endophenotypes and therapeutic outcome.

The anterior cingulate cortex (ACC) is located at the rostum of the corpus callosum and involved in both cognitive and emotional brain processes. It has been suggested to be involved in P300 event-related potential generation. A large sample of schizophrenia inpatients and controls was examined in order to assess the potential relationship between ACC volumes and P300 characteristics in patients with more pronounced negative symptoms. In 50 male schizophrenia patients and 50 matched controls, auditory P300 and structural magnetic resonance imaging volume measurements of the ACC were obtained. Patients' negative symptoms were assessed using the PANSS (Positive and Negative Syndrome Scale). Volumetry of ACC subregions revealed a volume reduction in patients with schizophrenia compared with controls in right hemispheric rostral ACC subregions that were most pronounced in more negative schizophrenia patients. There was a positive correlation between PZ P300 amplitude and total ACC volume in the right hemisphere in schizophrenia patients with less negative symptoms. The results support the assumption that structural changes of the ACC are more pronounced in subgroups of schizophrenia patients with more negative psychopathology. In addition, while right hemisphere ACC volumes significantly differ between schizophrenia subgroups, combining measures of event-related potential (ERP) and ACC volumetry does not add additional information.

CONTEXTIdentification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging-based diagnostic classification of neuropsychiatric patient populations.OBJECTIVETo determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level.DESIGNMultivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs.SETTINGDepartments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.PARTICIPANTSThe first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs.MAIN OUTCOME MEASURESSpecificity, sensitivity, and accuracy of classification.RESULTSThe 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases.CONCLUSIONSDifferent ARMSs and their clinical outcomes may be reliably identified on an individual basis by assessing patterns of whole-brain neuroanatomical abnormalities. These patterns may serve as valuable biomarkers for the clinician to guide early detection in the prodromal phase of psychosis.

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates. Therefore, gray matter density (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy control subjects (HC) were examined in a three-step approach using cross-sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of structural alterations irrespective of symptomatology; (2) subdivision of the patient sample according to a three-dimensional factor model of the PANSS and investigation of structural differences between these subsamples and healthy controls; (3) analysis of a common pattern of structural alterations present in all patient subsamples compared to healthy controls. Significant GMD reductions in patients compared to controls were identified within the prefrontal, limbic, paralimbic, temporal and thalamic regions. The disorganized symptom dimension was associated with bilateral alterations in temporal, insular and medial prefrontal cortices. Positive symptoms were associated with left-pronounced alterations in perisylvian regions and extended thalamic GMD losses. Negative symptoms were linked to the most extended alterations within orbitofrontal, medial prefrontal, lateral prefrontal and temporal cortices as well as limbic and subcortical structures. Thus, structural heterogeneity in schizophrenia may relate to specific patterns of GMD reductions that possibly share a common prefrontal-perisylvian pattern of structural brain alterations.

BACKGROUND:In recent years, in vivo and post-mortem studies detected structural brain changes in schizophrenia. The aim of our analysis was to investigate potential changes of white matter in schizophrenic patients compared to controls, and the relationship to clinical characteristics.METHODS:Fifty male, right-handed schizophrenic patients who met DSM-IV criteria for schizophrenia were recruited. Fifty right-handed, age- and sex-matched subjects without a psychiatric disorder were enrolled as controls. Volumes of white matter in several brain regions were measured by 1.5 T MRI using a volumetry and segmentation software (BRAINS). Regions of interest including frontal, temporal, parietal, occipital and subcortical areas were determined using Talairach spaces.RESULTS:No significant differences in white matter volumes of total brain tissue and regions of interest were detected between patients and controls. A significant reduction of white matter in parietal cortex of right hemisphere was found in a subgroup of patients with pronounced negative symptoms. Furthermore, patients with first-grade relatives suffering from schizophrenia showed a reduction of subcortical white matter in the right hemisphere.CONCLUSIONS:Our results indicate that subgroups of schizophrenic patients show alterations of white matter in distinct brain regions, including the right parietal lobe.

The anterior cingulate cortex (ACC) is involved in the regulation of emotion processing, and its volume has been found to be reduced in patients with major depression. Furthermore, larger ACC volumes have been associated with faster symptom improvement under therapy. The aims of the study were to examine whether volumes of the anterior cingulate cortex are altered and are related to the clinical course of major depression. Subjects comprised 78 inpatients with major depression and 78 age-, gender- and handedness- matched healthy volunteers, who were investigated with structural magnetic resonance imaging (MRI). The ACC was subdivided into the subgenual, pre-callosal, rostral-anterior and caudal-anterior ACC. No significant differences were observed for ACC volumes between patients and healthy controls. Left ACC volumes showed a significant negative correlation with the number of hospitalizations. These findings suggest that ACC volumes are not altered in patients with major depression, but that patients with larger ACC have a better clinical outcome than patients with smaller ACC.

Proposing cognitive impairment in working memory (wm) functions as a cognitive core deficit in schizophrenia, 23 first episode, medication-free schizophrenic patients in a comparison of healthy adults have been investigated by fMRI. Additionally, the effects of different attentional demands in wm tasks were analysed. A wm paradigm was applied, in which stimuli were presented in a 2-back and a 0-back condition in a non-degraded and degraded version. As hypothesized in healthy controls increased activity during both 2-back tasks was found in the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), parietal regions, the thalamus and the cerebellum. Different activation patterns were found for the cingulate cortex in the 2-back degraded conditions. The comparison between healthy controls and schizophrenic patients revealed decreased activity in the right VLPFC in patients as well as increased activity in temporal regions. Furthermore patients' task performance quality was significantly lower for 2-back conditions. Schizophrenic patients use different cognitive strategies to solve working memory tasks, reflected in significantly altered cerebral activity. However, the different fMRI working memory correlates found in schizophrenic patients seem to be insufficient in terms of overall task performance.

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine(1A) receptor (5-HTR1A) gene C - 1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program 'BRAINS'. Patients who have the 5-HTR1A gene G allele had significantly smaller amygdala volumes than C/C genotype carriers (P = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR1A genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression (P = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR1A gene C - 1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.

Fragestellung: Arbeitsgedächtnisleistungen als Teilbereich der exekutiven Funktionen scheinen bei schizophrenen Erkrankungen eine Schlüsselfunktion zu besitzen. Funktionelle MRT Studien an diesem Patientenkollektiv belegen eine Störung kortikaler, subkortikaler als auch zerebellärer Regionen. Kognitive Disorganisation und Aufmerksamkeitsdefizite als typische psychotische Symptome werden als Konsequenz einer neuronalen Dyskonnektivität postuliert. Ziel der Studie lag in der Verlaufsmessung zerebraler Aktivierungen schizophrener Patienten nach einer 12-wöchigen psychopharmakologischen Behandlung mit dem Atypika Quetiapin.

Fragestellung: Die Verarbeitung nonverbaler emotionaler und sozialer Stimuli stellt die Grundlage der alltäglichen Kommunikation dar. Die Wahrnehmung und Interpretation emotionaler Gesichtsausdrücke kann sowohl auf einer expliziten als auch impliziten Ebene erfolgen. Das Ziel der Studie bestand in der Untersuchung der für explizite und implizite unterschiedlichen Hirnregionen mittels funktioneller Kernspintomographie.

Fragestellung: Eine Vielzahl struktureller Studien zur Schizophrenie belegt fokale volumetrische Veränderungen als neurobiologisches Korrelat dieser psychiatrischen Erkrankung.