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ZusammenfassungAus Sicht der forensischen Kliniken werden durch die Justiz immer häufiger einstweilige Unterbringungen nach § 126a StPO angeordnet. Es werden drei Hypothesen aufgestellt, die diese Zunahme (mit)erklären könnten: 1) Anordnung auch bei Bagatellfällen. 2) Anordnung trotz positiver Prognose. 3) Verändertes Anzeigeverhalten der psychiatrischen Kliniken. Einfache Erklärungsansätze für die Zunahme der einstweiligen Unterbringungen greifen jedoch zu kurz. Umso dringlicher erscheint eine Stärkung des primärpräventiven Ansatzes. Bereits in der allgemeinpsychiatrischen Versorgung sollte der kleine Teil Menschen mit psychischer Erkrankung und erhöhter Gewaltbereitschaft erkannt und einer gewaltpräventiven Behandlung zugeführt werden. Forensische Psychiatrie und allgemeinpsychiatrische Versorgung müssen sich dafür enger verzahnen.

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics.Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index.167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed.Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Executive dysfunctions (regarding behavioural inhibition, decision making, flexibility or voluntary selection) rank among the core symptoms of attention deficit/hyperactivity disorder. Several studies demonstrated functional variations in patients with ADHD especially during response inhibition and flexibility. However, information about functional correlates of other aspects of executive functions such as voluntary selection processes is limited. A group of thirty adult patients with attention deficit/hyperactivity disorder (ADHD) and 30 healthy controls, matched for age and education, participated in the present study. Electrophysiological responses (event-related potentials, gamma oscillations) and behavioural data were acquired during the voluntary selection between various response alternatives. ADHD patients demonstrated increased responses in the gamma frequency band especially in frontal and fronto-central brain areas during voluntary response selection processes compared to healthy subjects. In addition, the error rate was increased in patients. Given that gamma-band responses have been related to GABAergic and glutamatergic responses these results may indicate accordant dysfunction in patients with ADHD.

The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP’s. We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment. This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.

Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.

Evidence suggests that neurocognitive impairment is a key factor in the pathology of schizophrenia and is linked with the negative symptoms of the disease. In this study the effects of the atypical antipsychotics quetiapine and risperidone on cognitive function in patients with schizophrenia and with predominantly negative symptoms were compared. Patients were randomly assigned to double-blind treatment with quetiapine or risperidone for 12 weeks. Cognitive function was assessed at baseline, Week 6 and Week 12. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline, Week 6 and Week 12. Extrapyramidal side-effects were assessed each week using the Simpson-Angus Scale (SAS), adverse events were recorded as additional indicators of tolerability throughout the trial. In total, 44 patients were enrolled in the study. Data from the 34 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 6 and Week 12) are analysed here. Quetiapine improved significantly global cognitive index z-scores at both Week 6 (p

Pathomechanisms of schizophrenia comprise a wide range of neurobiological alterations including dopaminergic dysfunction. Aim of the study was to investigate dopaminergic neurotransmission in subjects with schizophrenia, individuals at risk for the development of a first episode of psychosis, and healthy controls. A dynamic IBZM SPECT protocol was used to assess endogenous dopamine release following an amphetamine challenge. Subjects underwent a SPECT study using a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed two hours after bolus injection, and one hour following amphetamine challenge (0.3mg/kg i.v.). Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. Upon amphetamine challenge mean IBZM binding decreased by about 4.9(±7.6)% in healthy subjects (n=7) as compared to a mean 13.4(±6.3)% in 6 subjects with schizophrenia (p

Executive functions comprise various cognitive abilities including the inhibition of prepotent responses and voluntary decisions. Several studies showed medial-frontal activations in tasks with the free selection of responses. The inhibition of prepotent response tendencies seems to be associated with medial frontal as well as lateral frontal BOLD responses. The aim of this simultaneous EEG and fMRI study was to discriminate the neural correlates of behavioural control processes in ADHD.8 adults with ADHD and 8 matched healthy subjects performed a go/nogo task comprising three different conditions: during the go condition, subjects were instructed to press a response button as fast as possible; during the nogo condition, this response was to be inhibited. In the voluntary selection task participants were allowed to freely decide, whether to press the response button or not.The fMRI protocol used a gradient-echo EPI pulse sequence. Further analyses were done with using the BrainVoyager software package (Goebel, Maastricht). EEG signals were simultaneously recorded (Brain Products, Munich).Electrophysiologically, the nogo task and voluntary decision task led to a negative decline especially in fronto-central brain regions (N2) in both groups. Regarding the functional MRI data we found inhibition-associated BOLD responses especially medial-frontal in the pre-SMA and activations in the medial part of BA 8 for the voluntary selection. ADHD patients showed a reduced contribution of frontal brain regions during free responses compared to controls.The results may indicate that selection processes are related with dysfunctions predominantly in frontal brain regions in ADHD patients.

IntroductionPatients with impulse control deficits often show cognitive abnormalities especially in executive abilities. One possibility to examine the underlying neurophysiological mechanisms is to assess evoked potentials. In the present study an adapted go/nogo-paradigm was used to investigate electrophysiological correlates of voluntary selection and behaviour control processes in patients suffering from alcohol dependence and attention deficit hyperactivity disorder (ADHD).Methods15 patients with alcohol dependence, 15 adult patients with ADHD and 15 control persons were included into the study. Patients with alcoholism were examined twice: before and after an inpatient detoxification.The participants performed a go/nogo task, comprising three different conditions:Apart from the go-condition (button press required) and the nogo-task (inhibition of a behavioural response), a voluntary selection task was included in which participants were allowed to freely decide, whether to press the response button or not.Results and discussionResponse inhibition and voluntary selection processes were related to a fronto-central negativity after 200 ms (N2) and a positivity after 300 ms (P3) in healthy subjects. In patients, the P3 amplitude was reduced compared to the controls. In addition, alcohol dependent patients did not show a N2 potential.The results indicate fronto-central dysfunctions dysfunctions in either patient group. However, different neuronal processes seemed to be affected in patients with ADHD and patients with alcoholism.