Katrin Radenbach

Muscarinic antagonist effects on executive control of attention

Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.

Nicotinic antagonist effects on functional attention networks

Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.

Thalamic volumes in patients with bipolar disorder.

There are several hypotheses on functional neuronal networks that modulate mood states and which might form the neuroanatomical basis of bipolar disorder. The thalamus has been reported to be a key structure within the circuits that modulate mood states and might thus play an important role within the aetiology of the bipolar affective disorder. Nevertheless, structural brain imaging studies on the thalamus volume of bipolar patients have shown heterogeneous results. Using structural MRI scanning, we compared the thalamus volume of 41 euthymic bipolar patients to the thalamus volume of 41 well-matched healthy controls. Taking the concomitant medication as a co-variable within the patient group, the analysis of variance revealed a significantly smaller relative volume of the right thalamus in patients not treated with lithium when compared with healthy controls. In contrast, there are no significant differences concerning the thalamus volume between all euthymic bipolar patients and healthy controls. The study only shows findings of a transverse section. No longitudinal analysis was performed. More detailed information on patients’ pharmacological histories could not be obtained. In conclusion, this result may be interpreted as an indication of the impact of the thalamus in the pathogenesis of the bipolar I disorder and emphasises the need for further longitudinal studies in bipolar patients with special attention paid to the concomitant medication, in particular to the role of lithium.

Non-therapeutic research with minors: how do chairpersons of German research ethics committees decide?

Objectives: Clinical trials in humans in Germany—as in many other countries—must be approved by local research ethics committees (RECs). The current study has been designed to document and evaluate decisions of chairpersons of RECs in the problematic field of non-therapeutic research with minors. The authors’ purpose was to examine whether non-therapeutic research was acceptable for chairpersons at all, and whether there was certainty on how to decide in research trials involving more than minimal risk. Design: In a questionnaire, REC chairpersons had to evaluate five different scenarios with (in parts) non-therapeutic research. The scenarios described realistic potential research projects with minors, involving increasing levels of risk for the research participants. The chairpersons had to decide whether the respective projects should be approved. Methods: A total of 49 German REC chairpersons were sent questionnaires; 29 questionnaires were returned. The main measurements were approval or rejection of research scenarios. Results: Chairpersons of German RECs generally tend to accept non-therapeutic research with minors if the apparent risk for the participating children is low. If the risk is clearly higher than “minimal”, the chairpersons’ decisions differ widely. Conclusion: The fact that there seem to be different attitudes of chairpersons to non-therapeutic research with minors is problematic from an ethical point of view. It suggests a general uncertainty about the standards of protection for minor research participants in Germany. Therefore, further ethical and legal regulation of non-therapeutic research with minors in Germany seems necessary.

Joint crisis plans and psychiatric advance directives in German psychiatric practice

This study explores the attitude of German psychiatrists in leading positions towards joint crisis plans and psychiatric advance directives. This topic was examined by contacting 473 medical directors of German psychiatric hospitals and departments. They were asked to complete a questionnaire developed by us. That form contained questions about the incidence and acceptance of joint crisis plans and psychiatric advance directives and previous experiences with them. 108 medical directors of psychiatric hospitals and departments responded (response rate: 22.8%). Their answers demonstrate that in their hospitals these documents are rarely used. Among the respondents, joint crisis plans are more accepted than psychiatric advance directives. There is a certain uncertainty when dealing with these instruments. Our main conclusion is that German psychiatry needs an intensified discussion on the use of instruments for patients to constitute procedures for future critical psychiatric events. For this purpose it will be helpful to collect more empirical data. Furthermore, the proposal of joint crisis plans in psychiatric hospitals and departments should be discussed as well as the possibility of consulting an expert during the preparation of a psychiatric advance directive.

„Man kann sich das heute nicht mehr vorstellen, wie die Psychiatrie damals ausgeschaut hat“

1965 veröffentlichte der junge Psychiater Heinz Häfner den Appell: „Dringliche Reformen in der psychiatrischen Krankenversorgung der Bundesrepublik“1, in dem er die menschenunwürdige Situation der Patienten in den deutschen psychiatrischen Anstalten anprangerte. Prof. Dr. med. Dr. phil. Heinz Häfner (geb. 1926) wurde zu einem Wegbereiter der Sozialpsychiatrie in Deutschland und gründete 1975 das Zentralinstitut für Seelische Gesundheit, dessen Direktor er bis 1994 war. Seinen Anstrengungen ist es ganz wesentlich zu verdanken, dass der Bundestag 1971 auf Antrag des Abgeordneten Walter Picard einstimmig beschloss, die Bundesregierung aufzufordern, eine Enquête-Kommission zu berufen. Diese sollte den Stand der Versorgung psychisch Kranker in der BRD untersuchen und Empfehlungen für eine Reform vorlegen. Prof. Häfner hatte den stellvertretenden Vorsitz dieser Kommission, die dieser Aufgabe in den folgenden Jahren nachkam. In diesem Jahr wurde Heinz Häfner 90 Jahre alt.

Family load impacts orbitofrontal volume in first-episode schizophrenia

In schizophrenia, reduced orbitofrontal cortex (OFC) volume is inconsistently reported. To investigate the impact of genetic load on OFC volume, manual MRI-tracing in 23 first-episode schizophrenia patients (FE-SZ) and 23 controls was performed. FE-SZ with genetic load showed a decrease in OFC volume compared to FE-SZ without load and controls.

O-89 Implementing a joint crisis plan into psychiatric practice – first experiences

Background In German psychiatric practice the use of structured advance care planning-instruments is not very common. Standardised joint crisis plans give patients with mental health disorders the opportunity to think ahead for the event of not being able to give informed consent and to perform their autonomy even in those situations. Aim We aimed at avoiding and ameliorating critical situations in our psychiatric hospital by giving patients the opportunity to influence their (emergency-)treatment in situations of incapability to consent to medical care. Furthermore, we wanted to gain experiences with the implementation of a joint crisis plan into clinical psychiatric practice. Methods A joint crisis plan was designed in a trialogic process by psychiatrists, a member of the local clinical ethics committee and deputies of psychiatric patients’ and patients’ relatives support groups. It was offered to selected patients who had experienced periods of incapability to give informed consent due to their psychiatric disease. A quantitative and qualitative evaluation is intended. Results The first experiences with this clinical tool are encouraging. Patients appreciated being able to keep record of their personal know-how and priorities as to the state of their disease. However, some difficulties complicated the implementation of the joint crisis plans into clinical practice. Discussion/conclusion Joint crisis plans are promising as part of a structured advance care planning-program in German psychiatric hospitals. Nevertheless, they need to be embedded into a bundle of arrangements, individually composed for each patient and supported by the clinicians.