Psychische Erkrankungen in der Lebensspanne ... - DGPPN

Topic 12 G Bildgebung, Neurophysiologie, Neuropsychologie // Brain Imaging, neurophysiology, neuropsychology
cently, it has been proposed as a putative treatment in very treatment
resistant major depression. It might be, that more focused,
targeted treatment approaches that modulating well defined targets
within affective networks in the brain will prove a more effective
approach to help treatment-resistant patients. Deep Brain Stimulation
(DBS) allows the neuromodulation of sites in the brain known
to be implicated in major depression.
Method: We studied antidepressant effects of bilateral DBS to the
nucleus accumbens in ten patients who were included in a protocol
for resistant depression for up to two years. In addition, we recorded
electrophysiological activity from the nucleus accumbens
for two days after implantation
Discussion / Results: DBS induced to significant reduction in depression
severity ratings and neuropsychological improvements. As
of now, it cannot be assumed that DBS will cure treatment refractory
depression. Clinical usefulness of DBS approaches still needs
to be demonstrated convincingly. Hypothesis guided Deep Brain
Stimulation of different targets may reveal more information on the
underlying neurobiology of depression and could be an in teresting
putative new antidepressant approach.
004
Changes in Performance Monitoring after Deep Brain Stimulation
Theo Gründler (MPI f. neurologische Forschung, Köln)
Introduction: Obsessive-Compulsive Disorder (OCD) has been
related to hyperactive cortical-striatal-thalamic pathways. The same
pathways supposed to be engaged in action monitoring manifest in
an event related brain component of electroencephalography – the
error-related negativity (ERN). Larger amplitudes for OCD Pa tients
of this EEG component have reliably been found in numerous studies
using simple forced choice reaction time tasks. Deep brain stimulation
(DBS) is a method used to treat severe and otherwise
treatment-resistant psychiatric disorders. We wanted to test the effect
of DBS in OCD on this cortical-striatal-thalamic pathways and
the ERN as expression of performance monitoring.
Method: To observe the influence of high frequency DBS in the
nucleus accumbens on action monitoring we recorded ERPs from
patients engaged in a forced choice reaction time task. One recording
during high frequency stimulation and one after a twenty-four
hour period without neural stimulation.
Discussion / Results: Preliminary results indicate, that neural stimulation
of the nucleus accumbens leads to a reduced ERN amplitude.
This effect was lasting beyond the twenty-four hours off-stimulation
period. Thus patients after 24 hours without stimula tion
still showed reduced amplitudes compared to a control group. An
effect of plastic subcortical reorganization seems to be the likeliest
source and indicates the sustained therapeutic effect of this form of
treatment in a connected and interacting model of brain connectivity.
Casuistics from a longitudinal study with DBS in the Nucleus
accumbens further support this hypothesis.
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Donnerstag, 26. 11. 2009, 17.15 – 18.45 Uhr, Saal Oslo
S-073 Symposium
Imaging genetics and the neural mechanisms of the major
psychoses
Vorsitz: H. Walter (Bonn), J. Gallinat (Berlin)
001
Genetic risk for major mood disorders and schizophrenia: new
strategies
Andreas Meyer-Lindenberg (ZI für Seelische Gesundheit, Mannheim)
Introduction: While it is clear that the major mood disorders and
schizophrenia and schizophrenia are highly heritable, identifying
mechanisms that mediate this risk, singly or in interaction with the
environment, remains a major challenge.
Method: Imaging genetics is an approach to combine genetic assessment
with multimodal neuroimaging to discover neural systems
linked to genetic abnormalities or variation.
Discussion / Results: Here, we report results obtained from applying
this strategy to candidate genes (DARPP-32, AKT1), and genome-wide
significant variants (ZNF804A, CACNA1C), emphasizing
the delineation of systems defined by convergent data across modalities
and by connectivity, with an emphasis on prefrontal-striatal
and prefrontal-hippocampal interactions. We also discuss mechanisms
of environmental risk for the psychoses. Translational approaches
can identify neural mechanisms of genetic risk for the
major psychoses. Future work should aim at translating these findings
into therapy, and at using intermediate phenotypes in a forward
genetics approach to identify and classify novel risk variants.
002
Functional dysconnectivity and genetic risk for schizophrenia
Christine Esslinger (ZI Mannheim)
P. Kirsch, H. Walter, S. Erk, K. Schnell, L. Haddad, D. Mier, S. H. Witt,
M. Rietschel, S. Cichon, A. Meyer-Lindenberg
Introduction: Recently, a genome wide significant risk SNP (single
nucleotide polymorphism) for psychosis in the gene ZNF804A has
been discovered in a genome wide association study (GWAS)
(O‘Donovan et al., Nat. Genet. 2008) and could be confirmed in
additional independent GWAS (The International Schizophrenia
Consortium, Nature 2009). Because dysconnectivity has been proposed
as possible cause underlying the pathophysiology of schizophrenia,
we investigated the impact of the ZNF804A variant on
functional connectivity within the working memory (WM) network
and could show that during a WM task, healthy risk allele
carriers showed changes in connectivity comparable to that found
in schizophrenia (Esslinger, Walter, Kirsch et al., Science 2009).
However, it was unclear whether this result is cognitively specific or
reflective of a general abnormality of connectivity. Therefore we
tested whether a similar effect could be identified in the WM network
during rest and an emotional control task.
Method: 111 healthy German subjects performed a battery of functional
imaging tasks. Functional connectivity with the right dorsolateral
prefrontal cortex during the WM task, rest and an implicit
emotion recognition task was determined using the seed vox el method.
Discussion / Results: During rest and during the emotional task, a
pattern of reduced interhemispheric connectivity with increasing
number of ZNF804A risk alleles could be seen that was almost
identical to that in the data acquired during the WM task (Fig. 1)
suggesting an influence of the genetic variant on the structural organization
of the brain. By contrast, the abnormal prefronto-hippo-