10 research outputs found
A clinical trial in healthy subjects
Titelblatt, Motto, Inhaltsverzeichnis, AbkĂĽrzungsverzeichnis, Danksagung,
Lebenslauf, Erklärung
EinfĂĽhrung
Einleitung
LAAEP als Indikator der zentralen serotonergen Funktion Fragestellung der
Studie
Methoden
Ergebnisse
Diskussion
Zusammenfassung
Literaturverzeichnis
AnhängeDie Lautstärkeabhängigkeit akustisch evozierter Potentiale (LAAEP) wird
gegenwärtig als ein nichtinvasiver und praktikabler Indikator für die zentrale
serotonerge Funktion diskutiert. Eine starke LAAEP zeigt eine niedrige
serotonerge Aktivität an und umgekehrt. Da das serotonerge System an der
Genese zahlreicher psychiatrischer Erkrankungen beteiligt ist, könnte ein
solcher Indikator als ein Hilfsmittel in der Diagnostik und Therapieplanung in
Frage kommen. Direkte Hinweise fĂĽr einen Zusammenhang zwischen der LAAEP und
dem zentralen serotonergen System hat man in Tierstudien gefunden. Da die
Ergebnisse bei Untersuchungen an Menschen jedoch indirekter Natur sind, sollte
in der hier vorliegenden Studie in direkterer Weise der Zusammenhang zwischen
LAAEP und serotonerger Funktion nachgewiesen werden. Es wurde die Hypothese
aufgestellt, dass durch Gabe des SSRI Citalopram, die das Angebot an zentral
verfügbarem Serotonin erhöht, die LAAEP gesunder Probanden eine signifikante
Minderung erfährt. In einem einfachblinden Crossover-Design wurde die LAAEP
von achtzehn weiblichen Probanden unter zwei verschiedenen Bedingungen
gemessen: einerseits bei Infusion von 20 mg Citalopram gelöst in 250 ml
physiologischer Kochsalzlösung, andererseits bei Infusion von 250 ml
physiologischer Kochsalzlösung als Placebo. Die Lautstärkeabhängigkeit wurde
zu fünf verschiedenen Zeitpunkten vor, während und nach der Infusion bestimmt.
Dazu wurden AEP abgeleitet, die die Reaktion auf eine Reihe von Sinustönen mit
unterschiedlichen Schalldruckpegeln darstellten. Aus den Amplituden der am
Punkt Cz gemessenen N1/P2-Komponente wurde die Lautstärkeabhängigkeit
berechnet. Weiterhin wurden diese Skalpdaten mit Hilfe der Dipolquellenanalyse
in die N1/P2-Komponenten des primären und des sekundären akustischen Cortex
aufgespalten. In der statistischen Analyse der ermittelten Daten ergab sich
allerdings kein signifikanter Zusammenhang zwischen der LAAEP und der
Untersuchungsbedingung, also der Gabe von Citalopram oder Placebo. Weder bei
den Skalpdaten noch bei den Daten der tangentialen Dipolaktivität, also
derjenigen des serotonerg innervierten primären akustischen Cortex, konnte die
zuvor aufgestellte Hypothese bestätigt werden. Bei der Bewertung der
Ergebnisse mĂĽssen zahlreiche Einflussfaktoren diskutiert werden. Weibliches
Geschlecht und hormonelle Schwankungen zählen ebenso dazu wie Nikotinabusus
bei den Probanden, Habituationseffekte, Aufmerksamkeitsschwankungen,
Nebenwirkungen des Citalopram und der Untersuchungszeitpunkt. Die Ergebnisse
der vorliegenden Studie können also dahingehend interpretiert werden, dass die
Möglichkeit, die Lautstärkeabhängigkeit der akustisch evozierten Potentiale
als Indikator fĂĽr die zentrale serotonerge Funktion zu verwenden, ein noch
immer umstrittenes Thema darstellt, dessen endgültige Klärung weiterführender
Studien bedarf.The loudness dependence of auditory evoked potentials (LDAEP) has been
discussed as a non-invasive and practicable marker of central serotonergic
function. Large LDAEP represents low serotonergic activity and vice versa.
Since dysfunction of the central serotonergic system is involved in many
psychiatric diseases, such an indicator could be a useful tool for diagnostics
and for planning of therapy. Direct evidence for a relationship between LDAEP
and central serotonergic function has been found in animal studies. As studies
in humans have only provided indirect results, this study aimed to show the
correlation between LDAEP and serotonergic function in a more direct way. It
was hypothesized that administration of the SSRI citalopram, which increases
serotonin availability would cause a significant decrease of the LDAEP in
healthy subjects. In a single-blind cross-over design, the LDAEP of eighteen
female participants was measured under two conditions: (1) infusion of 20 mg
citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9%
saline as a placebo. The loudness dependence was determined at five different
time points before, during and after infusion. For that purpose AEP caused by
stimulation with a randomized series of sinus tones with different sound
pressure levels were recorded. The loudness dependence was calculated using
the amplitudes of the N1/P2 component at Cz. Moreover, dipole source analysis
was used to split the N1/P2 component of the primary and secondary auditory
cortex. The statistical analysis of the data did not reveal a significant
correlation between the LDAEP and the study condition, i.e. administration of
citalopram or placebo. The hypothesis could, therefore, not be confirmed by
either using the scalp data or the tangential dipole activity, the latter
representing the primary auditory cortex with its strong serotonergic
innervation. However, several confounding factors have to be taken into
consideration. Among these, gender and hormonal fluctuation have to be
mentioned as well as abuse of nicotin, effects of habituation, attention, side
effects of citalopram or the time point of the examination. Thus, the results
of this study imply that it is still controversial whether the LDAEP can be
used as a marker of the central serotonergic system. So this needs to be re-
addressed in further studies
Associations between right-hemispheric LDAEP values and clinical characteristics among patients.
<p>Abbreviations: CPZ, Chlorpromazine Dose Equivalence Ratios; PANSS, Positive and Negative Syndrome Scale; SANS, Scale for Assessment of Negative Symptoms; BRMS, Bech-Rafaelsen Melancholia Scale; HAMD, Hamilton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia.</p>*<p>p<0.05.</p
Associations between left-hemispheric LDAEP values and clinical characteristics among patients.
<p>Abbreviations: CPZ, Chlorpromazine Dose Equivalence Ratios; PANSS, Positive and Negative Syndrome Scale; SANS, Scale for Assessment of Negative Symptoms; BRMS, Bech-Rafaelsen Melancholia Scale; HAMD, Hamilton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia.</p>*<p>p<0.05.</p
Does lithium reduce acute suicidal ideation and behavior? : a protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode
Background: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE.
Methods/Design: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome.
Discussion: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment
LDAEP mean values in left and right hemisphere and Cz electrode across groups.
<p>Results are adjusted for age and nicotine use.</p>*<p>p<0.01.</p
The loudness dependence of auditory evoked potentials (LDAEP) as an indicator of serotonergic dysfunction in patients with predominant schizophrenic negative symptoms
Besides the influence of dopaminergic neurotransmission on negative symptoms in schizophrenia, there is evidence that alterations of serotonin (5-HT) system functioning also play a crucial role in the pathophysiology of these disabling symptoms. From post mortem and genetic studies on patients with negative symptoms a 5-HT dysfunction is documented. In addition atypical neuroleptics and some antidepressants improve negative symptoms via serotonergic action. So far no research has been done to directly clarify the association between the serotonergic functioning and the extent of negative symptoms. Therefore, we examined the status of brain 5-HT level in negative symptoms in schizophrenia by means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP provides a well established and non-invasive in vivo marker of the central 5-HT activity. We investigated 13 patients with schizophrenia with predominant negative symptoms treated with atypical neuroleptics and 13 healthy age and gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component was evaluated by dipole source analysis and single electrode estimation at Cz. Psychopathological parameters, nicotine use and medication were assessed to control for additional influencing factors. Schizophrenic patients showed significantly higher LDAEP in both hemispheres than controls. Furthermore, the LDAEP in the right hemisphere in patients was related to higher scores in scales assessing negative symptoms. A relationship with positive symptoms was not found. These data might suggest a diminished central serotonergic neurotransmission in patients with predominant negative symptoms