Neuropsychologie der Depression : Die Bedeutung von Suizidalität und Impulsivität

Hintergrund: Im Jahr 2000 wurden in der Bundesrepublik Deutschland über 11.000 Suizide registriert, die Zahl der Suizidversuche wird auf 100.000 bis 500.000 geschätzt. Im Rahmen von psychiatrischen Erkrankungen steigt das Suizidrisiko erheblich. So besteht auch bei der Depression eine erhöhte Suizidgefahr. Aktuell wird die Frage diskutiert, inwiefern Suizidalität (im Sinne eines vorangegangen Suizidversuchs) eine eigene Störung bzw. nosologische Entität darstellt und nicht lediglich komorbides Symptom vieler Erkrankungen ist. Insbesondere scheint ein enger Zusammenhang zwischen Suizidalität und überdauernder Impulsivität und Aggression zu bestehen, was auf einen suizidalen Phänotyp hindeutet. Neurobiologisch ist sowohl Suizidalität als auch Impul-sivität und Aggression mit Veränderungen im frontalen Kortex assoziiert, dort insbesondere mit einer gestörten Funktion des orbitofrontalen Kortex. Ebenso werden sowohl Suizidalität als auch Impulsivität und Aggression mit Veränderungen im serotonergen System in Verbindung gebracht. Diese neurobiologischen Überschneidungen legen die Vermutung nahe, dass eine gemeinsame frontale bzw. mit dem serotonergen System assoziierte Störung existiert, die Grundlage oder zumindest wichtiger Bestandteil suizidalen und impulsiven Verhaltens ist. Veränderungen im frontalen Kortex gehen mit Leistungseinbußen im exekutiven Bereich einher. Bisher existieren erst äußerst wenige neuropsychologische Arbeiten, die sich mit Suizidenten (Patienten mit Suizidversuch in der Vorgeschichte) befasst haben. Diese Untersuchungen konnten nicht klären, ob suizidale Patienten ein spezifisches neuropsychologisches Profil aufweisen, das sie von den anderen psychiatrischen Patienten unterscheidet.Methodik: Es wurde in der vorliegenden Studie mithilfe neuropsychologischer und persönlichkeitsbezogener Testverfahren versucht, Unterscheidungsmerkmale zwischen depressiven Suizidenten, depressiven Patienten ohne vorangegangen Suizidversuch und gesunden Probanden zu belegen. Dazu wurden 29 Patienten mit Major Depression, die einen Suizidversuch innerhalb der letzten drei Monate verübt hatten, 29 gesunde Kontrollprobanden und 20 teilremittierte Depressive ohne Suizidversuch in der Vergangenheit untersucht. Um die Heterogenität der Stichprobe zu reduzieren wurden nur unipolar Depressive ohne psychotische Symptome eingeschlossen. Die Wahl teilremittierter Depressiver als klinische Kontrollgruppe erfolgte, weil die Gruppe der Patienten mit einem Suizidversuch innerhalb der letzten drei Monate meist schone mehrere Wochen psychiatrisch behandelt wurden und hinsichtlich der Schwere depressiver Symptomatik ebenfalls teilremittiert waren. Ergebnisse: Erwartungsgemäß waren Aspekte suizidalen Verhaltens mit verschiedenen Facetten von Impulsivität assoziiert. Die Anzahl der bisherigen Suizidversuche korrelierte positiv mit Impul-sivität (Barratt Impulsivitätsinventar), Aggression (Fragebogen für Aggressionsfaktoren) und Ärger (State-Trait-Ärger-Ausdrucksinventar). Hoch impulsive Personen neigten zu Suizidhandlungen, die weniger geplant und potentiell weniger letal waren („Suicide Intention Sca-le“). Patienten, die multiple Suizidversuche verübt hatten, waren impulsiver als die Kontrollpersonen. Wider Erwarten war die klinische Kontrollgruppe der remittierten Depressiven durch eine starke Ärgerdisposition gekennzeichnet und nicht die Suizidenten. Diese unterschieden sich von den remittierten depressiven Probanden durch vermehrt nach innen gerichteten Ärger und Selbstaggression, wobei zu erwähnen ist, dass beide Patientengruppen mehr Ärger nach innen richteten und größere Selbstaggression aufwiesen als die gesunden Kontrollprobanden. Ebenso hatten sie allgemein eine höhere Aggressivität als die gesunden Versuchspersonen. Zusammengenommen schienen Ärger und Aggression nicht per se die entscheidenden Merkmale von Suizidalität zu sein, sondern eher Depressivität zu kennzeichnen. Die Stärke, mit der Patienten diese Emotionen unterdrücken bzw. auf sich selbst richten, war aber charakteristisch für Suizidalität. Bemerkenswert war in diesen Zusammenhang, dass weder Selbstaggression noch nach innen gerichteter Ärger mit der depressiven Symptomatik korreliert waren. Beide Patientengruppen zeigten eine schlechtere verbale Lernleistung als die Kontrollprobanden, jedoch nur die teilremittierten Depressiven hatten ein deutlich schlechteres Langzeitgedächtnis im Vergleich zu der gesunden Stichprobe, was auch in einer verminderten Rekognition zum Ausdruck kam. Das mnestische Profil der Suizidenten entsprach insgesamt nicht dem akut Depressiver und deutete im Gegensatz zu den remittierten Depressiven primär auf eine frontale, nicht aber auf eine temporomesiale Störung hin. Bei den impulsivitätsassoziierten neuropsychologischen Tests konnten die postulierten Defizite bei den Patienten nach Suizidversuch nur teilweise belegt werden: Männliche Suizidenten trafen schlechtere bzw. impulsivere Entscheidungen in der „Iowa Gambling Task“ in der Form, dass sie große Gewinne trotz hoher Verluste kleineren Gewinnen vorzogen, die langfristig ertragreicher wären. In einer „go/no-go“ Aufgabe machten die Suizidenten zwar mehr Auslassungsfehler, nicht aber Fehlreaktionen, welche spezifisch mit Impulsivität in Verbindung gebracht werden. Jedoch begingen sie in der „delayed alternation“ Aufgabe tendenziell mehr Fehler als die gesunden Probanden. Auch im d2 Aufmerksamkeits-Belastungs-Test hatten Suizidenten schlechtere Leistungen als die gesunde Kontrollgruppe. Die remittierten Depressiven wiesen keine exekutiven Defizite auf und lagen in ihren Leistungen numerisch zwischen Suizidenten und gesunden Probanden. Zwischen den klinischen Gruppen bestanden beim direkten Vergleich jedoch keine signifikanten neuropsychologischen Unterschiede.Fazit: Suizidalität lässt sich nicht von Depressivität durch impulsivitätsassoziierte neuropsychologi-sche Tests separieren. Die exekutiven Leistungsschwächen, die die Suizidenten im Vergleich zu den gesunden Probanden zeigten, sind mit dem Vorliegen einer depressiven Episode vereinbar und weisen nicht auf eine orbitofrontalkonzentrierte bzw. impulsivitätsbezogene Dysfunktion hin. Der fehlende Unterschied zwischen den klinischen Gruppen im neuropsychologischen Bereich verdeutlicht außerdem, dass Suizidalität im Rahmen depressiver Störungen zu keinem spezifischen neuropsychologischen Defizit führt. Wesentlich bedeutsamer scheint die mit persönlichkeitspsychologischen Verfahren messbare Steuerung von persönlichen Gefühlen wie Aggression und Ärger zu sein, die im Rahmen einer depressiven Störung verstärkt auftreten. Dabei ist für Patienten mit suizidalen Handlungen kennzeichnend, dass sie diese Emotionen unterdrücken und sehr auf sich selbst richten. Eine erhöhte Impulsivität scheint nur eine Subgruppe von Suizidenten zu charakterisieren, die multiple Suizidversuche unternommen haben. Diese waren in der vorliegenden Untersuchung zahlenmäßig unterrepräsentiert. Zukünftige Studien mit größeren Stichproben könnten durch eine geeignete Subgruppenbildung die Bedeutung von Impulsivität weiter klären. Die verbal mnestischen Defizite der teilremittierten Depressiven fügen sich in das Bild anderer neuropsychologischer Studien ein, die persistierende Gedächtnisdefizite auch bei weitge-hender Remission beschrieben haben.Neuropsychology of Depression - The role of suicidality and impulsivityBackground: In the year 2000, a total of 11.000 suicides was registered in Germany while the number of suicide attempts was estimated to be between 100.000 and 500.000. The risk of suicide is increased for most mental disorders e.g. depressive disorder. At present it remains unclear, whether suicidality (defined by a preceding suicide attempt) represents a distinct disorder, i.e. a nosological entity per se or wether it is merely a comorbid symptom of an underlying psychiatric disease. Associations found between suicidal behaviour and impulsivity and aggression point to a shared suicidal phenotype. Neurobiologically, suicidal behaviour as well as impulsiveness and aggression have been linked with disturbed orbitofrontal function. Additionally, all have been associated with an altered serotonergic transmission. Altogether, these findings suggest a suicidal phenotype based on the disturbed orbitofrontal and serotonergic function. Altered frontal functioning is associated with impaired executive performance. Only very few studies have examined the neuropsychological correlates of suicidal behaviour. Thus it remains unclear, if suicidal patients can be characterized by specific neuropsychological deficits that differ from those typically found in other (non-suicidal) patients with psychiatric disorders.Method: The aim of the present study was to find differences regarding cognitive performance and clinical parameters between depressive suicide attempters, depressive patients without a history of a suicide attempt and healthy controls by means of neuropsychological tests and clinical questionnaires. 29 patients with Major Depression with a history of a suicide attempt within the past 3 months, 29 healthy controls and 20 partly remitted depressive without suicidal behaviour were recruited. In order to minimize clinical heterogeneity of the sample only unipolar depressive patients without past or present psychotic symptoms were included. Clinical controls with partly remitted depression were recruited due to the fact that suicide attempters had already been treated for several weeks with a third of the showing remission.Results: As expected, suicidal behaviour was associated with different levels of impulsivity. The number of suicide attempts showed a positive correlation with impulsivity (Barratt Impulsiveness Scale), aggression (Inventory for the Assessment of Factors of Aggressiveness) and anger (State-Trait Anger Expression Inventory). Highly impulsive suicidal patients tended to plan their last suicide attempt less carefully resulting in reduced potential lethality (Suicide Intent Scale). Multiple suicide attempters were more impulsive compared with healthy controls. Contrary to our expectations, the partly remitted depressive controls but not the suicide attempters yielded the highest disposition for anger. Suicide attempters had higher scores on the suppressed anger and self-directed aggression scales compared with the partly remitted depressives though both groups yielded higher scores in relation to healthy controls. Altogether, anger and aggression seemed to be characteristics of the depressive disease and not indicators of suicidal behavior. The latter might rather be characterized by the self-directedness of anger and aggression. Interestingly, self-directed aggression and suppressed anger were not related to depressive symptoms. Both groups of patients yielded a reduced verbal learning capacity compared with healthy controls though only the partly remitted depressives exhibited significantly impaired long-term memory and recognition in comparison with the healthy participants. On the whole, memory impairment in the suicide attempters differed slightly from those typically seen in Major Depression. Moreover, in opposite to the mnestic dysfunctions of the clinical controls, memory performance of the suicide attempters primarily pointed to frontal and not mesio-temporal changes. The neuropsychological results partly supported the assumptions about an association with increased impulsivity: Male suicide attempters showed an impaired decision-making in the “Iowa Gambling Task”. They preferred huge gains despite of associated huge losses and did not choose small winnings that would have yielded a higher gain in the long run. The whole group of suicide attempters committed more omission errors in a “Go/No-Go Task” compared with healthy controls but not commission errors which are associated with increased impulsivity. Still, suicidal patients tended to make more mistakes in a “Delayed Alternation Task” and performed worse in a letter-cancellation-test compared with healthy controls. The partly remitted depressives without a history of a suicide attempt did not show any executive deficits. Numerically, they performed in-between suicide attempters and healthy participants. There was, however, no difference between suicide attempters’ and remitted depressive patients’ performance.Conclusions: Suicidal behavior can not be distinguished from depressive disorder by means of impulsivity associated neuropsychological tests. The executive deficits of suicide attempters in comparison to healthy controls are in line with cognitive dysfunctions seen in Major Depression and do not indicate a specific orbitofrontal or impulsivity-associated impairment. Furthermore, since suicide attempters and partly remitted depressives did not differ regarding their neuropsychological performance there is no evidence that suicidal behavior among patients with Major Depression does lead to specific neuropsychological deficits. Instead the way patients cope with personal feelings like aggression and anger - as measured with personality questionnaires – could be more important with regard to the identification of suicidal patients. These patients tend to suppress and direct those feelings against their own person. Impulsivity might only be increased in suicide attempters with multiple suicide attempts. There was a lack of this subgroup of suicidal patients in the present study. Future studies consisting of bigger samples may well clarify the role of impulsivity by dividing the patients into reasonable subgroups. Finally, the verbal mnestic deficits of the partly remitted depressives are in accordance with other neuropsychological studies which have reported persistent memory impairment even in the remitted phase of the illness

Occurrence and Distribution of Moganite and Opal-CT in Agates from Paleocene/Eocene Tuffs, El Picado (Cuba)

Agates in Paleocene/Eocene tuffs from El Picado/Los Indios, Cuba were investigated to characterize the mineral composition of the agates and to provide data for the reconstruction of agate forming processes. The volcanic host rocks are strongly altered and fractured and contain numerous fissures and veins mineralized by quartz and chalcedony. These features indicate secondary alteration and silicification processes during tectonic activities that may have also resulted in the formation of massive agates. Local accumulation of manganese oxides/hydroxides, as well as uranium (uranyl-silicate complexes), in the agates confirm their contemporaneous supply with SiO2 and the origin of the silica-bearing solutions from the alteration processes. The mineral composition of the agates is characterized by abnormal high bulk contents of opal-CT (>6 wt%) and moganite (>16 wt%) besides alpha-quartz. The presence of these elevated amounts of “immature” silica phases emphasize that agate formation runs through several structural states of SiO2 with amorphous silica as the first solid phase. A remarkable feature of the agates is a heterogeneous distribution of moganite within the silica matrix revealed by micro-Raman mapping. The intensity ratio of the main symmetric stretching-bending vibrations (A1 modes) of alpha-quartz at 465 cm−1 and moganite at 502 cm−1, respectively, was used to depict the abundance of moganite in the silica matrix. The zoned distribution of moganite and variations in the microtexture and porosity of the agates indicate a multi-phase deposition of SiO2 under varying physico-chemical conditions and a discontinuous silica supply

Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA ("Ecstasy”)

Rationale: In animal studies, the common club drug 3,4-methylendioxymethamphetamine (MDMA, "Ecstasy”) consistently caused a prolonged loss of presynaptic serotonergic neurons, and evidence suggests that MDMA consumption may also affect the human serotonergic system. Serotonin (5-HT) has been implicated in the regulation of impulsivity and such executive functions as decision-making cognition. In fact, MDMA users have shown elevated impulsivity in two studies, but little is known about decision making in drug-free MDMA consumers. Objective: The aim of this study was to examine the cognitive neurotoxicity of MDMA with regard to behavioral impulsivity and decision-making cognition. Methods: Nineteen male, abstinent, heavy MDMA users; 19 male, abstinent cannabis users; and 19 male, drug-naïve controls were examined with the Matching Familiar Figures Test (MFFT) as well as with a Go/No-Go Task (GNG) for impulsivity and with a Gambling Task (GT) for executive functioning. Results: MDMA users showed significantly elevated impulsivity in the MFFT Impulsivity score (I-score), but not in commission errors of the GNG, compared with controls. Cannabis users did not yield altered impulsivity compared with controls. In the GT, MDMA users performed significantly worse than cannabis consumers and controls, whereas cannabis users exhibited the same decision-making capacity as controls. In addition, the I-score as well as the decision-making performance was correlated with measures of MDMA intake. The I-score and the decision-making performance were also correlated. Conclusion: These results suggest that heavy use of MDMA may elevate behavioral impulsivity and impair decision-making cognition possibly mediated by a selective impairment of the 5-HT syste

Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA (“Ecstasy”)

Rationale: In animal studies, the common club drug 3,4-methylendioxymethamphetamine (MDMA, "Ecstasy”) consistently caused a prolonged loss of presynaptic serotonergic neurons, and evidence suggests that MDMA consumption may also affect the human serotonergic system. Serotonin (5-HT) has been implicated in the regulation of impulsivity and such executive functions as decision-making cognition. In fact, MDMA users have shown elevated impulsivity in two studies, but little is known about decision making in drug-free MDMA consumers. Objective: The aim of this study was to examine the cognitive neurotoxicity of MDMA with regard to behavioral impulsivity and decision-making cognition. Methods: Nineteen male, abstinent, heavy MDMA users; 19 male, abstinent cannabis users; and 19 male, drug-naïve controls were examined with the Matching Familiar Figures Test (MFFT) as well as with a Go/No-Go Task (GNG) for impulsivity and with a Gambling Task (GT) for executive functioning. Results: MDMA users showed significantly elevated impulsivity in the MFFT Impulsivity score (I-score), but not in commission errors of the GNG, compared with controls. Cannabis users did not yield altered impulsivity compared with controls. In the GT, MDMA users performed significantly worse than cannabis consumers and controls, whereas cannabis users exhibited the same decision-making capacity as controls. In addition, the I-score as well as the decision-making performance was correlated with measures of MDMA intake. The I-score and the decision-making performance were also correlated. Conclusion: These results suggest that heavy use of MDMA may elevate behavioral impulsivity and impair decision-making cognition possibly mediated by a selective impairment of the 5-HT syste

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled

Combined serotonin-2A (5-HT2A) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10– 20 mg/day) or amisulpride (400–800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT2A/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants