Barbara Hawellek

Noradrenergic modulation of emotion-induced forgetting and remembering.

We used a free-recall paradigm to establish a behavioral index of the retrograde and anterograde interference of emotion with episodic memory encoding. In two experiments involving 78 subjects, we show that negatively valenced items elicit retrograde amnesia, whereas positively valenced items elicit retrograde hypermnesia. These data indicate item valence is critical in determining retrograde amnesia and retrograde hypermnesia. In contrast, we show that item arousal induces an anterograde amnesic effect, consistent with the idea that a valence-evoked arousal mechanism compromises anterograde episodic encoding. Randomized double-blind administration of the β-adrenoceptor antagonist propranolol compared with the selective norepinephrine (NE) reuptake-inhibitor reboxetine, and placebo, demonstrated that the magnitude of this emotional amnesia and hypermnesia can be upregulated and downregulated as a function of emotional arousal and central NE signaling. We conclude that a differential processing of emotional arousal and valence influences how the brain remembers and forgets.

Executive performance of depressed suicide attempters: the role of suicidal ideation

ObjectiveSuicidal ideation has been related to cognitive rigidity whereas suicidal behaviour itself was associated with specific executive deficits. Yet it remains unclear if a distinct cognitive suicidal phenotype does exist. The aim of the present study was to further investigate the role of suicidal thinking for the neuropsychological performance in depressive suicide attempters.MethodDepressive inpatients after a recent suicide attempt, who either had present suicidal ideation (n = 14) or not (n = 15) and healthy controls (n = 29) were recruited. The groups were assessed by means of executive tasks designed to capture impulsive decision-making, and with verbal memory and attention tests. Self-rating measures of impulsivity and aggression were further applied.ResultsOnly patients with current suicidal ideation showed executive dysfunctions with impaired decision-making being the most salient. Verbal memory and attention were reasonably intact in all patients. All patients reported increased aggression.ConclusionSuicidal ideation is clearly associated with impaired cognitive performance. Our results suggest that executive deficits seen in depressive suicide attempters have a state-dependent component.

Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo-controlled, 1-year trial

Objective:  Evidence based on controlled studies is still limited for treatment strategies that prevent recurrence of suicide attempts. Findings from observational as well as meta‐analytic studies strongly suggest that lithium may have suicide‐protective properties.

Upregulation of the Platelet Serotonin2A Receptor and Low Blood Serotonin in Suicidal Psychiatric Patients

Suicidality has been found to be associated with low pre- and postsynaptic serotonin functioning. The purpose of this study was to examine whether in acutely suicidal psychiatric inpatients, the blood serotonin concentration was related to the underlying psychiatric disorder and whether it was associated with changes in the affinity (dissociation constant, KD) or in the maximal binding capacity (Bmax) of the platelet serotonin2A receptor. We therefore determined the blood serotonin concentrations and the platelet serotonin2A receptor activities of 45 suicidal psychiatric patients and 20 healthy subjects. We found that the blood serotonin concentrations were significantly lower in suicidal patients compared to healthy subjects. In all diagnostic categories (affective disorder, schizophrenia and adjustment disorder) we noted a significantly higher maximal binding capacity of the platelet serotonin2A receptor. These findings support the notion that a reduction in the availability of serotonin and an upregulation of the serotonin2A receptors in psychiatric patients are associated with a loss of control over suicidal impulses.

Amygdala control of emotion-induced forgetting and remembering: Evidence from Urbach-Wiethe disease

When presented in a neutral context, emotional items interfere with episodic encoding of temporally contiguous non-emotional items, resulting in dissociable valence-dependent retrograde and arousal-dependent anterograde modulatory effects. By studying two rare patients with congenital lipoid proteinosis (Urbach-Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we demonstrate that this bidirectional modification of episodic encoding by emotion depends on the integrity of the amygdala, as both retrograde and anterograde modulatory effects are absent. Our findings implicate the amygdala in a neural circuitry that orchestrates rapid retrograde and anterograde regulation of episodic memory access upon criteria of behavioral significance.

Enhanced emotion-induced amnesia in borderline personality disorder

BACKGROUND Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion-episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. METHOD To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. RESULTS BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. CONCLUSION These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD.

Suicide prevention by lithium SUPLI--challenges of a multi-center prospective study.

Abstract Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented.

A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

Abstract The subproject 1.5 “Neurobiology of Suicidal Behavior” is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.

Is MAO-B activity in platelets associated with the occurrence of suicidality and behavioural personality traits in depressed patients?

Objective:  Low platelet monoaminoxidase B (MAO‐B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO‐B activity in platelets and aspects of suicidality in depressed patients and controls.

Erniedrigter Serotonin-Turnover ist bei suizidalen depressiven und schizophrenen Patienten von einer kompensatorischen Up-Regulation des Serotonin2-Rezeptors begleitet

Bei suizidalen Patienten ist der Serotonin-(5HT)-Turnover erniedrigt und manifestiert sich als verringerte Konzentration der 5-Hydroxyindol-Essigsaure im Liquor (Asberg et al. 1976). Bei Suizidopfern wird weiterhin prasynaptisch die Reduktion der maximalen Bindung (Bmax) des 5HT-Transporters sowie postsynaptisch eine Erhohung der Bmax des 5HT2-Rezeptors im frontalen Cortex beobachtet (Mann et al. 1986). Diese Erniedrigung des 5HT-Turnovers wird nicht nur zentral, sondern auch peripher als erniedrigte Blut-5HT-Konzentration registriert (Mann et al. 1992, Braunig et al. 1989, Rao et al. 1994). Bei gesunden Probanden reguliert die endogene 5HT-Konzentration im Blut bzw. Thrombozyten kompensatorisch die Affinitat des thrombozytaren 5HT-Transporters und die Bmax des 5HT2-Rezeptors (Meyer-Lindenberg und Rao 1993, Andres et al. 1993). Anhand der vorliegenden Studie sollte die Frage beantwortet werden, ob die bei suizidalen Patienten beobachtete Erniedrigung des Blut-5HTs zu einer kompensatorischen Up-Regulation des 5HT2-Rezeptors auf Thrombozyten fuhrt.