Koen Schruers

Deep Brain Stimulation in Tourette's Syndrome: Two Targets?

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette’s syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro‐oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS.

The effects of tryptophan depletion on mood and psychiatric symptoms

Abstract Background: The number of studies using tryptophan depletion (TD) challenge has increased markedly in the past few years. Recently, a number of negative results have been published, implicating that the effect of TD on mood may be less consistent than previously thought. Methods: The literature on the mood effects of TD in psychiatric patients and healthy volunteers was reviewed. Results: TD has a mood-lowering effect in subgroups of recovered depressed patients, patients with seasonal affective disorder and vulnerable healthy subjects. The mood effect in former patients is of a different quality, however, than the effect in healthy subjects. Some recent negative studies in depression might be explained by insufficient lowering of plasma tryptophan levels. Preliminary evidence exists for an effect of TD on bulimia nervosa, autism, aggression and substance dependence. Conclusions: The effects of TD on mood may be more consistent than suggested by a number of recent negative studies. Response to TD in recovered depressed patients is associated with prior treatment. However, even in SSRI-treated patients the relapse rates are not higher than 50–60%, which needs to be explained. The clinical usefulness of the response to TD in recovered patients (prediction of relapse after treatment discontinuation) and in symptomatic patients (prediction of treatment refractoriness) deserves more research attention. Further suggestions for future research include the cognitive effects of TD in recovered depressed patients and the effect of dietary habits on response to TD.

Resilience in mental health: linking psychological and neurobiological perspectives

To review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies.

Amygdala hyperfunction in phobic fear normalizes after exposure

BACKGROUND The amygdala is implicated as a key brain structure in fear processing. Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses. As such, fear extinction could be expected to induce a reduction in amygdala activity. However, exposure in specific phobia has never been shown persistently to reduce amygdala activity. METHODS By means of event-related functional magnetic resonance imaging, responses to phobia-related, general threat, and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects. RESULTS Phobic subjects showed increased amygdala activity at baseline. This hyperactivity was significantly reduced 2 weeks after exposure therapy. Furthermore, a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure. CONCLUSIONS To our knowledge, this is the first study demonstrating the effect of exposure on the amygdala in specific phobia. Our findings suggest that exposure therapy can have an effect on subcortical structures.

Experimental pathophysiology of panic

In this article, we review how the knowledge of the pathophysiology of panic disorder has expanded, with special emphasis on laboratory models using lactate and carbon dioxide challenges. Experiments in the late 1960s revealed that lactate infusion can induce panic attacks. A prominent feature of these attacks is hyperventilation. Because lactate infusion induces a metabolic alkalosis, one would rather expect a compensatory hypoventilation. For years hyperventilation was thought to be causally linked to panic, but it has since been proven to be a symptom rather than a cause of panic attacks. Similarly, it is not hypocapnia but hypercapnia that has proven to be capable of provoking panic attacks. Carbon dioxide challenges are comparable to lactate infusion in the degree to which they meet the criteria for an ideal model of panic disorder. Experiments with carbon dioxide in first-degree relatives of panic disorder patients and in monozygotic twins support the idea of a constitutional predisposition to panic disorder. Of the various other agents that have been used to trigger panic attacks, cholecystokinin seems particularly promising as a valid laboratory model of panic disorder and may provide valuable data regarding the mechanism of panic attacks. The false suffocation alarm theory, proposed by Klein, is an integrative hypothesis that may account for a large number of the laboratory as well as clinical observations.

Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients

Results of an earlier study in healthy volunteers suggest that the serotonergic system is involved in anxiety-related mechanisms. We studied the influence of tryptophan depletion on the response to a 35% carbon dioxide challenge. Twenty-four panic disorder patients received a mixture of amino acids, either with or without tryptophan, under double-blind conditions. There was a significant increase in anxiety as well as in neurovegetative symptoms in the depletion group, compared to the placebo condition. Furthermore, when we compare the results of the placebo group with earlier panic provocation studies, it also seems that a balanced amino acid mixture might have a protective effect against a panic provocation. We conclude that the panic-enhancing effect of tryptophan depletion as well as the potential protective effect of tryptophan administration in panic disorder patients can be explained by the Deakin-Graeff theory of anxiety.

Obsessive-compulsive disorder: a critical review of therapeutic perspectives.

Objective:  Obsessive–compulsive disorder (OCD) is a chronic disabling disease with profound implications for social functioning. Thirty per cent of all patients with OCD show insufficient improvement with state‐of‐the‐art treatment. Conventional treatment and alternative treatment options for this population were investigated.

A therapeutic application of the experience sampling method in the treatment of depression: a randomized controlled trial

In depression, the ability to experience daily life positive affect predicts recovery and reduces relapse rates. Interventions based on the experience sampling method (ESM‐I) are ideally suited to provide insight in personal, contextualized patterns of positive affect. The aim of this study was to examine whether add‐on ESM‐derived feedback on personalized patterns of positive affect is feasible and useful to patients, and results in a reduction of depressive symptomatology. Depressed outpatients (n=102) receiving pharmacological treatment participated in a randomized controlled trial with three arms: an experimental group receiving add‐on ESM‐derived feedback, a pseudo‐experimental group participating in ESM but receiving no feedback, and a control group. The experimental group participated in an ESM procedure (three days per week over a 6‐week period) using a palmtop. This group received weekly standardized feedback on personalized patterns of positive affect. Hamilton Depression Rating Scale – 17 (HDRS) and Inventory of Depressive Symptoms (IDS) scores were obtained before and after the intervention. During a 6‐month follow‐up period, five HDRS and IDS assessments were completed. Add‐on ESM‐derived feedback resulted in a significant and clinically relevant stronger decrease in HDRS score relative to the control group (p<0.01; −5.5 point reduction in HDRS at 6 months). Compared to the pseudo‐experimental group, a clinically relevant decrease in HDRS score was apparent at 6 months (B=−3.6, p=0.053). Self‐reported depressive complaints (IDS) yielded the same pattern over time. The use of ESM‐I was deemed acceptable and the provided feedback easy to understand. Patients attempted to apply suggestions from ESM‐derived feedback to daily life. These data suggest that the efficacy of traditional passive pharmacological approach to treatment of major depression can be enhanced by using person‐tailored daily life information regarding positive affect.

Selective processing of social stimuli in the superficial amygdala

The human amygdala plays a pivotal role in the processing of socially significant information. Anatomical studies show that the human amygdala is not a single homogeneous structure but is composed of segregable subregions. These have recently been functionally delineated by using a combination of functional magnetic resonance imaging (fMRI) and cytoarchitectonically defined probabilistic maps. However, the response characteristics and individual contribution of these subregions to the processing of social‐emotional stimuli are little understood. Here, we used this novel technique to segregate intra‐amygdalar responses to facial expressions and nonsocial control stimuli. We localized facial expression‐evoked signal changes bilaterally in the superficial amygdala, which suggests that this subregion selectively extracts the social value of incoming sensory information. Hum Brain Mapp, 2009.

Acute l-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients

Previous research showed that lowering the availability of serotonin to the brain by tryptophan depletion increases the vulnerability of panic disorder patients for an experimental 35% CO(2) panic challenge. The results also suggested that increased availability of serotonin inhibits the response to such a challenge. In the present study, this latter possibility is examined. The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% CO(2) panic challenge was assessed following administration of 200-mg L-5-hydroxytryptophan (the immediate precursor of serotonin) or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.