Eric Griez

CO2 vulnerability in panic disorder.

The immediate effects of a single inhalation of a 35% CO2 mixture in oxygen were examined in 12 patients with panic disorders and 11 normal control subjects. Compared to a placebo air inhalation, the CO2 inhalation provoked short-lived autonomic panic symptoms in both patients and normals; it also elicited high subjective anxiety in patients with panic disorders. The latter rated the overall CO2-induced state as very similar to a real-life panic attack.

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.

Specific sensitivity of patients with panic attacks to carbon dioxide inhalation

One inhalation of 35% CO2 in oxygen was administered to 36 patients with anxiety disorders and 14 healthy controls. Eighteen patients had a diagnosis of panic disorder (PD) and 18 of obsessive-compulsive disorder (OCD). As a placebo control for CO2, compressed air was administered in a double-blind design. Immediately before and after the inhalation, levels of anxiety and DSM-III-R symptoms of panic were assessed. CO2 elicited high levels of subjective anxiety in the PD group. Patients with OCD were hardly affected by the inhalation, and did not differ from healthy controls. These results suggest that CO2 challenge should be considered as a specific probe for subjects with panic-anxiety. It is speculated that CO2 may trigger some as yet undefined mechanisms, possibly linked to ventilation control, which demarcate panic from other types of pathological anxiety.

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.

Co2 inhalation in the treatment of panic attacks

If panic disorder is conceptualized as a fear of interoceptive sensations, it can be treated by exposure to the autonomic symptoms that are induced by CO2 inhalation. In a cross-over study of 14 patients, propranolol was used as a control treatment. CO2 produced a significant reduction of fear of autonomic panic sensations, state and trait anxiety, agoraphobic anxiety and avoidance, and of the frequency of panicking. Propranolol resulted in improvements of state and of agoraphobic anxiety. Except for Trait Anxiety, CO2 was superior on all measures, most clearly on the Fear of Autonomic Sensations. At the 6-month follow-up, 3 patients required further treatment. Except for State Anxiety, the improvements were, on average, maintained. The clinical and theoretical implications are discussed.

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.

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge: Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT2C agonist, and 10 mg ipsapirone, a 5-HT1A agonist, according to double-blind, placebo-controlled, cross-over design. The groups’ levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT1A receptor desensitisation and non-hypothalamic, 5-HT2C receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.