Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine

Bell, Caroline; Forshall, Sam; Adrover, Mariona; Nash, Jon; Hood, Sean; Argyropoulos, Spilios V.; Rich, Ann; Nutt, David

doi:10.1177/026988110201600116

Cited by 83 publications

(80 citation statements)

References 34 publications

(57 reference statements)

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“…Studies so far have shown that treatment with SSRIs significantly decreased the sensitivity of patients with PD to the panicogenic effects of CCK-4, flumazenil, and CO 2 (Bell et al, 2002;Bertani et al, 1997;Perna et al, 1997;Shlik et al, 1997;van Megen et al, 1997). These results support the view that 5-HT-ergic enhancement by SSRIs leads to antipanic effects.…”

Section: Effects Of Treatment On Panic Challengementioning

confidence: 56%

“…These findings are of interest considering that, contrary to SSRIs, tianeptine is believed to increase the 5-HT reuptake. A recent study by the Bristol group found that TD reversed the antipanic effect of chronic treatment with the SSRI paroxetine in PD patients, manifested as an increase in panicogenic response to a flumazenil challenge (Bell et al, 2002). This supports the assumption that SSRIs exert their therapeutic effects in PD by increasing the synaptic availability of 5-HT (Nutt et al, 1999).…”

Section: Effects Of Treatment On Panic Challengementioning

confidence: 72%

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Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

106

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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Section: Effects Of Treatment On Panic Challengementioning

confidence: 56%

Section: Effects Of Treatment On Panic Challengementioning

confidence: 72%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

106

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“…It has been used in studies of panic provocation [Bell et al, 2002;Nutt et al, 1990] and our previous 35% CO 2 studies . The PSI was adapted from Clark and Hemsley [1982] and was administered at baseline for peak effects of inhalation and at the end of each inhalation.…”

Section: Subjective Ratingsmentioning

confidence: 99%

Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers

et al. 2005

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The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety.

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“…For the pathophysiology of panic disorder, the serotonergic system has been considered as performing a role as inferred by challenge studies [41], serotonergic treatment studies [44,45], and brain imaging studies [46]. Since the serotonin transporter regulates serotonergic neurotransmission, 5-HTTLPR has been studied to demonstrate particular associations in research on panic disorder.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic Genes (5-HTT and HTR1A) and Separation Life Events: Gene-by-Environment Interaction for Panic Disorder

et al. 2013

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Background: The polymorphisms of serotonergic genes (5-HTTLPR and HTR1A rs6295) and separation life events have been studied to find an association with panic disorder, respectively. However, there are no studies that have yet evaluated the interaction effect between serotonergic genes and separation life events for panic disorder. Methods: For this study, 194 panic disorder patients and 172 healthy controls were included for genotyping and environmental factor analysis. Separation life events were assessed using the Stressful Life Events Scale and clinical interviews. To evaluate the potential endophenotypes of panic disorder, the Anxiety Sensitivity Index-revised (ASI-R), harm avoidance in the Temperament and Character Inventory (HA), and neuroticism in the Eysenck Personality Questionnaire (neuroticism) scales were administered. Results: For 5-HTTLPR and HTR1A rs6295, there was no significant main effect of each genotype on panic disorder alone. However, the number of separation life events and their interaction with 5-HTTLPR showed a statistically significant effect on panic disorder. In addition, the interaction between 5-HTTLPR and the number of separation life events significantly affected the HA for potential endophenotypes. Conclusion: This study could suggest the effect of the interaction between 5-HTTLPR and separation life events on panic disorder and its potential endophenotype.

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Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine

Cited by 83 publications

References 34 publications

Serotonin Function in Panic Disorder: Important, But Why?

Serotonin Function in Panic Disorder: Important, But Why?

Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers

Serotonergic Genes (5-HTT and HTR1A) and Separation Life Events: Gene-by-Environment Interaction for Panic Disorder

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