Effect of the serotonin transporter gene and of environment on the continuity of anxiety and depression traits throughout adolescence.

Aims. Many studies of various stress reactive phenotypes suggest that 5-HTTLPR short allele carriers (S-carriers) are characterised by the stable trait of negative affectivity that is converted to psychopathology only under conditions of stress. In this study, we examined the moderating role of the 5-HTTLPR on the relationship between two objective chronic risk factors, i.e. socioeconomic status (SES) and family structure, and internalising symptoms across adolescence. Methods. A multigroup path analysis was employed in a general adolescent population sample of a 5-year follow-up study. Results. Internalising problems were significantly more stable in the S-carriers. The focus on the main dimensions of internalising problems, i.e. anxiety and depression, revealed two different developmental patterns. In the S-carriers Anxiety problems seemed to be more stable and to predict a possible evolution towards the development of Depressive problems. In the long allele homozygotes (LL-subjects) the anxiety trait was significantly less stable, and, in late-adolescence, seemed to be significantly predicted by SES, suggesting a possible gene-environment interaction (G × E). Family structure seemed to play a role in a G × E perspective only until early-adolescence, while during late-adolescence SES seemed to play a pivotal role in interaction with 5-HTTLPR, with the S-allele playing a protective role. Conclusions. Future models of the developmental link between environmental adversities and internalising behaviour therefore need to consider that the effect of G × E interaction, may be associated with internalising behaviour via different mechanisms during different time frames and that shifts in the strength of this effect should be expected across development.

Challenging anxiety: a focus on the specificity of respiratory symptoms.

Physiological symptoms are characteristic features of anxiety states. Presumably, specific psychophysiological profiles differentiate between anxiety disorders, which would offer potential for diagnostic purposes. Abundant evidence points to a causal relationship between panic disorder and instability of respiratory regulation. However, the specificity of most measures that indicate aberrant functioning of the respiratory system in PD can be questioned. Possibly, the traditional measures of respiratory functioning are too restricted. The underlying respiratory vulnerability in PD seems to constitute a subtle, unstable trait, which calls for more sensitive and sophisticated measures of respiratory variability and chaos. To increase the probability of finding parameters with diagnostic specificity, the application of disorder specific challenge paradigms is recommended.

Acids in the brain: a factor in panic?

Several methods to experimentally induce panic cause profound acid-base disturbances. Evidence suggests that CO(2) inhalations, lactate infusions and, to a certain extent, voluntary hyperventilation can conceivably lead to a common scenario of brain acidosis in the face of disparate intravascular pH alterations. The importance of this event is reflected in data that support a model in which experimental panic attacks, as proxy to those occurring spontaneously, constitute a response to acute brain acidosis. Given that central CO(2)/H(+) chemoreception is an important drive for ventilation, and many chemosensitive neurons are related to respiration and arousal, this model can explain much of the connection between panic and respiration. We propose that the shared characteristics of CO(2)/H(+) sensing neurons overlap to a point where threatening disturbances in brain pH homeostasis, such as those produced by CO(2) inhalations, elicit a primal emotion that can range from breathlessness to panic.

Desynchrony of fear in phobic exposure.

Intuitively, phobic exposure would seem to be a very stressful experience. However, it is not clear whether the characteristic feature of a classic stress response, activation of the hypothalamic-pituitary-adrenal (HPA) axis, is present in phobic fear. Some instances of phobic fear have been found to be accompanied by robust increases in cortisol, whereas in other instances a dissociation between subjective-behavioural arousal and the HPA-axis has been found. The latter is referred to as desynchrony of fear. The aim of the current study was to test the hypothesis that phobic fear is similar to normal fear and, as such, is accompanied by a robust increase in cortisol values. In all, 16 spider phobic subjects and 16 healthy controls participated in the study. During and following a standardised stepwise exposure paradigm, saliva samples were collected for cortisol determination. In contrast to the controls, the spider phobics reacted with a strong fear reaction to the spiders. However, cortisol levels remained unaffected. The phobic response did not resemble the classic 'fight or flight' response. Some suggest that the HPA-axis response has become extinguished in modern man. Yet, it is possible that phobic fear is not a derivative of an ancient fear but rather a separate entity that relies on other neuroendocrinological systems.

Respiratory patterns in panic disorder reviewed: a focus on biological challenge tests.

OBJECTIVE: To provide a systematic review of studies investigating respiration in PD and comments on relative inconsistencies. METHOD: A Medline search of controlled studies focusing on pCO(2), respiratory rate, tidal volume, and minute volume in PD patients was conducted for baseline/resting condition, challenge, and recovery phase. Respiratory variability and comparisons between panickers and non-panickers were also examined. RESULTS: Lower pCO(2) levels in PD subjects are a consistent finding during the baseline/resting condition, the challenge, and recovery phases. Tidal volume and minute volume are increased in PD subjects relative to controls during the baseline/resting condition. However, the most robust finding is a higher than normal respiratory variability, which appears to be a promising factor for the identification of respiratory etiopathological pathways in PD. CONCLUSION: Respiratory variability might be a candidate for a biological marker of PD: an abnormal breathing pattern as found in panic disorder (PD) patients compared with controls might indicate instability of the respiratory homeostasis.

The effects of opioid receptor blockade on experimental panic provocation with CO2.

Several reports have linked, among other aspects, the role of an opioid system in respiratory physiology with underlying mechanisms of panic attacks. The involvement of the opioid system in experimental panic is to be further probed. This study aimed to determine whether opioid blockade would increase panic-related symptomatology on provocation with 35% CO2 inhaled by healthy volunteers. Participants in a double-blind, randomised crossover design orally received either 50 mg of naltrexone or placebo. Most subjects undertook a double inhalation of 35% CO2 one hour after pre-medication, and a separate group did so after five hours. The reactivity to CO2 and the symptoms elicited by naltrexone alone were measured. Among other findings, naltrexone pre-medication alone elicited significant increments in panic-related symptoms. Responses to CO2 were not significantly different between conditions in either group. These preliminary findings suggest that exposure to opioid blockade alone can potentially elicit symptoms that resemble panic, however, without modifying the response to experimental panic provocation with 35% CO2.

The influence of ethanol infusion on the effects of 35% CO2 challenge. A study in panic disorder patients and healthy volunteers.

UNLABELLED: Alcohol and panic disorders co-occur at a rate that exceeds chance significantly. Early experimental work suggests that alcoholic subjects, compared to non-alcoholics, are less sensitive to sodium lactate and that alcohol intake reduces the response to a 35% CO(2) challenge in Panic Disorder patients. The present study documents the direct pharmacological effect of ethanol infusion on CO(2) induced panic. METHODS: According to a placebo-controlled, double-blind, randomized, cross-over design 10 drug free panic disorder patients and 16 healthy volunteers underwent a 35% CO(2) challenge after intravenous infusion of a moderate dose of ethanol on one test day and of placebo on another test day. RESULTS: Compared to the placebo condition, the effect of the CO(2) challenge was significantly smaller after ethanol infusion (P = 0.041). DISCUSSION: A moderate dose of ethanol decreased the response to a 35% CO(2) without inducing pre challenge sedation. CONCLUSION: The results comfort earlier findings of a direct pharmacological effect of ethanol on panic.

Anxiety sensitivity in children of panic disorder patients.

Anxiety sensitivity (AS), which refers to the tendency to interpret anxiety-related bodily sensations as having potentially harmful somatic, psychological or social consequences, has been proposed as a vulnerability factor for the development of panic disorder (PD). The current study examined the anxiety sensitivity levels in children of parents with panic disorder. Children of panic disorder patients (n = 68) and children of healthy parents (n = 68) filled out the Childhood Anxiety Sensitivity Index, while parents completed the Anxiety Sensitivity Index. Children of parents with panic disorder did not display higher levels of anxiety sensitivity than children of healthy parents. Furthermore, no association between anxiety sensitivity levels of parents with panic disorder and their children was found. Anxiety sensitivity is not clearly manifest in children of parents with panic disorder and might be a developing vulnerability factor that may increase towards late adolescence or early adulthood.

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. METHOD: A selective review of the relevant scientific literature on OCD treatment and treatment resistance was conducted. RESULTS: In addition to serotonin reuptake inhibitors (SRIs) and cognitive-behavioural therapy, alternative monotherapies, SRI augmentation strategies with a variety of drugs and electroconvulsive therapy have shown results in individual cases, but no conclusive evidence has been found in placebo-controlled trials. While studies investigating neurosurgery for refractory OCD show positive results, most of these studies have methodological shortcomings. CONCLUSION: Novel approaches currently under investigation that have shown promising effects for treatment-resistant OCD include SRI augmentation with atypical antipsychotics and chronic deep brain stimulation, a new surgical technique. Placebo-controlled trials for both treatment options will be needed to confirm preliminary findings.

Neuroimmunological parameters in panic disorder.

BACKGROUND: The interaction between immune cells, neurotransmitters and the neuroendocrinological systems plays a role in affective disorders, especially depression. Although panic disorder (PD) shares a lot of features with depression, it is clearly a distinct disorder. Reports on immunological parameters in PD don't provide a clear picture of the immunological status of PD patients. This can partly be attributed to methodological differences between studies and small patient groups. OBJECTIVE: The present study aims to assemble all studies on immunological parameters in PD in order to combine all available data to gain a broader perspective on this matter. METHOD: PubMed was searched for studies describing immunological parameters in PD patients without comorbid disorders or medication use. All studies had to include a healthy control group and the outcome measures had to be shared by at least one other study. RESULTS: Fourteen articles were found. Although the T-lymphocytic branch and the innate immune system were normal, the B-lymphocytic branch showed some differences between PD patients and healthy controls. B-cell counts were increased in PD patients, which was underlined by increased human leucocyte antigen (HLA)-DR counts and increased immunoglobulin A levels. However, B-cell activity following mitogen stimulation was normal. CONCLUSIONS: PD patients show increased B-cell numbers. The finding that B-cell activity is not increased can possibly be attributed to functional exhaustion of these cells. The meaning of this finding remains unclear, although it may be potentially important in affective disorders as the same has been found in depression.

Symptom profiles of natural and laboratory panic attacks.

BACKGROUND: Little accurate information is available about the symptomatology of real-life panic attacks and about how well they are reproduced by an experimental model such as the 35% CO2 challenge. METHOD: Real-life panic symptoms were assessed in a group of 67 panic disorder patients, using daily life monitoring. Panic symptoms elicited by a 35% CO2 challenge were assessed in 61 panic disorder patients, and their frequency was compared with the real-life symptoms. RESULTS: The most frequent real-life symptoms were palpitations, dizziness and trembling. The 35% CO2 challenge reproduced well the majority of real-life symptoms. CONCLUSION: The findings suggest that the 35% CO2 challenge is a marker for spontaneous panic attacks, which are considered the core of panic disorder.

New insights in cognitive behavioural therapy as treatment of panic disorder: a brief overview.

Cognitive behavioural therapy (CBT) has been proved to be very effective in the treatment of panic disorder. In this article we attempt to give a brief representation of more recent insights and techniques in the field of cognitive behavioural therapy in the treatment of panic disorder.

Anxiety sensitivity in first-degree relatives of patients with panic disorder.

Anxiety sensitivity (AS) has been proposed as a risk factor for the development of panic disorder. Strong familial-genetic influences in panic disorder (PD) have been reported. AS may be familial too. The current study therefore examined whether first-degree relatives of PD patients are more anxiety-sensitive than normals. Twenty-three first-degree relatives of PD patients, 38 PD patients and 30 normals were given the Anxiety Sensitive Index and the Body Sensations Questionnaire. It was found that the first-degree relatives were, indeed, more anxiety-sensitive than the normals, but less so than the PD patients, suggesting that AS runs in families.

The effects of acute exercise and high lactate levels on 35% CO2 challenge in healthy volunteers.

OBJECTIVE: To test the possible antipanic effects of acute exercise in healthy volunteers exposed to an inhalation of 35% CO2 challenge. METHOD: Twenty healthy subjects in a randomized separate group design, performed exercise in a bicycle ergometer reaching >6 mm of blood lactate and a control condition of minimal activity in the same fashion with no lactate elevation. Immediately afterwards an inhalation of a vital capacity using a mixture of 35% CO2/65% O2 through a mask was given on both conditions. RESULTS: Subjects under the exercise condition reported less panic symptoms than controls after a CO2 challenge on the diagnostic statistical manual-IV (DSM-IV) Panic Symptom List but no difference on the Visual Analogue Anxiety Scale. CONCLUSION: Subjects under the exertion condition had lactate levels comparable with those of lactate infusions but an inhibitory rather than accumulative effect was seen when combined with a CO2 challenge.

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-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) 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-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.

Panic disorder and idiopathic cardiomyopathy.

OBJECTIVE: This study investigated whether, among a population of cardiac patients, there is a preferential association between idiopathic cardiomyopathy (CMP) and Panic Disorder (PD). METHODS: A total of 93 patients with cardiac failure, 50 of them with CMP, 43 with other cardiac diseases, underwent a standard psychiatric examination using the MINI neuropsychiatric interview. RESULTS: While half of the subjects met the criteria for a psychiatric disorder, PD was no more prevalent in the CMP group compared to other patients. CONCLUSION: This study confirms the high prevalence of psychiatric pathology, particularly anxiety, mood, and alcohol-related disorders, in patients with cardiac failure. However, previous findings on the specific association between CMP and PD could not be replicated.

Effects of low-dose cholecystokinin on respiratory function in healthy volunteers.

Injection of high doses of cholecystokinin tetrapeptide (CCK-4), a recent experimental model for panic, causes panic attacks and respiratory stimulation, a key feature of panic, in healthy volunteers. However, it has not yet been established whether respiratory stimulation is specifically linked to panic or merely an effect of arousal in general. Results of the present study show that respiratory stimulation is not merely linked to higher arousal and suggest a link between CCK-provoked panic and respiratory stimulation.