Lactate infusions and panic attacks: Do patients and controls respond differently? (2023)

Prospective research indicates sleep deprivation potentiates anxiety development, yet relatively little research has examined the effects of sleep deprivation in terms of specific types of anxiety. The current study tested the association between acute sleep deprivation and panic-relevant biological challenge responding among nonclinical participants. One hundred and two participants were randomly assigned to either an experimental (acute sleep deprivation) or control (no sleep deprivation) group. The day prior to and following the experimental (sleep) manipulation, participants completed a 5-minute 10% carbon dioxide–enriched air laboratory-based biological challenge. As predicted, sleep deprivation increased anxious and fearful responding to the challenge. Findings suggest sleep deprivation may be an important factor to consider in models of panic development. There are several areas in this general domain that warrant additional investigation.

The main paradigm of experimental psychiatry is the carefully controlled time-limited production of a pathological picture in volunteering subjects under safe laboratory conditions. Most often, such a procedure relies on either the manipulation of a physiological parameter or administration of a pharmacological agent in order to unveil underlying vulnerabilities believed to be directly related to the pathogenesis of the disorder. Because they intentionally put the organism under strain, such procedures have been referred to as “challenges”. The interest of an experimental model mimicking a clinical condition lies in its validity. Insights in the underlying pathophysiology will progress to the extent that a particular challenge can be linked to a syndrome in particular individuals, who are also prone to the development of the same syndrome in real-life environment. In other words, experimental models are supposed to act as biological markers of clinical disorders. Human models of panic and fear are scrutinized under different aspects for their validation. These aspects include safety, convergence, discrimination, reliability, and clinical validity. However, these aspects of validation can become blurred without a clear agreement on what is called anxiety, fear, or panic, and their correspondence with spontaneous panic attack and situational panic attacks. In this scope, animal models that have mapped fear and anxiety in two different defense systems may contribute to clarify this issue. Ultimately, the identification of a reliable biomarker can pave the way for studies into the genetic determinants of susceptibility to fear and panic and new therapeutic approaches.

The authors provide an overview of the current state of knowledge with regards to the neurobiological mechanisms involved in normal and pathological anxiety. A brief review of the classification and cognitive psychology of anxiety is followed by a more in-depth look at the neuroanatomical and neurochemical processes and their relevance to our understanding of the modes of action of anxiolytic drugs. The serotonergic, noradrenergic, and γ-aminobutyric acidergic systems are reviewed. The numerous physiological and pharmacological methods of anxiety provocation and the increasing importance of functional neuroimaging are also examined. The review provides an overview of the biology and basic pharmacology of anxiolytic drugs, and compliments the more clinically oriented companion review.

This study compares the hemodynamic response to panic disorder subjects with that of normal controls during respiratory challenges. Panic patients meeting DSM-IIIR criteria for panic disorder and normal controls were challenged with room air hyperventilation, 5% CO₂ breathing, and 7% CO₂ breathing, Measurements of pulse and blood pressure were taken at resting baseline and before and at the end of each respiratory challenge. Panic attack to each challenge was determined by using raters blinded to subject diagnosis and each subject's self-rating of panic. Significantly larger systolic and diastolic blood pressure increases were found in patients who panicked with room air hyperventilation than nonpanicking patients or normal controls. No significant blood pressure differences were found with 7% or 5% CO₂ challenges, but higher pulse rates were found in the patient group. It may be possible that panic with room air hyperventilation causes a significant increase in systolic and diastolic blood pressure, or that a subgroup of panic disorder patients has a hyperactive vascular response to hypocapnia. These patients panic with room air hyperventilation and develop greater vasoconstriction and/or increased blood pressure response.

This article examines the effect of baseline anxiety, anxiety sensitivity and dysfunctional attitudes on the response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. CCK-4 and placebo were administered to 14 subjects in a double-blind manner. Four volunteers experienced a panic attack after CCK-4 administration. Those subjects who panicked had significantly higher baseline scores on dysfunctional attitudes. Dysfunctional thought patterns appeared also to predict number of symptoms and experience of cognitive and affective symptoms during injection. Baseline anxiety as well as anxiety sensitivity predicted reactions to placebo but not panic responses to CCK-4. Results suggest that a general tendency towards erroneous interpretation of information has some role in mediating the panicogenic effects of CCK-4, and also interpersonal sensitivity may constitute a vulnerability factor for panic. Psychological factors that have been considered more specific to panic disorder, namely high state and trait anxiety as well as anxiety sensitivity, appeared mainly to determine general reactions to a threatening situation.

The Hyperventilation Provocation Test (HVPT) has become a routine procedure in the diagnosis of hyperventilation syndrome (HVS). During an HVPT the patient voluntarily overbreathes for several minutes to produce hypocapnia. The test is considered positive if the induced symptoms are recognized by the patient as similar to those experienced in daily life. The present study tests the assumption that hypocapnia is the primary trigger for symptoms during an HVPT. In a randomized double-blind crossover design, 115 patients suspected of HVS and 40 healthy controls performed an HVPT and a placebo test (PT, isocapnic overbreathing). The HVPT induced more symptoms than the PT, especially more neuromuscular symptoms, cerebral symptoms, paresthesias, and temperature sensations. However, the absolute difference between the number of symptoms induced by the HVPT and PT was small. In patients, the PT induced 66% of symptoms induced by the HVPT. In the control group this percentage was 60%. The low specificity of the HVPT implies that symptom recognition during the HVPT is invalid as a diagnostic criterion for HVS.

Psychiatry Research, Volume 220, Issues 1–2, 2014, pp. 37-43

A common T/C polymorphism within the ninth intron of the KIBRA gene (rs17070145) is thought to influence memory in humans. Since cognitive impairment, including memory, is a core feature of schizophrenia, we attempted to investigate this association in an independent sample of adolescent patients with early-onset schizophrenia (EOS; onset before age 18) probands and their healthy siblings. In a sample of 25 pairs of EOS proband-healthy full sibling, we sought to investigate the association of KIBRA with memory performance. Episodic memory was measured using immediate and delayed recall measures of the California Verbal Learning Test. EOS underperformed at immediate and delayed recall compared with siblings. In a combined analysis (TT vs. TC/CC) assuming a C dominant model of inheritance, we found a main effect of genotype where individuals with TT genotype outperformed non-TT-carriers at immediate and delayed recall. A genotype by group interaction showed that EOS with TT genotype did not show a memory advantage over siblings with TT or non-TT-carriers at immediate or delayed recall. Siblings with TT genotype showed enhanced immediate recall (not delayed recall) compared with non-TT-carriers. This study demonstrates an association between the KIBRA gene and episodic memory (immediate free recall) and suggests a differential effect of this genetic variant in EOS and healthy siblings.

Enzyme and Microbial Technology, Volumes 58–59, 2014, pp. 14-21

The mass distribution regularity in substrate of solid-state fermentation (SSF) has rarely been reported due to the heterogeneity of solid medium and the lack of suitable instrument and method, which limited the comprehensive analysis and enhancement of the SSF performance. In this work, the distributions of water, biomass, and fermentation product in different medium depths of SSF were determined using near-infrared spectroscopy (NIRS) and the developed models. Based on the mass distribution regularity, the effects of gas double-dynamic on heat transfer, microbial growth and metabolism, and product distribution gradient were systematically investigated. Results indicated that the maximum temperature of substrate and the maximum carbon dioxide evolution rate (CER) were 39.5°C and 2.48mg/(hg) under static aeration solid-state fermentation (SASSF) and 33.9°C and 5.38mg/(hg) under gas double-dynamic solid-state fermentation (GDSSF), respectively, with the environmental temperature for fermentation of 30±1°C. The fermentation production (cellulase activity) ratios of the upper, middle, and lower levels were 1:0.90:0.78 at seventh day under SASSF and 1:0.95:0.89 at fifth day under GDSSF. Therefore, combined with NIRS analysis, gas double-dynamic could effectively strengthen the solid-state fermentation performance due to the enhancement of heat transfer, the stimulation of microbial metabolism and the increase of the homogeneity of fermentation products.

Early Human Development, Volume 93, 2016, pp. 57-61

Chest, Volume 154, Issue 3, 2018, pp. 512-520

Journal of Obsessive-Compulsive and Related Disorders, Volume 7, 2015, pp. 29-34

This study examined whether patients with obsessive–compulsive disorder (OCD) have deficits in executive functioning and memory, as well as the specificity of any OCD-related neuropsychological dysfunction. Previous studies have indicated poorer performance among individuals with OCD compared to healthy controls across the majority of neuropsychological domains, however, findings are very inconsistent. We included 34 individuals with bipolar-I disorder (BP-I), 35 untreated patients with OCD, and 33 healthy controls matched for age, gender, and education. Participants completed the Rey Auditory Verbal Learning Test (RAVLT), the Wechsler Memory Scale-Revised (WMS-R) visual-reproduction subscale, and Stroop Color-Word Interference Test (SCWIT). Compared to both healthy controls and participants with OCD, patients with BP-I showed poorer performance in long-delay verbal recall. Although participants with OCD performed more poorly in visual recall than both BP-I patients and healthy controls, their scores were within the normative range. In pairwise comparisons, OCD did not differ from either BP-I or controls. No significant differences were found in verbal memory or Stroop performance between OCD and healthy controls. Overall, we found no significant differences in neuropsychological performance between patients with OCD and healthy controls that could potentially contribute to functional impairment.

Comprehensive Psychiatry, Volume 69, 2016, pp. 193-201