Increased cannabis intake during the COVID-19 pandemic is associated with worsening of depression symptoms in people with PTSD.

BACKGROUND: Some evidence suggests substance use affects clinical outcomes in people with posttraumatic stress disorder (PTSD). However, more work is required to examine links between mental health and cannabis use in PTSD during exposure to external stressors such as the COVID-19 pandemic. This study assessed mental health factors in individuals with self-reported PTSD to: (a) determine whether stress, anxiety, and depression symptoms were associated with changes in cannabis consumption across the pandemic, and (b) to contrast the degree to which clinically significant perceived symptom worsening was associated with changes in cannabis intake. METHOD: Data were obtained as part of a larger web-based population survey from April 3rd to June 24th 2020 (i.e., first wave of the pandemic in Canada). Participants (N = 462) with self-reported PTSD completed questionnaires to assess mental health symptoms and answered questions pertaining to their cannabis intake. Participants were categorized according to whether they were using cannabis or not, and if using, whether their use frequency increased, decreased, or remained unchanged during the pandemic. RESULTS: Findings indicated an overall perceived worsening of stress, anxiety, and depression symptoms across all groups. A higher-than-expected proportion of individuals who increased their cannabis consumption reached threshold for minimal clinically important worsening of depression, X2(3) = 10.795, p = 0.013 (Cramer's V = 0.166). CONCLUSION: Overall, those who increased cannabis use during the pandemic were more prone to undergo meaningful perceived worsening of depression symptoms. Prospective investigations will be critical next steps to determine the directionality of the relationship between cannabis and depressive symptoms.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

Advances in molecular genetics of panic disorder.

The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. Although the data from twin and family studies suggest an involvement of genetic factors in the familial transmission of PD with the heritability estimate near 40%, the genetic substrate underlying panicogenesis is not yet understood. The linkage studies so far have suggested that chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 are associated with the transmission of PD phenotypes. To date, more than 350 candidate genes have been examined in association studies of PD, but most of these results remain inconsistent, negative, or not clearly replicated. Only Val158Met polymorphism of the catechol-O-methyltransferase gene has been implicated in susceptibility to PD by several studies in independent samples and confirmed in a recent meta-analysis. However, the specific role of this genetic variation in PD requires additional analysis considering its gender- and ethnicity-dependent effect and putative impact on cognitive functions. The recent advantages in bioinformatics and genotyping technologies, including genome-wide association and gene expression methods, provide the means for far more comprehensive discovery in PD. The progress in clinical and neurobiological concepts of PD may further guide genetic research through the current controversies to more definitive findings.

Effects of bupropion augmentation on pro-inflammatory cytokines in escitalopram-resistant patients with major depressive disorder.

Studies so far have provided contradictory results on immune system markers during use of antidepressants. There are no data on changes in immune parameters after treatment augmentation. The present study aimed to clarify whether the addition of bupropion in escitalopram-resistant patients with major depression causes changes in the immune system and whether treatment response could be predicted by baseline levels of cytokines. We recruited 28 depressive patients (11 men and 17 women) who did not respond to 12-week treatment with escitalopram (20 mg/d) for an augmentation trial with bupropion (150-300 mg/day). The levels of soluble interleukin-2 receptor, interleukin-8 (IL-8) and tumor-necrosis factor-alpha were measured before and 6 weeks after addition of bupropion. For a control group, we recruited 45 healthy volunteers (19 men and 26 women). The results indicated that the baseline levels of studied cytokines did not predict treatment response to bupropion augmentation. Concentration of IL-8 increased during the treatment similarly in both responder and non-responder groups. Although bupropion augmentation had increased the response rate in escitalopram-resistant patients, this clinical improvement was not accompanied by specific changes in studied cytokine levels.

CCK-4-induced anxiety but not panic is associated with serum brain-derived neurotrophic factor in healthy subjects.

Recent animal studies consistently confirm the involvement of brain-derived neurotrophic factor (BDNF) in the regulation of anxiety-related behaviours. The role of BDNF in human anxiety has been less investigated. The aim of our study was to examine the association between serum BDNF levels and panic/anxiety responses to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. BDNF concentrations were detected in serum samples of 37 male and female volunteers before and 120 min after CCK-4 injection. The baseline levels of serum BDNF did not predict the occurrence of CCK-4-induced panic attacks or intensity of panic symptoms and did not significantly change 2 h after the challenge. BDNF serum concentrations 120 min after provocation did not differentiate panickers from non-panickers; however, the subjects reporting stronger anxiety response showed higher levels of BDNF than those with mild anxiety. The anxiety net increase on the Visual Analogue Scale, but not severity of panic symptoms, significantly and positively correlated with the change in BDNF concentration from baseline values. This is the first challenge study to demonstrate a possible impact of BDNF on human anxiety. Our findings suggest a general involvement of BDNF in the regulation of anxiety rather than a specific role of BDNF in disposition to panic attacks.

Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a comparison of two time points.

BACKGROUND: Several functional imaging studies have demonstrated increases of brain activity in the temporofrontal, cingulate, and claustrum regions during a pharmacologically induced panic attack when scanning was done at a single point in time. However, no study has evaluated changes in brain activity at two time points during a panic attack. We hypothesized that in response to a single bolus injection of the panicogen cholecystokinin-4 (CCK-4) in healthy volunteers, changes in regional cerebral blood flow (rCBF) might be different if scanning were done at two different time points. METHODS: To test this hypothesis, we conducted a single-blind study, using positron emission tomography (PET). To determine the time effect of panic attack on brain activity, we performed either early scan or late scan covering the first or the second minute after CCK-4 bolus injection, respectively. The PET images were analyzed by statistical parametric mapping (SPM) followed by region of interest (ROI) analysis. RESULTS: The results showed significant differences between the early and the late scan. The early effects of CCK-4 are accompanied by increases in rCBF in the hypothalamic region, whereas the late scan showed an increase in rCBF in the claustrum-insular region. Reductions in rCBF were observed for both time groups in the medial frontal region. A separate scan for anticipatory anxiety demonstrated rCBF increases in the anterior cingulate region and decreases in the occipital regions. CONCLUSIONS: These results may support the hypothesis that changes in rCBF as a function of time during CCK-4-induced panic might correspond to a neurocircuitry involved in panic attacks.

The effect of cholecystokinin tetrapeptide on respiratory resistance in healthy volunteers.

The effects of cholecystokinin tetrapeptide (CCK-4) on respiratory resistance were studied in 14 healthy volunteers by the registration of slow vital capacity and flow volume loop during forced respiration test. The administration of CCK-4 (50 micrograms) was performed in a double-blind and placebo-controlled design. Injections of CCK-4 induced prominent and time-limited paniclike symptoms in all healthy volunteers. Four volunteers (29%) experienced a panic attack. Subjective dyspnea was experienced by the majority of subjects at the peak of CCK-4 effect and seemed related to a diminution in vital capacity parameters; however, the forced respiration test did not reveal bronchoconstriction after CCK-4 challenge. Administration of CCK-4 also induced a short-lasting increase in heart rate and skin blood flow. This study suggests that dyspnea induced by CCK-4 is not related to changes in respiratory resistance.

The ventilatory response to cholecystokinin tetrapeptide in healthy volunteers.

The cholecystokinin (CCK) system, which has been shown to interact with both the panicogenic and respiratory systems, provides an interesting mechanism to further evaluate the central chemoreceptor and its effect on panic attack sensitivity. Intravenous CCK, a naturally occurring neuropeptide in the brain, has been found to induce the emotional and somatic symptoms of panic in both Panic Disorder (PD) and Normal Control (NC) subjects in a dose-dependent and reproducible fashion. To induce these effects, lower doses of intravenous CCK are required in the PD patients, relative to the NC subjects potentially suggesting that endogenous alterations in the CCK system may be contributing to the development of PD. Intravenous administration of CCK-4 in association with panic also results in subjective dyspnea, that is, diminution in vital capacity without an effect on the respiratory resistance. CCK-4 also causes a significant increase in tidal volume and minute ventilation but has no effect on breathing frequency. These observations suggest that a CCK-B receptor agonist may be acting as a respiratory stimulant, exerting its effect on anxiety through a direct effect on respiration. This study represents an examination of the specific effects of CCK-4 on the central chemoreceptor response. The study used a modified rebreathing technique, which accurately measures the ventilatory response to carbon dioxide in terms of both threshold and sensitivity. This technique requires the subject to rebreathe from a bag containing a hyperoxic and hypercapnic gas mixture resulting in rapid equilibration between alveolar gas and arterial blood. Use of a hyperoxic gas allows for the preferential examination of the central chemoreflexes (sensitive to CO(2)) with little if any effect of the peripheral (oxygen sensitive) chemoreflexes. After significant training, 15 healthy control subjects were assigned via a double blind procedure to receive an intravenous injection of placebo or CCK-4, using a between-subjects design. A between-subjects comparison was undertaken for the injection run (run #3) between subjects receiving the CCK-4 injection and those receiving the placebo injection. As well, a within-subject comparison was undertaken to compare the results of the run following the injection (run #3) vs. the previous run when no injection took place (run #2). No significant differences were noted between subjects who received CCK-4 as compared with placebo for: basal or sub-threshold ventilation, threshold CO(2) resulting in a change in ventilation, or sensitivity of the central chemoreflex, regardless of whether a panic attack did or did not take place. In addition, within the group receiving the CCK-4 challenge, no significant differences were noted during run #3 (received the CCK-4 injection) and a prior run where no injection took place (run #2). We conclude that CCK-4 does not act to induce panic by altering the central (CO(2) sensitive) chemoreceptor.

Cholecystokinin and psychiatric disorders : role in aetiology and potential of receptor antagonists in therapy.

Cholecystokinin (CCK) is one of the most abundant neuropeptides in the brain. It is found in the highest levels in cortical and limbic structures and also in the basal ganglia. Two subtypes of CCK receptors have been described in the brain and gastrointestinal tissues. CCK(A) (alimentary subtype) receptors are mainly located in the gastrointestinal tract, regulating secretion of enzymes from the pancreas and emptying of the gallbladder. However, CCK(A) receptors are also found in several brain regions, with the highest densities in structures poorly protected by the haematoencephalic barrier (the area postrema, nucleus tractus solitarius and hypothalamus). The distribution of CCK(B) (brain subtype) receptors overlaps with the localisation of CCK and its mRNA in different brain areas, with the highest densities in the cerebral cortex, basal ganglia, nucleus accumbens and forebrain limbic structures.Both subtype of CCK receptor belong to the guanine nucleotide-binding protein-(G protein)-linked receptor superfamily containing 7 transmembrane domains. Signal transduction at CCK receptors is mediated via G(q) protein-related activation of phospholipase C and the formation of inositol 1,4,5-triphosphate (IP(3)) and 1,2-diacylglycerol (DAG). Recent cloning of CCK(A) and CCK(B) receptors has shown that mRNA for both receptors is distributed in the same tissues as established in radioligand binding and receptor autoradiography studies, with few exceptions.The existence of multiple CCK receptors has fuelled the development of selective CCK(A) and CCK(B) receptor antagonists. These antagonists belong to distinct chemical groups, including dibutyryl derivatives of cyclic nucleotides, amino acid derivatives, partial sequences and derivatives of the -COOH terminal sequence heptapeptides of CCK, benzodiazepine derivatives, 'peptoids' based on fragments of the CCK molecule, and pyrazolidinones. At the present time, the compounds of choice for blockade of the CCK(A) receptor are lorglumide, devazepide and lintitript (SR27897). L-365,260, CI-988, L-740,093 and LY288513 are the drugs most widely used to block CCK(B) receptors.Studies with CCK antagonists (and agonists) in animals and humans suggest a role for CCK in the regulation of anxiety and panic. The administration of CCK agonists [ceruletide (caerulein), CCK-4, pentagastrin] has an anxiogenic action in various animal models and in different animal species. However, the anxiogenic action of CCK agonists is restricted to nonconditioned (ethological) models of anxiety, with very limited activity in the 'classical' conditioned models. Pharmacological studies have revealed that CCK(B) receptors are the key targets in the anxiogenic action of CCK agonists. Nevertheless, CCK(B) antagonists displayed very little activity, if any at all, in these models, but strongly antagonised the effects of CCK(B) agonists. The anxiogenic/panicogenic action of CCK(B) agonists (CCK-4, pentagastrin) is even more pronounced in human studies, but the effectiveness of CCK(B) antagonists as anxiolytics remains unclear. Clinical trials performed to date have provided inconclusive data about the anxiolytic potential of CCK(B) receptor antagonists, probably because of limiting pharmacokinetic factors.The results of some animal experiments suggest a role for CCK in depression. The administration of CCK(B) antagonists causes antidepressant-like action in mouse models of depression. However, human studies replicating this result have yet to be carried out.A prominent biochemical alteration in schizophrenia is a reduction of CCK levels in the cerebral cortex. This change may be related to the loss of cortical neurons, due to the schizophrenic process itself. In animal studies (mainly in mice), administration of CCK agonists and antagonists has been shown to be effective in several models, reflecting a possible antipsychotic activity of these drugs. However, the data obtained in human studies suggest that CCK agonists and antagonists do not improve the symptoms of schizophrenia. Taking into account the reduced levels of CCK and its receptors found in schizophrenia, treatments increasing, but not blocking, brain CCK activity may be more appropriate.

Decrease in short-term memory function induced by CCK-4 in healthy volunteers.

The purpose of this study was to assess the effects of continuous intravenous infusion of the central cholecystokinin (CCK) receptor agonist, CCK-4, on short-term memory and psychomotor performance in healthy volunteers in a double-blind, placebo-controlled, parallel group study. Compared to placebo, CCK-4 (0.5 mg/h) significantly impaired performance on free-recall and recognition of words in the middle of the CCK-4 infusion, but did not affect psychomotor acuity. The results of this study indicate that CCK-4 may exert a negative influence on memory consolidation and retrieval.

Effects of CCK-4 infusion on the acoustic eye-blink startle and psychophysiological measures in healthy volunteers.

The acoustic startle response (ASR) and a range of psychophysiological parameters were evaluated during a continuous intravenous administration of cholecystokinin-tetrapeptide (CCK-4) in healthy volunteers. Subjects (n=28) were randomly assigned to double-blind infusion of either CCK-4 (0.5 mg/60 min) or placebo. The ASR sessions were performed prior to infusion and at 20 min and 50 min after the onset of infusion by recording eye-blink response to a series of acoustic stimuli (110 dB, 40 ms). An effect of CCK-4 on the eye-blink startle was observed in the first half of infusion. CCK-4 produced an increase of eye-blink startle amplitude from baseline values in contrast to the decrease observed at this time point with placebo. A mild increase in anxiety and heart rate followed by fatigue was reported with CCK-4. Administration of CCK-4 produced increases in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and growth hormone. The results of this study show that a prolonged intravenous administration of CCK-4 may be a useful challenge method for further studies on the role of CCK system in the modulation of human anxiety and stress response.

Emotional and cognitive factors connected with response to cholecystokinin tetrapeptide in healthy volunteers.

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.

Associations between LSAMP gene polymorphisms and major depressive disorder and panic disorder.

The purpose of this case-control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans.

Course of depression: findings from cross-sectional survey in rural Udmurtia.

The aim of this study was to investigate the course of depression and to find the predictors of its chronicity and recurrence in the rural population of Udmurtia. In the sample of 232 respondents identified as having cases of unipolar depression, 21.1% had single episodes, 62.5% had recurrent episodes, and a chronic course was evident in 16.4%. Two demographic factors, Udmurt ethnicity and unmarried marital status, were significantly associated with both recurrent and chronic course of depression. A history of suicide attempt was associated only with recurrent depression; however, a trend towards a higher rate of suicide attempts was also found in the chronic depression subgroup. Factors associated only with chronic depression were poor family relationships and comorbidity with dysthymia.

Prevalence of ICD-10 harmful use of alcohol and alcohol dependence among the rural population in Udmurtia.

A sample of 855 rural adult inhabitants in Udmurtia was interviewed by the Composite International Diagnostic Interview 1:1 (CIDI) to investigate the incidence and prevalence of alcohol-related disorders. Harmful use of alcohol and alcohol dependence affected 37.1% of the population according to ICD-10 and DSM-III-R in a lifetime period. The incidence of alcohol dependence in the previous year was 0.8% (1.4% in men, 0.4% in women). Alcohol-related disorders were more common in men (72.6%) than in women (10.3%). Correlates of alcohol dependence were sex (69.3% in men, 3.7% in women), lower education (40.1%) and being divorced in men (77.8%). Alcohol dependence had a high comorbidity with social phobia in Udmurt men and with depression in Russian men.

A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects.

Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin (CCK) receptors. This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety. This double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity, enhances elevated-plus maze performance, and attenuates the acoustic startle response (ASR). In this study, the authors evaluated the effects of Gotu Kola on the ASR in humans. Subjects were randomly assigned to receive either a single 12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The results revealed that compared with placebo, Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no significant effect on self-rated mood, heart rate, or blood pressure. These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR. It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes.

Cholecystokinin-induced anxiety in rats: relevance of pre-experimental stress and seasonal variations.

OBJECTIVE: To examine the influence of pre-experimental stress on the anxiogenic-like action of caerulein, an agonist of cholecystokinin (CCK) receptors. Differences in the anxiety levels of rats in summer and winter, and the role of CCK in these behavioural alterations, were also examined. DESIGN: Prospective animal study. INTERVENTIONS: Male Wistar rats were injected with the CCK agonist caerulein, or the CCK antagonists L-365,260 or devazepide, after being exposed to pre-experimental stress (handling and isolation). OUTCOME MEASURES: Performance in the plus-maze model of anxiety; serum levels of prolactin, thyrotropin and growth hormone; brain density and affinity of dopamine D2, serotonin 5-HT2 and CCK receptors. RESULTS: Caerulein (5 micrograms/kg, subcutaneous injection) caused the strongest action in animals brought to the experimental room immediately before the experiment and kept in isolation after the administration of caerulein. Caerulein did not cause any reduction of exploratory activity in rats made familiar with the experimental room and kept in the home-cage after the injection of the CCK agonist. The anti-exploratory action of caerulein in stressed rats was reversed by the CCK antagonist L-365,260 (100 micrograms/kg, intraperitoneal injection), demonstrating the involvement of the CCKB receptor subtype. In addition, seasonal fluctuations occur in the exploratory activity of rats; such activity was much lower in July than in November. The rats displaying the reduced exploratory activity had an increased number of CCK receptors in the frontal cortex and hippocampus. Simultaneously, the density of serotonin 5-HT2 receptors in the frontal cortex, but not that of dopamine D2 receptors in the striatum, was elevated. The blood level of growth hormone was also higher in July. CONCLUSIONS: The anti-exploratory action of caerulein appears to be dependent on the pre-experimental stress of rats. Moreover, the seasonal variations of exploratory behaviour of rats are evident in the plus-maze model of anxiety. The reduced exploratory activity in summer appears to be related to the elevated density of CCK and 5-HT2 receptors in the brain.

Effects of citalopram treatment on behavioural, cardiovascular and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder.

Eight patients with panic disorder were administered 20 micrograms of cholecystokinin tetrapeptide (CCK-4) before and after 8 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. All patients responded to treatment by showing a significant general improvement and reaching a panic-free state for 2 weeks. At the rechallenge with CCK-4, patients displayed a marked reduction in the intensity and number of panic symptoms. The frequency of panic attacks induced with CCK-4 decreased by 50% after treatment. Citalopram treatment had no substantial effect on cardiovascular (heart rate and blood pressure) or hormonal (cortisol, prolactin and growth hormone) responses to CCK-4. Patients who still had panic attacks after treatment demonstrated a blunted growth hormone response to CCK-4 that was not seen in those who did not have panic attacks. This study suggests that treatment with an SSRI can reduce an enhanced sensitivity to CCK-4 without modifying cardiovascular and neuroendocrine responses to CCK-4 in patients with panic disorder.

Acute effects of cholecystokinin tetrapeptide on brain stem auditory evoked potentials in healthy volunteers.

This study investigated the effects of continuous slow intravenous infusion of cholecystokinin tetrapeptide (CCK-4) on brain stem auditory evoked potentials (BSAEP) in healthy subjects. Twenty-four subjects, 15 females and 9 males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. BSAEPs, mood, physical symptoms, and vital signs were assessed once before infusion and at 10 min and 40 min after the onset of infusion. In the 16 subjects (N = 8, CCK-4; N = 8, placebo) CCK-4, compared to placebo, delayed peak I latency during early infusion, slowed the latencies of peaks III and V, and decreased the amplitude of peak III throughout the infusion. No significant treatment differences were observed with respect to symptoms, mood, or cardiovascular measures. These preliminary findings suggest that CCK-4 may interfere with information processing in the brain stem auditory pathways and that prolonged intravenous CCK-4 administration may be a useful challenge paradigm for investigating CCK's modulatory role on brain stem mechanisms mediating anxiety and panic in humans.

Prevalence of mood disorders in the rural population of Udmurtia.

A sample of 855 rural adult inhabitants of Udmurtia was interviewed by means of the Composite International Diagnostic Interview (CIDI) in order to investigate the incidence and prevalence of mood disorders. Depression affected 30.5% of the population according to ICD-10, and 22% according to DSM-III-R over a 12-month period. Depressive disorders were more common in women (40.5%) than in men (17.4%), and in subjects who were widowed (68.8%), divorced (55.6%) or had poor family relationships. Depression was not related to ethnicity, educational level, income or living conditions. Depression showed a high level of comorbidity with social phobia in Udmurts and with persistent somatoform pain disorder in Russian women. The annual incidence of depressive episode was 7.5%, and the highest risk of depression was among younger women and older men.