Temporal stability and coherence of anxiety, dyspnea, and physiological variables in panic disorder

Twenty-five panic disorder (PD) patients, 19 social phobics (SP), and 20 healthy controls (HC) sat quietly for 15 min, rating their anxiety and dyspnea every 30 s while respiratory, cardiovascular, and electrodermal responses were recorded. No panic attacks were reported. For self-reported anxiety and dyspnea, within-subject variability over time was higher in PD than in SP or HC. In PD within-subject correlations across 30-s epochs were significant for (a) self-reported anxiety versus dyspnea, end-tidal pCO₂, minute volume, duty cycle, skin conductance level, and interbeat interval, and for (b) dyspnea versus end-tidal pCO₂, minute volume, tidal volume, and inspiratory flow rate. Several positive or negative correlations were greater in PD than in other groups. Thus in PD, experienced anxiety and dyspnea are temporally unstable but are correlated with each other and with fluctuations in respiratory and autonomic variables, even in the absence of panic attacks.     

Differential cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations

The potential differences in cerebrovascular responses between the anterior and posterior circulations to changes in CO₂ are unclear in humans. Using transcranial Doppler ultrasound, we compared the CO₂ reactivity of the (1) BA and PCA and (2) MCA and PCA during hyperoxic rebreathing in supine position. The reactivity in the BA and PCA was similar in both absolute (1.27 ± 0.5 and 1.27 ± 0.6 cm/s/Torr; P = 0.992) and relative (3.98 ± 1.3 and 3.66 ± 1.5%/Torr CO₂; P = 0.581) measures, suggesting that the PCA is an adequate surrogate measure of reactivity for the BA. The MCA reactivity was greater than the PCA in absolute (2.09 ± 0.7 and 1.22 ± 0.5 cm/s/Torr CO₂; P < 0.001), but not relative measures (3.25 ± 1.0 and 3.56 ± 1.6%/Torr CO₂; P = 0.629). Our findings (a) confirm regional differences in the absolute reactivity in the human brain and (b) suggest that in cerebrovascular studies investigating functions mediated by posterior brain structures (e.g., control of breathing), the posterior vasculature should also be insonated.     

Novel method for transdiaphragmatic pressure measurements in mice

The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n = 8) and C57BL/6 × 129 (n = 9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O₂)–hypercapnia (5% CO₂), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p = 0.001). No difference in Pdi across behaviors was evident between mouse strains (p = 0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.     

Heart rate and autonomic response to stress after experimental induction of worry versus relaxation in healthy,high-worry,and generalized anxiety disorder individuals

Generalized anxiety disorder (GAD) is the most commonly occurring anxiety disorder and has been related to cardiovascular morbidity such as cardiac ischemia, sudden cardiac death, and myocardial infarction. Both GAD and its cardinal symptom – worry – have been shown to promote muted physiological reactivity in response to laboratory and ecological stressors. Importantly, no study to date has examined the concurrent and relative contributions of trait and state worry within healthy controls, (non-clinical) high trait-worry controls, and GAD participants. The present study examined heart rate (HR), respiratory sinus arrhythmia (RSA), and salivary alpha-amylase (sAA) responses to laboratory stress during and following the experimental induction of worry versus relaxation in healthy controls (n = 42), high trait worriers (n = 33) and participants with GAD (n = 76). All groups exhibited increased HR and decreased RSA in response to the stressor, with no differences by condition. Baseline sAA significantly moderated HR and RSA reactivity, such that higher sAA predicted greater increases in HR and decreases in RSA. There was a significant group by baseline sAA interaction such that in GAD, higher baseline sAA predicted decreased change in sAA during stress, whereas higher baseline sAA predicted greater sAA change in healthy controls. High-worry controls fell non-significantly between these groups. The present study provides additional evidence for the effect of worry on diminished HR stress response and points to possible suppression of adrenergic sympathetic stress responses in GAD.     

Shared genetic contributions to anxiety disorders and pathological gambling in a male population

Background

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known.

Method

Data from the Vietnam Era Twin Registry (n = 7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD).

Results

While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r_A = 0.53). In contrast, substantial correlations were observed between both the genetic (r_A = 0.34) and unique environmental (r_E = 0.31) contributions to PG and PD.

Limitations

Results may be limited to middle aged males.

Conclusions

The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences.     

What goes up can come down? A preliminary investigation of emotion reactivity and emotion recovery in bipolar disorder

Background

How is emotion disrupted in bipolar disorder? Two studies are presented that adopt a multi-method approach to investigate emotion reactivity and emotion recovery in bipolar I disorder.

Methods

Across both studies, individuals with inter-episode bipolar disorder and healthy controls were shown three emotion-eliciting films (neutral, happy, and sad) and experiential and physiological responses were measured. In Study 1, bipolar (BD; n = 23) and non-clinical control (NC; n = 24) participants' emotional reactivity during film clips was assessed. In Study 2, a separate sample of BD (n = 23) and NC (n = 25) participants' emotion recovery was assessed after the film clips were assessed.

Results

Results indicated that the BD group exhibited increased self-reported positive emotion and respiratory sinus arrhythmia across all films compared to the NC group. There were no group differences in emotion recovery.

Discussion

Taken together, these results suggest that bipolar disorder is associated with increased positive emotion reactivity, but not emotion recovery, across contexts.     

The role of childhood abuse in HPA-axis reactivity in Social Anxiety Disorder: A pilot study

Background

Studies on depression have found that childhood abuse (CA) is associated with a persistent sensitization of the hypothalamic-pituitary-adrenal (HPA)-axis to stress in adulthood. So far, it is unknown whether this HPA-axis sensitization is specific to depression, or whether this is a more general outcome associated with CA in patients with mood and anxiety disorders. The aim of this study was to investigate whether CA is associated with enhanced cortisol reactivity to psychosocial stress in Social Anxiety Disorder (SAD).

Methods

Salivary cortisol levels before, during, and after exposure to psychosocial stress (i.e., Trier Social Stress Task, TSST) in SAD patients with a history of childhood abuse (SAD + CA, n = 9) were compared to cortisol levels in SAD patients without a history of childhood abuse (SAD − CA, n = 9), patients with PTSD related to childhood abuse (n = 16), and healthy controls without a history of childhood abuse (n = 16).

Results

Analyses showed that the SAD + CA group had a strongly increased cortisol reactivity (mean peak: 17.5 ± 1.9 nmol/l) compared to SAD − CA (mean peak: 9.0 ± 1.1 nmol/l), PTSD (mean peak: 9.0 ± 1.1 nmol/l) and healthy controls (mean peak: 9.6 ± 1.4 nmol/l), whereas baseline cortisol levels did not differ. The enhanced increase in the SAD + CA group was not explained by stronger anxiety in response to the TSST.

Conclusions

Consistent with the findings in depression, these results show for the first time that childhood abuse is also associated with strongly increased cortisol reactivity in SAD. When replicated in a larger sample, these findings may have important implications for the treatment of SAD.     

Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson's disease

DJ-1 is a multifunctional protein whose loss of function by gene mutations may play a causative role for familial Parkinson's disease (PD). A recent study has shown that the expression of this molecule is upregulated in both brains and cerebrospinal fluids (CSF) in various neurological disorders, including sporadic PD, Alzheimer's disease (AD) and stroke, raising a possibility that DJ-1 could be a potential biomarker for these diseases. In this context, the main objective of the present study was to determine if DJ-1 was increased in the plasma of PD patients. For this purpose, blood plasma samples collected from sporadic PD patients, dementia with Lewy bodies (DLB) and healthy age-matched controls were analyzed by immunoblotting and enzyme-linked immunosorbent assay. The results showed that the plasma DJ-1 levels in PD (n = 104) were higher than those in control (n = 80) (p < 0.05). Moreover, the plasma DJ-1 levels in the advanced stage of PD (n = 52, Yahr III–IV) were higher than those in the early stage of PD (n = 52, Yahr I–II) (p < 0.05), demonstrating that the plasma DJ-1 was correlated with the disease severity in PD. Plasma DJ-1 levels were also significantly higher in DLB (n = 30) compared with both controls and early stage of PD (p < 0.01). Taken together, these results suggest that the plasma DJ-1 could be a useful biomarker for the evaluation of the disease severity in PD and possibly in other Lewy body diseases.     

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate (‘urethane’; 1.2 mg kg⁻¹), ketamine/xylazine (ket/xyl; 80/10 mg kg⁻¹), or normal saline. Following each of the three interventions, breathing was monitored during 15 min exposures to normoxia (room air), hypoxia (10% O₂) and hypoxia + CO₂ (10% O₂, 5% CO₂). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p < 0.001), and decreased the hypocapnia-dependent component of this response (p < 0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p = 0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.     

Cerebrospinal fluid from patients with multiple system atrophy promotes in vitro α-synuclein fibril formation

The aggregation of α-synuclein (αS) in the central nervous system (CNS) is the hallmark of multiple system atrophy (MSA) and Lewy body diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) (α-synucleinopathies). To test the hypothesis that patients with α-synucleinopathies have a CNS environment favorable for αS aggregation, we examined the influence of cerebrospinal fluid (CSF) from patients with MSA (n = 20), DLB (n = 8), and PD (n = 10) on in vitro αS fibril (fαS) formation at pH 7.5 and 37 °C using fluorescence spectroscopy with thioflavin S, compared with those with hereditary spinocerebellar ataxia (hSCA) (n = 16), and tension-type headache (n = 7). CSF from MSA patients (MSA-CSF) promoted fαS formation more strongly than PD-, hSCA-, or headache-CSF. By electron microscopic analyses, the width of fαS formed in MSA-CSF was significantly greater than others. MSA may have a CSF environment particularly favorable for fαS formation.     

High perceived stress in relation to life events is associated with blunted cardiac reactivity

The current study examined whether the perception of life stress related to cardiovascular reactivity. Participants (n = 100) completed the Perceived Stress Scale, the Undergraduate Stress Questionnaire, and undertook a standard mental arithmetic stress task. Blood pressure and pulse rate were measured at baseline, during, and following stress task exposure. Reactivity was the difference between stress and baseline cardiovascular activity. A perceived stress difference score (PSDS) was calculated by subtracting the Undergraduate Stress Questionnaire scores from the Perceived Stress Scale scores. Two groups were created: high PSDS (n = 15; PSDS at least 1 SD above the mean) and low PSDS (n = 15; PSDS at least 1 SD below the mean). There was a significant difference between groups in pulse rate reactivity, F(1,28) = 8.73, p = .006, η² = .24. High PSDS scores were associated with significantly lower pulse rate reactions to stress. Those who perceived their lives as more stressful than their actual stress exposures justified would appear to be characterised by blunted cardiac reactivity.     

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO₂ sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO₂ sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO₂ exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/(kg day)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p > 0.05), although tidal volume (V_T) was reduced in BN rats (p < 0.05). There were also minimal effects of fluoxetine on CO₂ sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and V_T during hypercapnia in BN rats (p < 0.05). The augmented CO₂ response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p < 0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO₂ sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO₂ sensitivity in the BN rat.     

Physicians’ reactions to uncertainty in the context of shared decision making

Objective

Physicians’ reactions towards uncertainty may influence their willingness to engage in shared decision making (SDM). This study aimed to identify variables associated with physician's anxiety from uncertainty and reluctance to disclose uncertainty to patients.

Methods

We conducted a cross-sectional secondary analysis of longitudinal data of an implementation study of SDM among primary care professionals (n = 122). Outcomes were anxiety from uncertainty and reluctance to disclose uncertainty to patients. Hypothesized factors that would be associated with outcomes included attitude, social norm, perceived behavioral control, intention to implement SDM in practice, and socio-demographics. Stepwise linear regression was used to identify predictors of anxiety from uncertainty and reluctance to disclose uncertainty to patients.

Results

In multivariate analyses, anxiety from uncertainty was influenced by female gender (β = 0.483; p = 0.0039), residency status (1st year: β = 0.600; p = 0.001; 2nd year: β = 0.972; p < 0.001), and number of hours worked per week (β = −0.012; p = 0.048). Reluctance to disclose uncertainty to patients was influenced by having more years in formal education (β = −1.996; p = 0.012).

Conclusion

Variables associated with anxiety from uncertainty differ from those associated with reluctance to disclose uncertainty to patients.

Practice implications

Given the importance of communicating uncertainty during SDM, measuring physicians’ reactions to uncertainty is essential in SDM implementation studies.     

Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process

The aim of this study was to investigate the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of Parkinson's disease (PD). We employed high-performance liquid chromatography (HPLC) using an electrochemical detector to measure concentrations of the reduced and oxidized forms of coenzymeQ-10 (CoQ-10) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 20 patients with PD and 20 age-matched controls with no neurological disease. The percentage of oxidized to total CoQ-10 (%CoQ-10) in the CSF of the PD group (80.3 ± 17.9%) was significantly higher than in the control group (68.2 ± 20.4%, P < 0.05). In addition, the concentration of 8-OHdG in the CSF of PD patients was greater than in the CSF of controls (P < 0.0001) and was positively correlated with the duration of illness (r_s = 0.87, P < 0.001). Finally, the %CoQ-10 was correlated with concentrations of 8-OHdG in the CSF of PD patients (r_s = 0.56, P < 0.01). The present study suggests that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early PD development.     

Psychometric assessment of female overactive bladder syndrome and antimuscarinics-related effects

Objectives

To investigate the characteristics of psychological distress (PD), personality traits, and family support in women with overactive bladder syndrome (OAB), and the effects of antimuscarinic treatment.

Study design

Women with and without OAB (age- and body mass index [BMI]-matched control group) were prospectively enrolled; they recorded bladder diaries, underwent urodynamic studies, and completed PD, personality traits, and filled family support questionnaires before and after antimuscarinic treatment. OAB women underwent treatment with tolterodine or solifenacin for 12 weeks. The control group completed questionnaires.

Main outcome measures

The differences in PD, personality traits, and family support scores between both groups, and the changes after antimuscarinic treatment in OAB women.

Results

Eighty-five women with OAB (tolterodine, n = 42; solifenacin, n = 43) and 65 without OAB completed the studies. Linear regression analysis with age and BMI adjustment revealed: coefficients of OAB were significant (all P < 0.05) for somatic complaints (mean: 0.87 vs. 0.63, coefficient = 0.21), obsessive–compulsive symptoms (0.69 vs. 0.44, coefficient = 0.25), anxiety symptoms (0.42 vs. 0.27, coefficient = 0.14), General Symptom Index (GSI, 0.48 vs. 0.33, coefficient = 0.14), neuroticism (9.23 vs. 5.17, coefficient = 3.73), and extroversion–introversion (13.64 vs. 15.25, coefficient = −1.73). Anxiety symptoms (0.42 vs. 0.36) and GSI (0.48 vs. 0.39) improved after antimuscarinics (all P < 0.05). High Overactive Bladder Symptom Score questionnaire score (coefficient = −0.39), low hostility score (coefficient = 2.11), and high additional symptoms score (coefficient = −1.46) were associated with good therapeutic effect (all P < 0.05).

Conclusions

OAB women experience more PD, neuroticism, and introversion than asymptomatic women, and antimuscarinics could improve PD.     

Toll like receptors in self-recovering hepatitis E patients with or without pregnancy

Hepatitis E virus (HEV) causes high mortality among pregnant women. Pathogenesis of HEV, especially during pregnancy, is poorly understood. Our aim was to assess the role of Toll-like-receptors (TLRs) in hepatitis E patients with pregnancy (Antenatal care, ANC) or without pregnancy (non-ANC). The patient categories included acute-phase, non-ANC (n = 46) and ANC patients (2nd/3rd trimesters, n = 13) and non-ANC patients (n = 31) during convalescence. Controls included apparently healthy non-ANC (n = 30) and ANC subjects in the first (n = 10) and later (2nd/3rd, n = 20) trimesters. TLR2/TLR3/TLR4/TLR7/TLR8 levels were determined by flow-cytometry. Cytokine responses induced by TLR-specific-ligands-stimulated-PBMCs from ANC/non-ANC-patients and TLR-signaling-molecules (non-ANC-patients) were measured. PBMCs were used to assess gene expression levels by TaqMan-Low-Density-Array.     

Preliminary evidence of association between EFHC2, a gene implicated in fear recognition,and harm avoidance

Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p = 0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r² = 0.022; nominal p = 0.022) and PD (OR = 2.64; nominal p = 0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association.     

Olfactory loss and nigrostriatal dopaminergic denervation in the elderly

Olfactory dysfunction may precede common neurodegenerative disorders in the elderly, such as Alzheimer (AD) or Parkinson disease (PD). However, pathobiological mechanisms of olfactory loss in the elderly are poorly understood. Although nigrostriatal dopaminergic denervation is a key patholobiological feature of PD, age-associated nigrostriatal denervation (AASDD) occurs also with normal aging and can be more prominent in some elderly. We investigated the relationship between AASDD and olfactory performance in community-dwelling subjects. Community-dwelling subjects (n = 73, 44 F/29 M, mean age 64.0 ± 16.4, range 20–85) underwent brain dopamine transporter (DAT) [¹¹C]2-β-carbomethoxy-3β-(4-fluorophenyl) tropane (β-CFT) positron emission tomography (PET) imaging and olfactory assessment using the 40-odor University of Pennsylvania Smell Identification Test (UPSIT). Subjects with clinical or DAT PET evidence of Parkinson disease (PD) were not eligible for the study. AASDD was defined based on normative data in young and middle-aged subjects. Compared to a mild and general linear decline in odor identification observed in most subjects (R² = 0.18, P = 0.0002), there were 13 subjects who deviated below the 5% confidence interval level in age-predicted UPSIT scores. Analysis limited to elderly subjects 60 years and over demonstrated a significant association between poor smell (n = 10 out of 49, 20.4%) and AASDD (χ² = 4.4, P < 0.05). There is a significant association between olfactory dysfunction and more prominent nigrostriatal denervation in the elderly. Olfactory assessment may have potential as a screening tool to detect age-accelerated neurodegeneration in the elderly.     

Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model

Purpose

This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl₂)-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation.

Methods

Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5 M CaCl₂ or normal saline (NaCl). After 12 weeks, animals were euthanized, and CaCl₂-treated, CaCl₂-untreated (n = 12) and NaCl-treated aortic segments (n = 12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry.

Results

Despite similar external diameters among CaCl₂-treated, non-CaCl₂-treated and NaCl-treated segments, aneurymal alteration (n = 6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n = 12, 100%) were demonstrated in CaCl₂-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl₂-treated segments (all p < 0.01), with trends of elevation in CaCl₂-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p < 0.01) in intima and media for CaCl₂-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments.

Conclusion

This study establishes a TAA model by periarterial CaCl₂ exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.     

Genetic variation of CHRNA4 does not modulate attention in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder, characterised by cognitive decline and attentional impairment. Recently, variation in CHRNA4 (rs1044396) has been shown to affect visual and auditory function, affecting speed and attention, in healthy adults. An association between CHRNA4 variation and PD has not been shown. To determine the link between CHRNA4 variation and attentional deficit in PD. A genotype–phenotype correlation between the common CHRNA4:rs1044396 variant and several baseline parameters of attention was carried out in a large cohort of PD cases (n = 222) and controls (n = 159). We identified significant associations to measures of attention in PD patients compared to controls. However, we found no significant link to CHRNA4:rs1044396 genotypes to baseline attention variables in PD or in controls. We conclude that CHRNA4:rs1044396 genotypes do not significantly influence the attentional deficit found in PD patients. Contrary to previous studies, we also found no significant influence in healthy age-matched controls.