Naia Sáez-Francàs

Could Mitochondrial Dysfunction Be a Differentiating Marker Between Chronic Fatigue Syndrome and Fibromyalgia

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

Validez de criterio y concurrente de la versión española de la Conners Adult ADHD Diagnostic Interview for DSM-IV

INTRODUCTION Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in adulthood. Its diagnosis requires a retrospective evaluation of ADHD symptoms in childhood, the continuity of these symptoms in adulthood, and a differential diagnosis. For these reasons, diagnosis of ADHD in adults is a complex process which needs effective diagnostic tools. AIM To analyse the criterion validity of the CAADID semi-structured interview, Spanish version, and the concurrent validity compared with other ADHD severity scales. METHODS An observational case-control study was conducted on 691 patients with ADHD. They were out-patients treated in a program for adults with ADHD in a hospital. RESULTS A sensitivity of 98.86%, specificity 67.68%, positive predictive value 90.77% and a negative predictive value 94.87% were observed. Diagnostic precision was 91.46%. The kappa index concordance between the clinical diagnostic interview and the CAADID was 0.88. Good concurrent validity was obtained, the CAADID correlated significantly with WURS scale (r=0.522, P<.01), ADHD Rating Scale (r=0.670, P<.0.1) and CAARS (self-rating version; r=0.656, P<.01 and observer-report r=0.514, P<.01). CONCLUSION CAADID is a valid and useful tool for the diagnosis of ADHD in adults for clinical, as well as for research purposes.

The Association of Apathy With Central Fatigue Perception in Patients With Parkinson's Disease

This study was designed to evaluate the association of different apathy conceptual domains with central fatigue perception in Parkinsons disease (PD), taking into consideration other nonmotor symptoms. To this end, 90 consecutive PD patients (66.7% men, mean age 61.44 ± 13.2 years) underwent a comprehensive neurological and psychiatric examination, including the Structured Clinical Interview for DSM-IV, Parkinson Fatigue Scale, Lille Apathy Rating Scale, Hamilton Depression Scale, and State-Trait Anxiety Inventory. A linear regression model was applied to analyze the relationship between apathy and its different conceptual domains with fatigue severity. Thirty-seven (41.1%) patients presented fatigue. Its presence was associated with higher apathy total scores and with 2 of the 4 apathy conceptual domains (less intellectual curiosity and action initiation) with no associations in the emotion and self-awareness apathy domains. Patients with fatigue scored higher in depression (p < .001), anxiety trait (p < .001), and anxiety state (p = .006). Regression analysis identified that Lille Apathy Rating Scale total score (p = .008), intellectual curiosity and action initiation apathy subscores (p = .001 and p = .003) were associated with fatigue severity in patients with right predominant motor symptoms. Sex, age, disease duration, clinical stage, motor complications, prior psychiatric disorders, and treatment were not significantly associated with presence of fatigue. The findings suggest that some apathy-related domains are more frequent in fatigued PD and may be related with fatigue severity.

Relationship between poor decision-making process and fatigue perception in Parkinson's disease patients.

BACKGROUND Fatigue is a common non-motor symptom in Parkinsons disease patients. The reasons for its perception are not completely understood. One suggested possibility might be that perceived fatigue is related with abnormal interpretation of somatic symptoms. It has been described that somatic markers misinterpretation leads to poor decision-making. We hypothesized that fatigued Parkinsons disease patients would show poorer performance than non-fatigued in a decision-making task. METHODS To test our hypothesis, 89 Parkinsons disease patients were assessed for the presence of fatigue using the Parkinson Fatigue Scale. All patients were also administered scales evaluating psychopathology and neuropsychological tests, including the Iowa Gambling Task. RESULTS 33 (37.1%) patients fulfilled the established criteria for fatigue. In the univariate analysis, fatigued patients showed higher levels of anxiety (state: p = 0.001, trait: p < 0.001), impulsivity (p = 0.051), and depression (p < 0.001) than non-fatigued patients. No statistically significant differences in other neuropsychological test results (Stroop, Trail Making Test, Tower of London) were found between fatigued and non-fatigued patients except for the Iowa Gambling Task, in which fatigued patients showed poorer performance (p = 0.001) after controlling for confounding factors. CONCLUSIONS These results suggest that fatigued Parkinsons disease patients may present abnormal decision-making process, which may reflect abnormal processing of somatic markers when faced with an activity that requires effort.

The role of neuroticism, perfectionism and depression in chronic fatigue syndrome. A structural equation modeling approach

OBJECTIVE Previous studies have reported consistent associations between Neuroticism, maladaptive perfectionism and depression with severity of fatigue in Chronic Fatigue Syndrome (CFS). Depression has been considered a mediator factor between maladaptive perfectionism and fatigue severity, but no studies have explored the role of neuroticism in a comparable theoretical framework. This study aims to examine for the first time, the role of neuroticism, maladaptive perfectionism and depression on the severity of CFS, analyzing several explanation models. METHODS A sample of 229 CFS patients were studied comparing four structural equation models, testing the role of mediation effect of depression severity in the association of Neuroticism and/or Maladaptive perfectionism on fatigue severity. RESULTS The model considering depression severity as mediator factor between Neuroticism and fatigue severity is the only one of the explored models where all the structural modeling indexes have fitted satisfactorily (Chi square=27.01, p=0.079; RMSE=0.047, CFI=0.994; SRMR=0.033). Neuroticism is associated with CFS by the mediation effect of depression severity. This personality variable constitutes a more consistent factor than maladaptive perfectionism in the conceptualization of CFS severity.

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.

Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126). A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings.

Factores clínicos y psicopatológicos asociados a los trastornos del control de impulsos en la enfermedad de Parkinson

INTRODUCTION Impulse control disorders (ICD) constitute a complication that may arise during the course of Parkinsons disease (PD). Several factors have been linked to the development of these disorders, and their associated severe functional impairment requires specific and multidisciplinary management. The objective of this study was to evaluate the frequency of ICDs and the clinical and psychopathological factors associated with the appearance of these disorders. METHODS Cross-sectional, descriptive, and analytical study of a sample of 115 PD patients evaluated to determine the presence of an ICD. Clinical scales were administered to assess disease severity, personality traits, and presence of psychiatric symptoms at the time of evaluation. RESULTS Of the 115 patients with PD, 27 (23.48%) displayed some form of ICD; hypersexuality, exhibited by 14 (12.2%), and binge eating, present in 12 (10.1%), were the most common types. Clinical factors associated with ICD were treatment with dopamine agonists (OR: 13.39), earlier age at disease onset (OR: 0.92), and higher score on the UPDRS-I subscale; psychopathological factors with a significant association were trait anxiety (OR: 1.05) and impulsivity (OR: 1.13). CONCLUSIONS ICDs are frequent in PD, and treatment with dopamine agonists is the most important risk factor for these disorders. High impulsivity and anxiety levels at time of evaluation, and younger age at disease onset, were also linked to increased risk. However, presence of these personality traits prior to evaluation did not increase risk of ICD.

Chronic fatigue syndrome and personality: A case-control study using the alternative five factor model

Neuroticism is the personality dimension most frequently associated with chronic fatigue syndrome (CFS). Most studies have also shown that CFS patients are less extraverted than non-CFS patients, but results have been inconsistent, possibly because the facets of the extraversion dimension have not been separately analyzed. This study has the following aims: to assess the personality profile of adults with CFS using the Alternative Five-Factor Model (AFFM), which considers Activity and Sociability as two separate factors of Extraversion, and to test the discriminant validity of a measure of the AFFM, the Zuckerman-Kuhlman Personality Questionnaire, in differentiating CFS subjects from normal-range matched controls. The CFS sample consisted of 132 consecutive patients referred for persistent fatigue or pain to the Department of Medicine of a university hospital. These were compared with 132 matched normal population controls. Significantly lower levels of Activity and significantly higher levels of Neuroticism-Anxiety best discriminated CFS patients from controls. The results are consistent with existing data on the relationship between Neuroticism and CFS, and clarify the relationship between Extraversion and CFS by providing new data on the relationship of Activity to CFS.

Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients

Psychopathological disorders are frequent in chronic fatigue syndrome patients. The present study examines the presence of attention-deficit hyperactivity disorder (ADHD) in a sample of adult chronic fatigue syndrome (CFS) patients, and evaluates its clinical consequences in this population. CFS patients were assessed for childhood and adult ADHD by clinical interview and ADHD-specific scales. Psychopathological comorbidities were evaluated by clinical examination and questionnaires. Forty-seven of 158 CSF patients (29.7%) were diagnosed of childhood ADHD and in 33 (20.9%), the condition persisted into adulthood. CFS patients with adult ADHD had an earlier CSF onset, more severe anxiety and depression symptoms, and a higher risk of suicide than CFS patients without ADHD. Using lineal regression analysis, we found that depressive symptoms and ADHD severity were significant predictors of fatigue intensity. Consequently, ADHD may be common in CFS patients, and is associated with a more severe psychopathologic clinical profile.