Updates on the psychological and psychiatric aspects of the Ehlers-Danlos syndromes and hypermobility spectrum disorders.

The field of the psychiatric and psychological aspects of Ehlers-Danlos syndromes (EDS) has been understudied and neglected for many years. People with EDS are often classified as "somatizers" by untrained clinicians. However, research on the biological basis of EDS is improving our understanding of the physiology and psychopathology of the disorder. In this article, we consider the literature on the psychopathological dimensions associated with EDS as well as the EDS symptoms in psychiatric conditions since our review in 2017. Literature confirms that psychological processes (i.e., fear, emotional distress, or negative emotions) in EDS have a significant impact on the outcomes of EDS. Common systemic associations are found between anxiety disorders and EDS as well as significant correlations with neurodevelopmental, eating, mood, and sleep disorders. There is limited but increasing evidence of an association between EDS and suicidal thoughts and behaviors, which should be further explored. The broad spectrum of human anxiety and associated somatic symptoms (beyond anxiety disorders) appears to be the core of the psychopathology in EDS and therefore, detecting and assessing EDS might be a new opportunity for psychiatric nosology to develop more inclusive phenotypes like the Neuroconnective Phenotype that include both somatic and psychological manifestations.

The ALPIM (Anxiety, Laxity, Pain, Immune, and Mood) Syndrome in Adolescents and Young Adults: A Cohort Study.

OBJECTIVE: ALPIM (anxiety, laxity, pain, immune, and mood) syndrome has been previously described in adults. The authors aimed to identify its occurrence in adolescents and confirm its existence in adults. Given the association of the disorder with somatic symptoms, separation anxiety disorder (SAD) was explored as an ALPIM comorbidity. METHODS: Medical records of patients aged 11-34 with a diagnosis of depression or anxiety (panic disorder, SAD, social anxiety or generalized anxiety disorder) seen during a 1-year period were reviewed. Data were collected on the presence of ALPIM comorbidities. Analyses were conducted to detect their co-occurrence and evaluate possible predictors of the ALPIM syndrome. RESULTS: Inclusion criteria were met by 185 patient charts. A significant association was observed between the ALPIM comorbidities with 20 study subjects (10.8%) meeting criteria for ALPIM syndrome (patients with one or more diagnoses from each ALPIM domain). Patients with SAD had increased odds of being diagnosed with ALPIM (odds ratio=7.14, 95% CI=2.48-20.54, p<0.001). Neither major depression nor generalized anxiety disorder was found to be predictive of ALPIM syndrome. There was no difference in the prevalence of ALPIM-related comorbidities between study subjects <18 years old compared with those ≥18 years old. CONCLUSIONS: These findings reestablish the association of distinct psychiatric and nonpsychiatric conditions described as the ALPIM syndrome. Furthermore, the syndrome may present during adolescence. SAD may be an independent predictive factor for the occurrence of ALPIM syndrome. Patients with individual ALPIM comorbidities should be assessed for the syndrome, especially if they have a history of SAD.

Patients with Moderate to Severe Psoriasis Associate with Higher Risk of Depression and Anxiety Symptoms: Results of a Multivariate Study of 300 Spanish Individuals with Psoriasis.

Psoriasis is a chronic skin disease associated with considerable physical and psychological comorbidities. Stress and emotional disturbances have been implicated in both triggering the onset and exacerbation of psoriasis. In order to determine the level of perceived stress and mood alterations in patients with psoriasis and their association with disease severity, 300 individuals completed diverse validated questionnaires assessing stress and psychological mood. Evaluation of perception of disease was also measured. A significant association between psoriasis severity and mood, emotional disturbances and an impact on assessments of the quality of life were observed. Particularly, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale and Hospital Anxiety and Depression Scale for Depression detected a significant risk for depression in relation to the disease severity. The association between depression features, anxiety and perceived stress with psoriasis severity is important and can influence the appropriate management of psoriasis.

Joint hypermobility is also associated with anxiety disorders in the elderly population.

BACKGROUND: Anxiety disorders (AD) are very prevalent in the elderly, tend to compromise quality of life, and generate substantial costs. Considering that the prevention and early detection of anxiety may be relevant to increase health gains in older adults, it would be of great interest to identify whether the joint hypermobility syndrome (JHS) is also related to anxiety disorders in this age range. METHODS: Cross-sectional data was collected in a sample of 108 subjects in a rural town in Spain. Instruments included Spielberger STAI, a modified Wolpe Fear Survey Schedule, General health Questionnaire (GHQ)-28, and the anxiety and mood disorders section of the SCID, to assess past year prevalence of anxiety disorders. JHS was evaluated by trained examiners using the "Hospital del Mar criteria". RESULTS: Among the 108 subjects (55% women, 45% men) over 60 years old, 21.3% meet criteria for JHS. These subjects scored significantly higher in both State (F = 5.53; p = 0.02) and Trait (F = 4.68; p = 0.03) anxiety and the GHQ 28 (F = 6.29; p = 0.01). Compared with non JHS subjects, they had more AD (34.8% vs. 11.8%; x2  = 6.90; p = 0.02) and mood disorders (30.4% vs. 10.6%; x2  = 5.65; p = 0.041) in the past year prevalence. A multiple logistic regression analysis showed that both JHS (ß = 0.196; p = 0.04) and fears (ß = 0.34; p = 0.001) are predictors of AD (r2  = 188; p = 0.001) in this population. CONCLUSIONS: Joint hypermobility syndrome is associated with anxiety in the elderly population, and it may be used as a physical marker for AD among subjects within this age range. Copyright © 2017 John Wiley & Sons, Ltd.

Low- and high-anxious hypermobile Ehlers-Danlos syndrome patients: comparison of psychosocial and health variables.

Despite the frequent co-ocurrence of hypermobile Ehler-Danlos syndrome (hEDS) and pathological anxiety, little is known about the psychosocial and health implications of such comorbidity. Our aim was to explore the association between high levels of anxiety and psychosocial (catastrophizing, kinesiophobia, somatosensory amplification, social support and functioning), health (pain, fatigue, BMI, tobacco/alcohol use, depression, diagnosis delay, general health), and sociodemographic factors in people with hEDS. In this cross-sectional study, 80 hEDS patients were divided into two groups according to self-reported anxiety levels: low and high. Psychosocial, sociodemographic and health variables were compared between the groups. Forty-one participants reported a high level of anxiety (51.2%). No differences were found in the sociodemographic variables between high-anxious and low-anxious patients. The percentage of participants with severe fatigue and high depressive symptomatology was significantly higher in the high-anxious group (80.5 vs 56.4; 26.8 vs 12.8%, respectively). High-anxious hEDS patients also showed significantly higher levels of pain catastrophizing, somatosensory amplification as well as a poorer social functioning and general health. Multivariate analyses showed that somatosensory amplification, pain catastrophizing and poor social functioning are variables that increase the probability of belonging to the high-anxious group. Despite limitations, this first study comparing high-anxious versus low-anxious hEDS patients with respect to health aspects, highlight the importance of considering the psychosocial factors (many susceptible to modification), to improve the adjustment to this chronic condition and provide support to those affected through a biopsychosocial approach.

Pain management in the Ehlers-Danlos syndromes.

Chronic pain in the Ehlers-Danlos syndromes (EDS) is common and may be severe. According to one study, nearly 90% of patients report some form of chronic pain. Pain, which is often one of the first symptoms to occur, may be widespread or localized to one region such as an arm or a leg. Studies on treatment modalities are few and insufficient to guide management. The following is a discussion of the evidence regarding the underlying mechanisms of pain in EDS. The causes of pain in this condition are multifactorial and include joint subluxations and dislocations, previous surgery, muscle weakness, proprioceptive disorders, and vertebral instability. Affected persons may also present with generalized body pain, fatigue, headaches, gastrointestinal pain, temporomandibular joint pain, dysmenorrhea, and vulvodynia. Pain management strategies may be focused around treating the cause of the pain (e.g., dislocation of a joint, proprioceptive disorder) and minimizing the sensation of pain. Management strategies for chronic pain in EDS includes physical therapy, medications, as well as durable medical equipment such as cushions, compressive garments, and braces. The different modalities are discussed in this paper. © 2017 Wiley Periodicals, Inc.

Psychiatric and psychological aspects in the Ehlers-Danlos syndromes.

There is increasing amount of evidence pointing toward a high prevalence of psychiatric conditions among individuals with hypermobile type of Ehlers-Danlos syndrome (JHS/hEDS). A literature review confirms a strong association between anxiety disorders and JHSh/hEDS, and there is also limited but growing evidence that JHSh/hEDS is also associated with depression, eating, and neuro-developmental disorders as well as alcohol and tobacco misuse. The underlying mechanisms behind this association include genetic risks, autonomic nervous system dysfunction, increased exteroceptive and interoceptive mechanisms and decreased proprioception. Recent neuroimaging studies have also shown an increase response in emotion processing brain areas which could explain the high affective reactivity seen in JHS/hEDS. Management of these patients should include psychiatric and psychological approaches, not only to relieve the clinical conditions but also to improve abilities to cope through proper drug treatment, psychotherapy, and psychological rehabilitation adequately coupled with modern physiotherapy. A multidimensional approach to this "neuroconnective phenotype" should be implemented to ensure proper assessment and to guide for more specific treatments. Future lines of research should further explore the full dimension of the psychopathology associated with JHS/hEDS to define the nature of the relationship. © 2017 Wiley Periodicals, Inc.

[Detecting and measuring functional and organic disease in general population: Development and validation of TOPYPS clinical scale]. / Detección y medición de la enfermedad funcional y orgánica en población general: desarrollo y validación de la escala clínica TOPYPS.

OBJECTIVE: To develop and validate the TOPYPS scale, an instrument designed to: (i)detect with a high degree of suspicion the most frequent functional pathologies according to standard diagnostic criteria, and (ii)to assess the physical health in the general population quickly, comprehensive and reliable. DESIGN: Validation of a scale. LOCATION: Primary Care Centre, Barcelona. PARTICIPANTS: The scale was administered to 67 randomly selected adults. MEASUREMENTS: TOPYPS scale was administered to 67 adults randomly selected from a primary care setting in Barcelona, Spain. TOPYPS has six sections based on body systems, each one scored according to the degree of interference in daily activity, type of treatment received, and prognostic of the reported illnesses in each section. Test-retest reliability completions were on two separate occasions one week apart. Validity was then tested by comparing the results with the clinical examination conducted by two different specialists in general practice (gold standard). RESULTS: Repeatability (test-retest) and inter-rater agreement for each of the six sections and for the total score were satisfactory. Validity was acceptable both for content and construct, according to their correlation with the gold standard. CONCLUSIONS: TOPYPS displayed good psychometrical properties. It is a suitable tool to detect and measure functional and organic diseases in general population.

A Novel Anxiety and Affective Spectrum Disorder of Mind and Body-The ALPIM (Anxiety-Laxity-Pain-Immune-Mood) Syndrome: A Preliminary Report.

The authors describe a spectrum disorder comprising a core anxiety (A) disorder and four domains: joint laxity (L), chronic pain syndromes (P), immune disorders (I), and mood disorders (M)-dubbed the ALPIM syndrome. This study examined 76 consecutive outpatients with an anxiety disorder plus at least one somatic condition from three domains. More than 80% of the patients had panic attacks, fibromyalgia, and major depressive episodes. Associations were found between joint laxity and bipolar III, headache with bipolar II, and bipolar II with chronic fatigue syndrome. Significant relationships were demonstrated within and between domains, validating ALPIM as a syndrome.

Clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder in a psychiatric emergency service.

INTRODUCTION: To analyze factors associated with clinical observation, pharmacotherapy and referral on discharge of patients with anxiety disorder (AD) seeking care at a psychiatric emergency unit. METHOD: A total of 5003 consecutive visits were reviewed over a three-year period at a psychiatric emergency service in a tertiary university hospital. Data collected included sociodemographic and clinical information as well as the Global Assessment of Functioning (GAF) and the Severity Psychiatric Illness (SPI) scale scores. RESULTS: Of all the visits, 992 (19.8%) were diagnosed of AD. Of these, 19.6% required clinical observation and 72.2% were referred to a psychiatrist at discharge. Regression analysis showed that referral to psychiatry was associated with being male, native, psychiatric background, greater severity, lower global functioning, and behavioral disorders. Clinical observation (in a box) was associated with being female, greater severity, and psychotic or behavioral symptoms. Prescription of benzodiazepines was associated with anxiety, no history of addiction, and lower global functioning. Antidepressants were associated with being a native, anxiety with no history of addiction, and lower functioning. Antipsychotics were associated with being native, psychiatric background (not addiction), anxiety, and lower functioning. CONCLUSION: Behavior, psychiatric background and illness severity were determinants of referral to a specialist. Besides these, psychotic symptoms and non-specific clinical symptoms were determinants of observation. Drug prescription in AD is less frequent if the main complaint is not anxiety and depends more on the level of functioning than on that of severity.

An independent components and functional connectivity analysis of resting state fMRI data points to neural network dysregulation in adult ADHD.

Spontaneous fluctuations can be measured in the brain that reflect dissociable functional networks oscillating at synchronized frequencies, such as the default mode network (DMN). In contrast to its diametrically opposed task-positive counterpart, the DMN predominantly signals during a state of rest, and inappropriate regulation of this network has been associated with inattention, a core characteristic of attention-deficit/hyperactivity disorder (ADHD). To examine whether abnormalities can be identified in the DMN component of patients with ADHD, we applied an independent components analysis to resting state functional magnetic resonance imaging data acquired from 22 male medication-naïve adults with ADHD and 23 neurotypical individuals. We observed a stronger coherence of the left dorsolateral prefrontal cortex (dlPFC) with the DMN component in patients with ADHD which correlated with measures of selective attention. The increased left dlPFC-DMN coherence also surfaced in a whole-brain replication analysis involving an independent sample of 9 medication-naïve adult patients and 9 controls. In addition, a post hoc seed-to-voxel functional connectivity analysis using the dlPFC as a seed region to further examine this region's suggested connectivity differences uncovered a higher temporal coherence with various other neural networks and confirmed a reduced anticorrelation with the DMN. These results point to a more diffuse connectivity between functional networks in patients with ADHD. Moreover, our findings suggest that state-inappropriate neural activity in ADHD is not confined to DMN intrusion during attention-demanding contexts, but also surfaces as an insufficient suppression of dlPFC signaling in relation to DMN activity during rest. Together with previous findings, these results point to a general dysfunction in the orthogonality of functional networks.

Ectomorphic somatotype and joint hypermobility are linked in panic and agoraphobic patients: a case-control study.

OBJECTIVE: To test whether there is an association between somatotype measures, joint hypermobility (JH), and panic and/or agoraphobia (PA). METHOD: Sociodemographic characteristics, somatotype, and JH status were assessed in 60 patients (30 men and 30 women) with PA and 60 non-clinical controls, matched by age and gender. RESULTS: Patients and controls categorized by gender did not differ in terms of age, educational degree, marital status, or labour situation. There were significant differences between mean somatotype groups both in men and women. Men and women somatotype patients were significantly less endomorphic and more ectomorphic than controls. Hypermobility was significantly more frequent in both male and female patients. In the entire sample, 38.3% of patients and 13.3% of controls were categorized as ectomorphic (χ(2) = 8.5, p = 0.004). After adjusting for age and sex, ectomorphic somatotype was independently related to JH status [OR = 3.25, 95% CI 1.35-7.8, p = 0.008]. CONCLUSIONS: Since PA may be associated with JH, it is suggested that the relationship found between panic and ectomorphic somatotype might be mediated through JH.

Olfaction in affective and anxiety disorders: a review of the literature.

BACKGROUND: Olfaction and its relation to mental health is an area of growing interest. Brain areas linked to olfaction partially overlap with brain areas involved in psychiatric disorders; consequently, the study of olfactory function allows us to explore the integrity of these brain areas with a non-invasive and effective method. Accordingly, the aim of this paper is to review olfactory function in affective and anxiety disorders. METHODS: For this purpose, an extensive literature review of English-language studies on olfactory function in patients with the aforementioned pathologies was performed using several online databases. A manual search of relevant journals and books as well as reference lists from selected papers was also performed. RESULTS: The available data show that depressed patients are usually characterised by preserved olfactory function, except for detection threshold, where contrasting reports have been found. Bipolar disorder has been studied to a lesser extent, but the findings have shown a lack of impairment in most cases. Research on seasonal affective disorders is scant, and future studies are needed to make conclusions. Anxiety disorders have been scarcely approached, but the results note identification deficits in obsessive-compulsive and posttraumatic stress disorders. CONCLUSIONS: Olfactory assessment appears to be a complementary, valuable research tool in the study of psychiatric disorders. However, further investigation is needed to improve our understanding of olfactory function in these disorders.

EROL scale: a new behavioural olfactory measure and its relationship with anxiety and depression symptoms.

INTRODUCTION: The main objective of this study was to develop and validate a new olfactory measure that assesses the influence of olfaction on several emotional, behavioural, and cognitive issues: The Relational Scale of Olfaction (EROL). A secondary objective was to explore the relationship between the olfactory function and the anxiety and depression symptoms by means of EROL and the Hospital Anxiety and Depression Scale (HADS). A positive relationship between anxiety symptoms and the olfactory function was hypothesized. Regarding depressive symptoms, a significant relationship with the olfactory scores was not expected. METHOD: Psychometric properties of EROL scale and correlations between HADS and EROL were tested in a sample from the general population. RESULTS: EROL showed an adequate level of test-retest reliability (ICC=.748) and good internal consistency (Cronbach's alpha=.761). Convergent validity with other olfactory measures was satisfactory. A one-factor solution was found for the scale. HADS showed a significant relationship with EROL (r=.280, p<.01), but the analysis through dimensions revealed that only the anxiety subscale correlated significantly and moderately with the olfactory measure (r=.325, p<.001), whereas the correlation with the depression subscale was non-significant (r=.146, p>.05). CONCLUSIONS: Given that EROL displayed good psychometrical properties, it appears as a suitable tool to assess the olfactory function in general population. The relationship between this olfactory scale and anxiety symptoms found in this study is an interesting issue that requires further research.

Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

Introduction: The link between anxiety disorders and joint hypermobility syndrome (now under hypermobility spectrum disorders, which include hypermobile Ehlers-Danlos syndrome) has been widely replicated over the past 30 years and has grown beyond the initial nosological limits. To integrate clinical and research progress in this field, a new neuroconnective endophenotype (NE) and its corresponding instrument, the Neuroconnective Endophenotype Questionnaire (NEQ), have been developed. This new clinical construct, created with the active participation of patients, includes both somatic and psychological dimensions and symptoms and resilience items. Methods: The NE includes five dimensions: (1) sensorial sensitivity, (2) body signs and symptoms, (3) somatic conditions, (4) polar behavioral strategies, and (5) psychological and psychopathological dimensions. The NEQ information is collected through four self-administered questionnaires (sensorial sensitivity, body signs and symptoms, polar behavioral strategies, and psychological characteristics) and a structured diagnostic part that should be completed by a trained observer. This hetero-administered part incorporates (a) psychiatric diagnoses (using structured criteria, e.g., MINI), (b) somatic disorders diagnosis, using structured criteria, and (c) assessment of joint hypermobility criteria. Results: In a sample of 36 anxiety cases with 36 matched controls, the NEQ obtained high scores for test-retest, inter-rater reliability, and internal consistency. As for predictive validity, cases and controls significantly differed in all five dimensions and hypermobility measurements. Discussion: We can conclude that the NEQ has achieved acceptable reliability and validity values and, therefore, is ready to be used and tested in different samples. This original and consistent construct including somatic and mental items may improve clinical specificity, the search for more comprehensive therapies, and their genetic and neuroimaging bases.

Corrigendum: Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

[This corrects the article DOI: 10.3389/fmed.2023.1039223.].

Effectiveness of Acceptance and Commitment Therapy (ACT) for the Management of Postsurgical Pain: Study Protocol of a Randomized Controlled Trial (SPINE-ACT Study).

Research on the use of Acceptance and Commitment Therapy (ACT) for patients with degenerative lumbar pathology awaiting surgery are limited. However, there is evidence to suggest that this psychological therapy may be effective in improving pain interference, anxiety, depression, and quality of life. This is the protocol for a randomized controlled trial (RCT) to evaluate the effectiveness of ACT compared to treatment as usual (TAU) for people with degenerative lumbar pathology who are candidates for surgery in the short term. A total of 102 patients with degenerative lumbar spine pathology will be randomly assigned to TAU (control group) or ACT + TAU (intervention group). Participants will be assessed after treatment and at 3-, 6-, and 12-month follow-ups. The primary outcome will be the mean change from baseline on the Brief Pain Inventory (pain interference). Secondary outcomes will include changes in pain intensity, anxiety, depression, pain catastrophizing, fear of movement, quality of life, disability due to low back pain (LBP), pain acceptance, and psychological inflexibility. Linear mixed models will be used to analyze the data. Additionally, effect sizes and number needed to treat (NNT) will be calculated. We posit that ACT may be used to help patients cope with the stress and uncertainty associated with their condition and the surgery itself.

Response inhibition and reward anticipation in medication-naïve adults with attention-deficit/hyperactivity disorder: a within-subject case-control neuroimaging study.

BACKGROUND: Previous research suggests that ADHD patients are characterized by both reduced activity in the inferior frontal gyrus (IFG) during response inhibition tasks (such as the Go-NoGo task), and reduced activity in the ventral striatum during reward anticipation tasks (such as the Monetary-Incentive-Delay [MID] task). However, no prior research has applied either of these paradigms in medication-naïve adults with ADHD, nor have these been implemented in an intrasubject manner. METHODS: The sample consisted of 19 medication-naïve adults with ADHD and 19 control subjects. Main group analyses were based on individually defined regions of interest: the IFG and the VStr for the Go-NoGo and the MID task respectively. In addition, we analyzed the correlation between the two measures, as well as between these measures and the clinical symptoms of ADHD. RESULTS: We observed reduced bilateral VStr activity in adults with ADHD during reward anticipation. No differences were detected in IFG activation on the Go-NoGo paradigm. Correlation analyses suggest that the two tasks are independent at a neural level, but are related behaviorally in terms of the variability of the performance reaction time. Activity in the bilateral VStr but not in the IFG was associated negatively with symptoms of hyperactivity/impulsivity. CONCLUSIONS: Results underline the implication of the reward system in ADHD adult pathophysiology and suggest that frontal abnormalities during response inhibition performance may not be such a pivotal aspect of the phenotype in adulthood. In addition, our findings point toward response variability as a core feature of the disorder.