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.

Current Knowledge on Gene-Environment Interactions in Personality Disorders: an Update.

PURPOSE OF REVIEW: We review the existing literature on gene-environment interactions (G×E) and epigenetic changes primarily in borderline personality disorder (BPD) but also in antisocial, schizotypal, and avoidant personality disorders. RECENT FINDINGS: Research supports that susceptibility genes to BPD or its underlying traits may be expressed under certain environmental conditions such as physical or childhood sexual abuse. Epigenetic modifications of neurodevelopment- and stress-related genes are suggested to underlie the relationship between early life adversary and borderline personality disorder. Only limited studies have investigated the role of gene-environment interactions and epigenetic changes in the genesis of antisocial, schizotypal, and avoidant personality disorders. Considering the lack of pharmacological treatment for most personality disorders, the emerging evidence on the critical role of G×E and epigenetic changes in the genesis of personality disorders could help develop more biologically oriented therapeutic approaches. Future studies should explore the potential of this new therapeutic dimension.

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.

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.

Joint hypermobility, anxiety and psychosomatics: two and a half decades of progress toward a new phenotype.

The strong association between a heritable collagen condition and anxiety was an unexpected finding that we first described in 1988 at the Hospital del Mar in Barcelona. Since then, several clinical and nonclinical studies have been carried out. In this paper, after summarizing the concept and diagnosis of joint hypermobility (hyperlaxity), we review case-control studies in both directions (anxiety in joint hypermobility and joint hypermobility in anxiety disorders) as well as studies on nonclinical samples, review papers and one incidence study. The collected evidence tends to confirm the strength of the association described two and a half decades ago. The common mechanisms that are involved in this association include genetics, autonomic nervous system dysfunctions and interoceptive and exteroceptive processes. Considering clinical and nonclinical data, pathophysiological mechanisms and the presented nosological status, we suggest a new Neuroconnective phenotype, which around a common core Anxiety-Collagen hyperlaxity, includes five dimensions: behavioral, psychopathology, somatic symptoms, somatosensory symptoms, and somatic illnesses. It is envisaged that new descriptions of anxiety disorders and of some psychosomatic conditions will emerge and that different nosological approaches will be required. The Neuroconnective model is a proposal that is under study and may be useful for clinical practice.

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.].

Joint hypermobility, fears, and chocolate consumption.

Our purpose was to evaluate joint hypermobility, an inherited disorder of the connective tissue significantly associated with anxiety disorders, in a sample of nonclinical students in relation to the frequency of severe fears and consumption of chocolate, coffee, cigarettes, and alcohol. One hundred fifty students completed the Hakim and Grahame Simple Questionnaire to detect hypermobility and the self-administered modified Wolpe Fear Scale (100 items). Severe fears and daily consumption of cigarettes, alcohol, coffee, and chocolate were compared with the hypermobility scores. We found significant differences when comparing severe fears between the groups with and without hypermobility (7.6 vs. 11; p = 0.001), reinforcing the hypothesis that the intensity of fears is greater in subjects with hypermobility. Only the frequency of chocolate intake was significantly higher among subjects with hypermobility (31.2% vs. 51.2%; p = 0.038) and may correspond to attempts of self-treatment of the collagen condition.

First Person Account COVID 19 Delirium in a Doctor: When Death Stalks the Mind.

Previous studies reported that 20-30% of COVID-19 patients will develop delirium during the hospitalization, achieving 70% in cases of severe illness. The risks factors and the consequences of delirium are well-documented in the literature; however, little is known about the personal experience of delirium. Delirium burden is common and tends to be distressing even after the delirium episode has resolved. Taking this in mind, the present work provides a first-person account of a doctor who acquired Covid-19 and developed bilateral pneumonia and had delirium and a complicate course of illness. During the course of his delirium, the patient recalled experiences of reality and unreality, complete disorientation, lack of control, strong emotions, and intense fear of dying which was significantly distressing. We anticipate that delirium burden will be common on these patients and family members and clinicians should be aware of this phenomenon in order to evaluate the neuropsychiatric consequences of this condition.

First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog.

There is a well-established relationship between joint hypermobility and anxiety in humans, that has not previously been investigated in other species. A population of 5575 assistance dogs were scored for both hip hypermobility and 13 behaviour characteristics using previously validated methods. Our results suggest a positive association between hip joint hypermobility and emotional arousal in domestic dogs, which parallel results found in people.

Joint hypermobility is a marker for anxiety in children. / La hiperlaxitud articular como marcador de ansiedad en niños.

BACKGROUND: Joint hypermobility syndrome (JHS) has been found to be associated with anxiety disorders in clinical and nonclinical populations, but to date no studies have evaluated this association in children. The main goal of this study is to evaluate JHS along with anxiety, somatic and behavioral measures in children to clarify if JHS is associated with any of these variables in this age range. METHODS: A sample of 160 children (74 girls and 86 boys) ranging from 5 to 17 o were recruited from a Child-Adolescent Mental Health clinic to participate in the study. All children underwent a diagnostic interview using the Mini International Neuropsychiatric Interview for Children and Adolescents. Instruments used include the Child Behavior Checklist (CBCL), the Screening Questionnaire to detect Hypermobility (SQ-CH) and the Children Manifested Anxiety Scale (CMAS-R). RESULTS: The prevalence of JHS in this sample was 22%, and this was significantly higher in girls (31%) than in boys (14%) (χ2=6.83; P=.001). The JHS group scored significantly higher in the CMAS-R total anxiety (F=4.51; P=.035), CMAS-R Physiological anxiety (F=7.19; P=.008) and the CBCL somatic complaints (F=8.46; 0.004) and regression analyses showed that these 3 variables were predictors of JHS (χ2=36.77; P<.001; r2=0.22). The JHS group also scored higher in some behavioral measures. CONCLUSION: Children with JHS have higher frequency of anxiety disorders and higher intensity of physiological anxiety, somatic complaints, and therefore, JHS might be used as marker for this anxiety phenotype in youngsters.

Comparison of self-report and clinician-rated schizotypal traits in schizotypal personality disorder and community controls.

Given the common use of self-report questionnaires to assess schizotypy in personality pathology and schizophrenia research, it is important to determine the concordance between self-report and clinician ratings. 250 individuals with schizotypal personality disorder (SPD) and 116 community controls (CTR) were assessed on schizotypal traits using a clinical interview, the Structured Interview for DSM-IV Personality disorders (SIDP), and a self-report questionnaire, the Schizotypal Personality Questionnaire (SPQ). Ordinal logistic regressions examined concordance between self-reported and clinician-rated scores in CTR and SPD separately. Analyses of variance examined how the SPQ performed on differentiating between CTR with low schizotypy, CTR with high schizotypy, and SPD. For both CTR and SPD, higher SPQ subscale scores were significantly associated with higher clinician ratings on the respective SIDP items for the Ideas of Reference, Magical Thinking, Unusual Perceptual Experience, Suspiciousness, and Social Anxiety items, but not the Odd Speech or Limited Affect items. Higher SPQ subscale scores for Odd Behavior and Lack of Close Friends were significantly associated with the clinician-rated SIDP item scores in CTR but not SPD. CTR with low schizotypy scored lower on all SPQ subscales than CTR with high schizotypy, who did not differ from SPD. Self-report ratings are concordant with clinician ratings for positive schizotypal traits, whereas certain disorganization and interpersonal traits are not, particularly for individuals with SPD. The SPQ can differentiate between high and low schizotypy controls, but not between high schizotypy controls and individuals with SPD. Assessment of schizotypal traits should include both self-report questionnaires and clinician ratings.

Both anxiety and joint laxity determine the olfactory features in panic disorder.

Previous research showed a high sensitivity in sensorial modalities in panic disorder (PD). This disorder has been consistently associated to the joint hypermobility syndrome (JHS). In non-clinical samples, this collagen alteration has been also related to an enhanced sensitivity in some sensorial modalities. The main aim of this study is to explore the olfactory functioning in PD in relation to JHS. Sixty patients with PD and sixty healthy controls performed the Sniffin' Sticks Test (SST) (threshold subtest), and completed the Affective Impact of Odors scale (AIO), the Relational Scale of Olfaction (EROL), and the Odor Awareness Scale (OAS). Clinical symptom rating scales and JHS assessment were also obtained. PD patients showed enhanced odor acuity, greater reactivity to smells and also increased odor awareness compared to the healthy controls. Within the patients group, those suffering from JHS displayed higher functioning in all olfactory domains compared to the non-JHS ones. The JHS and anxiety measures emerged as predictor variables of the olfactory function. The present findings highlight the importance of the olfactory function in PD and underline that both, JHS and anxiety, determine the olfactory characteristics in this disorder.

Assessing body awareness and autonomic reactivity: Factor structure and psychometric properties of the Body Perception Questionnaire-Short Form (BPQ-SF).

Body awareness and reactivity dysfunction are characteristic of a range of psychiatric disorders. Although the neural pathways communicating between the body and brain that contribute to these experiences involve the autonomic nervous system, few research tools for studying subjective bodily experiences have been informed by these neural circuits. This paper describes the factor structure, reliability, and convergent validity of the Body Awareness and Autonomic Reactivity subscales of the Body Perception Questionnaire-Short Form (BPQ-SF). Exploratory and confirmatory factor analyses were applied to data from three samples collected via the internet in Spain and the US and a college population in the US (combined n = 1320). Body awareness was described by a single factor. Autonomic reactivity reflected unique factors for organs above and below the diaphragm. Subscales showed strong reliability; converged with validation measures; and differed by age, sex, medication use, and self-reported psychiatric disorder. Post hoc analyses were used to create the 12-item Body Awareness Very Short Form. Results are discussed in relation to the distinct functions of supra- and sub-diaphragmatic autonomic pathways as proposed by the Polyvagal Theory and their potential dysfunction in psychiatric disorders.

The Neurobiology of Borderline Personality Disorder.

This article reviews the most salient neurobiological information available about borderline personality disorder (BPD) and presents a theoretic model for what lies at the heart of BPD that is grounded in those findings. It reviews the heritability, genetics, and the biological models of BPD, including the neurobiology of affective instability, impaired interoception, oxytocin and opiate models of poor attachment or interpersonal dysfunction, and structural brain imaging over the course of development in BPD; and posits that the core characteristic of BPD may be an impairment in emotional interoception or alexithymia.

Olfactory functioning in panic disorder.

BACKGROUND: The olfactory function in panic disorder (PD) has been scarcely approached in the literature. The purpose of this paper is to study this question by focusing on the olfactory sensitivity (i.e. detection threshold), the reactivity to odors, and the odor awareness in patients suffering from PD. METHODS: 41 patients with PD and 41 healthy controls performed Sniffin׳ Sticks Test (threshold subtest) and completed the Affective Impact of Odors scale (AIO), the Relational Scale of Olfaction (EROL) and the Odor Awareness Scale (OAS). Clinical symptoms rating scales were concurrently obtained. RESULTS: PD patients showed lower olfactory detection thresholds (i.e. higher sensitivity) along with an enhanced reactivity to odors as well as a greater olfactory awareness compared to the healthy controls. The severity of PD was significantly associated with the olfactory questionnaires ratings, but not with the detection ability. Olfactory measures were intercorrelated in most cases. LIMITATIONS: i) The results of the olfactory sensitivity are limited to one odorant (phenyl ethyl alcohol) and thus may not be generalizable to other odorants. ii) As comorbid Axis II disorders were not screened, it is not possible to exclude the influence of personality traits in our results. iii) The involvement of the medications in some olfactory outcomes cannot be ruled out. CONCLUSION: The current findings highlight the importance of the olfactory function in PD as patients appeared to be highly sensitive, reactive and aware of odors. These results are discussed in the light of the common neural substrates involved in the olfactory processing and in the pathophysiology of PD, and also related to the clinical features of this disorder.