Linehan’s biosocial model applied to emotion dysregulation in autism: a narrative review of the literature and an illustrative case conceptualization

Emotion dysregulation (ED) is a transdiagnostic difficulty prevalent in autism spectrum condition (ASC). Importantly, recent research has suggested that ED is involved in self-harm and suicidality. Pre-existing models on the etiology of ED in ASC focus mainly on biological factors to ASC features, such as sensory sensitivities, poor flexibility, and sensitivity to change. However, although psychosocial factors seem to play a role in the emergence of ED in ASC as well (e.g., childhood maltreatment and camouflaging), there is a lack of a comprehensive model conceptualizing biosocial factors involved in ED in autistic people. Linehan’s biosocial model (1993) is one of the leading etiological models of ED in borderline personality disorder (BPD). It conceptualizes ED as emerging from transactions between a pre-existing emotional vulnerability in the child and an invalidating developmental environment. Beyond its clinical relevance, Linehan’s model has gathered empirical evidence supporting its pertinence in BPD and in other psychiatric disorders. Although ASC and BPD are two distinct diagnoses, because they may share ED, Linehan’s biosocial model might be useful for understanding the development of ED in ASC. Hence, this article aims to provide an application and extension of Linehan’s model to conceptualize ED in ASC. To do so, we conducted a narrative review of the literature on ED and its underlying factors in ASC from a developmental perspective. To investigate the pertinence of the biosocial model applied to ED in autistic people, we were interested on data on (i) ED and its behavioral correlates in ASC, in relation to the biosocial model, (ii) the potential biological and psychosocial correlates of ED in ASC and (iii) the overlapping difficulties in ASC and BPD. Finally, to assess the pertinence of the model, we applied it to the case of an autistic woman presenting with ED and suicidal behaviors. Our review and application to the case of an autistic woman suggest that ED in ASC encompasses factors related to both biological and psychosocial risk factors as conceptualized in the BPD framework, although in both domains ASC-specific factors might be involved

Disentangling racing thoughts from mind wandering in adult attention deficit hyperactivity disorder

IntroductionMental restlessness reported by adult with Attention Deficit Hyperactivity Disorder (ADHD) has been mainly explained by excessive mind wandering. However, the description of a mind constantly on the go is also akin to racing thoughts, predominantly described in bipolar disorder. This paper aimed at disentangling mind wandering from racing thoughts in adult with ADHD. Associations between those mental phenomena and the ADHD symptomatology were also investigated.MethodsTo this aim, 84 adults with ADHD completed self-reported questionnaires, including the Mind Wandering-Deliberate and Mind Wandering-Spontaneous questionnaires, the Racing and Crowded Thoughts Questionnaire and the Daydreaming Frequency Scale. Factorial analysis and multiple linear regressions were performed.ResultsThe factor analysis yielded a two-factor solution. The first factor encompassed the three facets of racing thoughts and was predicted by emotional lability. The second comprised deliberated-MW, spontaneous-MW and daydreaming, but was neither related to the ADHD symptoms, nor functional impairment.DiscussionThese findings suggest that MW and racing thoughts are two distinguishable mental phenomena. Racing thoughts appear to be a relevant hypothesis to explain the mental restlessness in adult ADHD

Efficacy of Chronic Antidepressant Treatments in a New Model of Extreme Anxiety in Rats

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders

Panique et pandémie : revue de la littérature sur les liens entre le trouble panique et l’épidémie à SARS-CoV-2

Résumé L’état de panique associé à la pandémie liée au SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) incite à s’interroger sur les troubles anxieux que cette situation pourrait générer ou aggraver. Si la littérature a déjà fourni des projections généralistes en la matière, les données concrètes concernent à ce stage davantage le trouble de stress post-traumatique et le trouble obsessionnel compulsif, tandis que quelques évaluations s’intéressent au cadre nosographie du trouble anxieux généralisé. Le trouble panique ne se voit que peu ou pas cité et l’évocation de la « panique », au sens social, la supplante largement. Bien que d’une légitimité clinique encore débattue, le trouble panique qualifié de « respiratoire » pourrait se voir augmenter en nombre et/ou être intensifié chez les patients qui en présentent déjà. D’éventuelles situations co-morbides entre un tel trouble et la COVID-19 (coronavirus disease 2019) doivent inciter à certaines précautions en matière de prescriptions médicamenteuses, notamment en lien avec les traitements ou situations, sources d’hypokaliémie : (i) le salbutamol, source potentielle de surconsommation, notamment chez les patients anxieux ; (ii) l’infection par le SARS-CoV-2 et plus encore en cas de diarrhées et/ou vomissements. L’hypokaliémie est associée à un risque accru de torsade de pointe, il convient donc également d’être prudent en matière de prescription de psychotropes à risque : comme avec le citalopram et l’escitalopram, des antidépresseurs indiqués dans le trouble panique ou encore l’hydroxyzine, à visée anxiolytique. Ces données sont de nature à resituer l’importance de la prise en considération du trouble panique dans le cadre de la pandémie en cours. Although the “panic” word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59–82% and 31–55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence given that some etiological and maintenance factors associated with panic disorder – i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities – are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 epidemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe, thus caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19)

Joint Assessment of Structural, Perfusion, and Diffusion MRI in Alzheimer's Disease and Frontotemporal Dementia

Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4 Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD

Early neuromodulation prevents the development of brain and behavioral abnormalities in a rodent model of schizophrenia

The notion that schizophrenia is a neurodevelopmental disorder in which neuropathologies evolve gradually over the developmental course indicates a potential therapeutic window during which pathophysiological processes may be modified to halt disease progression or reduce its severity. Here we used a neurodevelopmental maternal immune stimulation (MIS) rat model of schizophrenia to test whether early targeted modulatory intervention would affect schizophrenia’s neurodevelopmental course. We applied deep brain stimulation (DBS) or sham stimulation to the medial prefrontal cortex (mPFC) of adolescent MIS rats and respective controls, and investigated its behavioral, biochemical, brain-structural and -metabolic effects in adulthood. We found that mPFC-DBS successfully prevented the emergence of deficits in sensorimotor gating, attentional selectivity and executive function in adulthood, as well as the enlargement of lateral ventricle volumes and mal-development of dopaminergic and serotonergic transmission. These data suggest that the mPFC may be a valuable target for effective preventive treatments. This may have significant translational value, suggesting that targeting the mPFC before the onset of psychosis via less invasive neuromodulation approaches may be a viable preventive strategy.We thank Renate Winter, Doris Zschaber and Roselies Pickert for excellent technical assistance. This research was conducted under the EraNet Neuron framework (DBS_F20rat) and supported by the BMBF, Germany (B01EW1103, 01EE1403A), Fundación Mapfre, Comunidad de Madrid and the Ministry of Economy and Competitiveness ISCIII-FIS grants (PI14/00860, CPII/00005) co-financed by ERDF (FEDER) Funds from the European Commission, ‘A way of making Europe’, Spain (PI14/00860, CPII/00005, MV1500002), the CSO-MOH, Israel (3-8580) and the Canadian Institutes of Health Research, Canada (CIHR, 110068), and co-financed by the DFG, Germany (WI 2140/1-1/2; WI 2140/2-1).Publicad

Actin waves do not boost neurite outgrowth in the early stages of neuron maturation

During neurite development, Actin Waves (AWs) emerge at the neurite base and move up to its tip, causing a transient retraction of the Growth Cone (GC). Many studies have shown that AWs are linked to outbursts of neurite growth and, therefore, contribute to the fast elongation of the nascent axon. Using long term live cell-imaging, we show that AWs do not boost neurite outgrowth and that neurites without AWs can elongate for several hundred microns. Inhibition of Myosin II abolishes the transient GC retraction and strongly modifies the AWs morphology. Super-resolution nanoscopy shows that Myosin IIB shapes the growth cone-like AWs structure and is differently distributed in AWs and GCs. Interestingly, depletion of membrane cholesterol and inhibition of Rho GTPases decrease AWs frequency and velocity. Our results indicate that Myosin IIB, membrane tension, and small Rho GTPases are important players in the regulation of the AW dynamics. Finally, we suggest a role for AWs in maintaining the GCs active during environmental exploration

The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition

Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent