DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.

Characterization of affective lability across subgroups of psychosis spectrum disorders

Background Affective lability is elevated and associated with increased clinical burden in psychosis spectrum disorders. The extent to which the level, structure and dispersion of affective lability varies between the specific disorders included in the psychosis spectrum is however unclear. To have potential value as a treatment target, further characterization of affective lability in these populations is necessary. The main aim of our study was to investigate differences in the architecture of affective lability in different psychosis spectrum disorders, and if putative differences remained when we controlled for current symptom status. Methods Affective lability was measured with The Affective Lability Scale Short Form (ALS-SF) in participants with schizophrenia (SZ, n = 76), bipolar I disorder (BD-I, n = 105), bipolar II disorder (BD-II, n = 68) and a mixed psychosis-affective group (MP, n = 48). Multiple analyses of covariance were conducted to compare the ALS-SF total and subdimension scores of the diagnostic groups, correcting for current psychotic, affective and anxiety symptoms, substance use and sex. Double generalized linear models were performed to compare the dispersion of affective lability in the different groups. Results Overall group differences in affective lability remained significant after adjusting for covariates (p = .001). BD-II had higher affective lability compared to SZ and BD-I (p = .004), with no significant differences between SZ and BD-I. There were no significant differences in the contributions of ALS-SF dimensions to the total affective lability or in dispersion of affective lability between the groups. Conclusions This study provides the construct of affective lability in psychosis spectrum disorders with more granular details that may have implications for research and clinical care. It demonstrates that despite overlap in core symptom profiles, BD-I is more similar to SZ than it is to BD-II concerning affective lability and the BD groups should consequently be studied apart. Further, affective lability appears to be characterized by fluctuations between depressive- and other affective states across different psychosis spectrum disorders, indicating that affective lability may be related to internalizing problems in these disorders. Finally, although the level varies between groups, affective lability is evenly spread and not driven by extremes across psychosis spectrum disorders and should be assessed irrespective of diagnosis.

Conditioned hallucinations and prior hyper-precision are state-sensitive markers of hallucination susceptibility

Recent advances in computational psychiatry have identified latent cognitive and perceptual states that predispose to psychotic symptoms. Behavioral data fit to Bayesian models have demonstrated an over-reliance on priors during perception in select samples of individuals with hallucinations. However, the clinical utility of this observation depends on whether it reflects static symptom risk or current symptom state. To determine whether task performance and estimated prior weighting related to specific elements of symptom expression, a large, heterogeneous, and deeply-phenotyped sample of hallucinators (N = 249) and non-hallucinators (N=209) performed the Conditioned Hallucination (CH) task. CH rates were sensitive to hallucination state, correlating with hallucination severity measures over the two days leading up to task completion and driven by heightened reliance on past experiences (priors). To further test this relationship, a subset of AH+ participants (N = 40) performed a repeated-measures version of the CH task. Changes in both CH frequency and relative prior precision varied with changes in AH frequency on follow-up. These results support the use of CH rate and prior hyper-precision as state markers of hallucination status, potentially useful in tracking disease development and treatment response.

Investigating the Transdiagnostic Value of Subjective Emptiness

It is common for people with mental health problems to report feelings of emptiness. However, the association of subjective emptiness with specific disorders and its unique role within dimensional taxonomies of personality pathology is not well understood. The present study assesses the transdiagnostic value of subjective emptiness using a recently developed self-report measure in a mixed sample of 157 participants. The authors investigated the associations of emptiness with clinically relevant variables, including borderline personality disorder symptoms, depression, anxiety, suicidal ideation, and suicide attempts. Subjective emptiness showed strong positive relationships with all criteria. Regression models controlling for impairments of personality functioning, maladaptive personality traits, and current symptom distress supported the incremental validity of emptiness for specific disorder constructs and suicidality. These findings indicate that emptiness represents a facet of psychopathology that can be particularly useful for the classification of mental disorders, and in particular internalizing disorders involving self-dysfunction and detachment.

Examining The Effectiveness Of Psychotherapy Provided At A Canadian University Counselling Centre : Prelimary Results

Psychotherapy is an effective treatment for a variety of mental illnesses. Despite this evidence, the average Canadian does not have access to psychotherapy because Medicare does not generally cover the costs. However, Canadians attending post-secondary education can generally access psychotherapy at no direct cost. Currently, there is limited Canadian research on the effectiveness of psychotherapy provided at university counselling centres (UCCs). The present study examined the effectiveness of individual counselling provided at a Toronto university counselling centre and the preliminary results are presented. Participants experienced a statistically significant decrease in mental health-related symptoms as measured by the Outcome Questionnaire 45.2 (OQ-45), overall current symptom severity, and severity of symptom interference in daily life from pre- to post-counselling. Current medication, supplement, and vitamin use and family social support were not significant predictors of OQ-45 score changes. Participants also gave general feedback indication that counselling was effective and beneficial.

Examining The Effectiveness Of Psychotherapy Provided At A Canadian University Counselling Centre : Prelimary Results

Psychotherapy is an effective treatment for a variety of mental illnesses. Despite this evidence, the average Canadian does not have access to psychotherapy because Medicare does not generally cover the costs. However, Canadians attending post-secondary education can generally access psychotherapy at no direct cost. Currently, there is limited Canadian research on the effectiveness of psychotherapy provided at university counselling centres (UCCs). The present study examined the effectiveness of individual counselling provided at a Toronto university counselling centre and the preliminary results are presented. Participants experienced a statistically significant decrease in mental health-related symptoms as measured by the Outcome Questionnaire 45.2 (OQ-45), overall current symptom severity, and severity of symptom interference in daily life from pre- to post-counselling. Current medication, supplement, and vitamin use and family social support were not significant predictors of OQ-45 score changes. Participants also gave general feedback indication that counselling was effective and beneficial.

REHABILITATION AND MODULATION AIMED AT AMELIORATING AWARENESS IN ANOSOGNOSIA FOR HEMIPLEGIA

Anosognosia for hemiplegia is a multifaceted syndrome that has a detrimental impact on the patient. Various theories based on behavioural and neuroanatomical data have been proposed to explain the mechanisms underlying the symptoms. These approaches have resulted in the development of a number of different proce- dures aimed at reducing symptoms or enhancing residual aware- ness. The article reviews rehabilitation attempts and their effects on individual cases and groups of patients. A selection of material was made using indexed articles published between 1987 and 2019. The inclusion criteria were: i) the presence of a neuropsychological assessment and ii) the presence of one or more methods specifically used to reduce AHP symptoms, or to enhance residual forms of awareness. The review indicates that intervention procedures have moved from bottom-up to more cognitive and metacognitive approaches. In fact, initially anosognosia for hemiplegia was considered to be a co-oc- current symptom of other neuropsychological conditions (e.g. spa- tial neglect) and interventions were borrowed from the rehabilitation techniques that had had success in relieving these other disorders. When anosognosia was identified as an independent syndrome and residual forms of awareness were demonstrated, procedures attempting to modulate awareness started to focus on specific components of the disease, such as visual perspective, motor monitoring and the updating of beliefs. Although further research is needed in this field, the most recent approaches seem to give more stable, lasting results than earlier methods. A timeline for interventions relating to anosognosia is suggested, and ethical issues are also discussed.

Investigating the Transdiagnostic Value of Subjective Emptiness

It is common for people with mental health problems to report feelings of emptiness. However, the association of subjective emptiness with specific disorders and its unique role within dimensional taxonomies of personality pathology is not well understood. The present study assesses the transdiagnostic value of subjective emptiness using a recently developed self-report measure in a mixed sample of 157 participants. The authors investigated the associations of emptiness with clinically relevant variables, including borderline personality disorder symptoms, depression, anxiety, suicidal ideation, and suicide attempts. Subjective emptiness showed strong positive relationships with all criteria. Regression models controlling for impairments of personality functioning, maladaptive personality traits, and current symptom distress supported the incremental validity of emptiness for specific disorder constructs and suicidality. These findings indicate that emptiness represents a facet of psychopathology that can be particularly useful for the classification of mental disorders, and in particular internalizing disorders involving self-dysfunction and detachment.

Optimal Management of the Hyperkinetic Gallbladder: A Comparison of Outcomes Between Operative and Nonoperative Approaches

Background A hyperkinetic gallbladder is defined as a hepatobiliary iminodiacetic acid (HIDA) scan ejection fraction (EF) of >80%. This condition is poorly described, and there is no current consensus on optimal management. The intent of this study was to determine if cholecystectomy improves symptoms in patients with a hyperkinetic gallbladder when compared to those managed nonoperatively and if there were variables predictive of symptom improvement with or without cholecystectomy. Materials and Methods This retrospective study included patients from 3 academic hospitals in the Atlanta metro area between the years 2006 and 2018. All patients with an EF >80% were included. Following voluntary exclusion patients were contacted by phone. Each patient was administered a questionnaire regarding their surgical history, medical management, and current symptom profile via Otago score. Institutional Institutional Review Board approval was obtained. Results 4785 HIDA scans were performed, and 194 reported an EF >80% (incidence 15.7%). 96% of these scans were reported as normal by the radiologist. 68 patients were able to be contacted by phone and completed the questionnaire. 18 patients underwent cholecystectomy, and 89% reported that their symptoms attributed to gallbladder disease were no longer present. 50 patients did not undergo cholecystectomy, and alternate diagnoses, medication prescriptions, diet modification, emergency department visits, and Otago score were higher in this cohort. Discussion Patients who undergo cholecystectomy for a diagnosis of hyperkinetic gallbladder, on average, report improvement in symptoms when compared to patients managed nonoperatively. This study supports the practice of reporting and managing hyperkinetic gallbladders as a pathologic entity.