Temperament in trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) and skin picking disorder (SPD) result in significant psychosocial burden. Despite this burden, however, risk factors related to the development of these disorders remain unclear. The present study assessed temperament in a well-characterized sample of adults with TTM or SPD. METHODS: A total of 202 adults age 18 to 65 were enrolled; 44 had TTM, 30 had SPD, and 128 served as controls. Participants completed the self-report Tridimensional Personality Questionnaire (TPQ) to examine the severity of TTM and SPD symptoms, quality of life, and temperament. Group differences were characterized and correlations with other measures were examined. RESULTS: Compared to controls, those with TTM or SPD scored significantly higher on harm avoidance and its subscales, with TTM associated with higher scores than SPD. Those with TTM or SPD scored significantly higher on only 1 measure of novelty seeking (extravagance). Higher TPQ harm avoidance correlated with worse hair pulling severity and worse quality of life. CONCLUSIONS: The temperament traits of participants with TTM or SPD differed in significant ways from controls; those with TTM or SPD generally demonstrated similar trait profiles. A dimensional approach to the personalities of those with TTM or SPD may offer insight and provide clues to treatment strategies.

Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder.

OBJECTIVE: Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior. METHODS: One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking. RESULTS: Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms. CONCLUSIONS: This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.

Clinical Characteristics of Youth with Trichotillomania (Hair-Pulling Disorder) and Excoriation (Skin-Picking) Disorder.

Body-focused repetitive disorders (BFRBDs) are understudied in youth and understanding of their underlying mechanisms is limited. This study evaluated BFRBD clinical characteristics, and two factors commonly implicated in their maintenance - emotion regulation and impulsivity - in 53 youth aged 11 to 17 years: 33 with BFRBDs and 20 controls. Evaluators administered psychiatric diagnostic interviews. Participants rated BFRBD severity, negative affect, quality of life, family functioning, emotion regulation, distress tolerance, and impulsivity. Youth with BFRBDs showed poorer distress tolerance and quality of life, and higher impulsivity and negative affect than controls, with no differences in family impairment. BFRBD distress/impairment, but not BFRBD severity, correlated with anxiety and depression, and poorer distress tolerance. Findings suggest youth with BFRBDs show clinical patterns aligning with prior research; highlight the role of distress tolerance in child BFRBDs; and suggest the utility of acceptance and mindfulness-based therapies for unpleasant emotions in BFRBDs. Continued research should evaluate factors underlying BFRBDs in youth.

Characteristics and treatment seeking in an adult Hispanic population with trichotillomania and skin picking disorder.

This study reports on characteristics of trichotillomania (TTM) and skin picking disorder (SPD) in an international Hispanic sample of adults. The survey was distributed online globally to a Hispanic population with TTM and SPD. 166 Hispanic adults with TTM (n = 127) or SPD (n = 39) reported moderate levels of symptom severity and low or very low quality of life. Anxiety disorders and OCD were common comorbidities. Hispanic adults with TTM and SPD were more impulsive and compulsive compared to non-Hispanic speaking adults (n = 92). Of the 166 subjects, 129 (77.7%) reported previously seeking treatment. When asked about the challenges they faced in seeking help, 67 (40.4%) identified a lack of therapists, psychologists, and psychiatrists who were knowledgeable about these disorders.

Comorbid trichotillomania and attention-deficit hyperactivity disorder in adults.

BACKGROUND: Individuals with trichotillomania (TTM), a disorder characterized by repetitive pulling out of one's own hair, often have co-occurring ADHD, but little is known about this comorbidity. Additionally, there have been intimations in the literature that treatment of ADHD with stimulants may worsen TTM symptoms. This study aims to examine clinical aspects of individuals with TTM and co-occurring ADHD. METHODS: 308 adults with a current diagnosis of TTM were assessed for ADHD using the Mini International Neuropsychiatric Interview 7.0.2 and Adult ADHD Self Report Scale. Participants also completed clinical measures related to TTM severity, impulsivity, quality of life, and psychosocial dysfunction. A series of analyses of variance were used to calculate differences in scale scores among subjects with and without co-occurring ADHD. RESULTS: Of the 308 participants, 47 (15.3%) met the clinical threshold for ADHD. Participants with ADHD reported significantly higher scores in all first and second factor traits of impulsivity, including attentional impulsiveness (p < .0001), motor impulsiveness (p < .0001), and non-planning impulsiveness (p < .0001). Interestingly, participants with ADHD did not report significant differences in TTM severity, perceived quality of life, or functional impairment, regardless of medication status. DISCUSSION: The data suggest that ADHD is common in adults with TTM, and the comorbidity is associated with heightened impulsivity. The co-occurrence of ADHD does not affect individuals' quality of life, symptom severity, or functionality. Taking stimulant medications for ADHD also did not appear to affect TTM severity, despite past case reports suggesting these medications may lead to onset or worsening of TTM.

Cortical dopamine reduces the impact of motivational biases governing automated behaviour.

Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.

Quality of life in trichotillomania: An assessment of specific life domains.

BACKGROUND: The Quality of Life Inventory (QOLI) gauges importance and satisfaction ratings in areas of life such as work, health, and family. An examination of QOLI scores among individuals with trichotillomania (TTM), a hair-pulling disorder, might provide insight on domain-specific interventions to counteract factors that may be contributing to lower quality-of-life (QOL) scores. METHODS: Three hundred thirty-three adults with TTM and 90 healthy controls (age 18 to 65) completed the QOLI and various symptom severity measures. We compared participants with TTM with controls on their overall QOLI scores as well as on QOL subdomains using independent sample t tests with a Bonferroni correction. RESULTS: Participants with TTM had significantly lower overall QOL compared with controls (t [421] = 7.858, P < .001). Additionally, participants with TTM reported significantly lower QOL scores in the following areas of their lives: health, self-esteem, goals and values, play, learning, creativity, helping, love, friends, children, and home (all P < .003). CONCLUSIONS: Lower overall QOL and in specific domains of life highlight the complexity of overall life satisfaction measures in people with TTM. Further research may provide direction on future interventions and insight for family and/or friends supporting individuals with TTM.

Tetrahydrocannabinol fails to reduce hair pulling or skin picking: results of a double-blind, placebo-controlled study of dronabinol.

Body-focused repetitive behaviors (BFRBs) such as trichotillomania and skin picking disorder are associated with decreased self-esteem and poor quality of life. The objective of this study was to evaluate dronabinol, a cannabinoid agonist, for the reduction of BFRB symptoms. Fifty adults with either trichotillomania (n = 34) or skin picking disorder (n = 16) were recruited for a randomized, double-blind, placebo-controlled study. Participants received 10-week treatment with dronabinol (5-15 mg/day) or placebo. The primary efficacy outcome measure was the change on the clinician-rated National Institute of Mental Health scale for hair pulling or skin picking. Both dronabinol and placebo treatment were associated with significant reductions in BFRB symptoms. Dronabinol did not significantly separate from placebo on any efficacy measure. At week 10, 67% of the treatment group were classified as responders (Clinical Global Impressions-Improvement Score of very much or much improved) compared to 50% in the placebo group (P value = 0.459). This study assessed the efficacy of dronabinol, a synthetic form of tetrahydrocannabinol, in the treatment of BFRBs, and found no differences in symptom reductions between dronabinol and placebo.

Parental Bonding in Trichotillomania and Skin Picking Disorder.

BACKGROUND: One means of understanding the effect of environmental factors on psychiatric disorders is by examining perceived parenting behavior in the childhood of individuals with trichotillomania and skin picking disorder (i.e. body focused repetitive behaviors (BFRBs)). We hypothesized that adults with BFRBs would show higher scores on dimensions of "care" and "overprotection". Specifically, we predicted that adults with BFRBs would have parents in the "affectionate constraint" quadrant, based on a combination of high care and high protection scores. METHODS: We assessed demographic and clinical differences in 184 adults between the ages of 18 and 65 with Trichotillomania (TTM) (n = 43) and Skin Picking Disorder (SPD) (n = 75), and both (n = 66). The Parental Bonding Instrument (PBI) measured "care" and "overprotection" items. Results from the PBI were compared across groups and with normal control data using independent sample t-tests. RESULTS: Individuals in the BFRB group had significantly lower maternal and paternal care scores compared to controls. The TTM, SPD, and TTM + SPD (combined) groups all had lower maternal care scores than controls. The TTM + SPD (combined) group had significantly lower paternal care scores and higher maternal protection scores than the normative averages. The most common parenting patterns in subjects with BFRBs were maternal and paternal affectionless control (low care/high protection). From our sample, only 27 % reported optimal maternal parenting and 28 % reported optimal paternal parenting. DISCUSSION: These preliminary data suggest that low maternal and paternal care may be associated with BFRBs. However, the nature of this relationship should be further explored, as these results do not necessarily mean that affectionless control parenting leads to a predisposition to BFRBs, and there may in fact be other environmental factors at play. Identifying how individuals perceive familial relationships may provide direction for clinicians in developing tools to address the burden caused by BFRBs.

Nutrition in Skin Picking Disorder and Trichotillomania.

Objective: Excessive calorie intake constitutes a global public health concern, due to its associated range of untoward outcomes. Impulsivity and compulsivity have been linked to dietary intake. However, nothing is known about dietary intake and body-focused repetitive behaviors, despite their classification as obsessive-compulsive related conditions, and high co-morbidity with impulsive and compulsive conditions. Methods: One hundred and ninety six adults with trichotillomania or skin picking disorder were recruited. Dietary intake over the preceding year was quantified using the Dietary Fat and Free Sugar Short questionnaire. Relationships between dietary fat/sugar intake and behaviors were evaluated using regression modeling. Results: Sugar intake was significantly related to higher trans-diagnostic compulsivity (p = 0.011) and higher non-planning impulsivity (p = 0.013) In terms of saturated fat intake, there was no significant relationship to the explanatory variables. A combination high fat/high sugar diet was significantly associated with higher motor impulsivity (p = 0.005). Conclusions: Past-year nutrition appears to be significantly associated with trans-diagnostic impulsivity and compulsivity. The role of poor nutrition in these disorders and related conditions, and its link with impulsivity and compulsivity, requires longitudinal research attention; and clinical work should address not only psychiatric symptoms but also impact of lifestyle of overall health.

Clinical presentation of body-focused repetitive behaviors in minority ethnic groups.

BACKGROUND: Body-focused repetitive behaviors (BFRBs), such as trichotillomania and skin picking disorder, are psychiatric disorders characterized by repetitive grooming that result in hair loss or excoriations. Questions remain as to whether there are racial/ethnic differences in the clinical presentation of BFRBs. METHODS: We recruited 539 adults with DSM-5 trichotillomania or skin picking disorder. Of these, 76 (14.1%) self-identified as Black, Asian, or Minority Ethnic (BAME), while 463 (85.9%) self-identified as white Caucasian (hereafter referred to as non-BAME). BAME and non-BAME participants were compared on demographics, symptom severity, comorbid conditions and psychosocial impairment. RESULTS: Groups did not differ in terms of age, sex, or education levels. BAME individuals reported significantly more time spent picking or hair pulling per day compared to non-BAME individuals, and were less likely to have received treatment for their BFRB symptoms. Some differences were also found with respect to where on the body people pull and pick from. DISCUSSION: In general, the clinical profiles of BFRBs appeared similar between those from BAME versus non-BAME backgrounds. However, differences were found in terms of treatments received and an aspect of symptom severity. The findings highlight the need to better understand the heterogeneity of BFRBs including potential health inequalities.

Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.

Despite the availability of evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them. Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Conduct a proof of concept study to examine whether a COMT inhibitor would reduce OCD symptoms to a greater extent than placebo. We conducted a randomized, placebo-controlled, double-blind crossover trial in adults with OCD (N = 20). Participants were assessed at baseline, after 2 weeks of tolcapone, and again after 2 weeks of placebo on measures of OCD symptom severity and psychosocial functioning. There was a 1-week washout period between the 2-week treatment phases. Two weeks of tolcapone was associated with significant improvement in OCD versus two weeks of placebo (t = 2.194, P = 0.0409). The mean percentage decreases in the total Yale-Brown obsessive-compulsive scale (YBOCS) scores for the entire sample over the corresponding 2-week period were 16.4% for tolcapone and 3.6% for placebo. These data indicate that brain penetrant COMT inhibitors merit further investigation as a candidate new treatment for OCD.

Sleep quality and its clinical associations in trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) is characterized by recurrent hair pulling and associated hair loss. Skin picking disorder (SPD) is characterized by recurrent skin picking and associated scarring or tissue damage. Both disorders are also accompanied by psychological distress and poor sleep. Very little, however, is known about lifestyle variables that may contribute to symptom severity in these disorders. METHODS: We recruited 87 adults as part of a cross-sectional study of 3 groups (TTM, SPD, and non-affected). Clinical subjects (n=69) were compared with controls (n=18) on sleep quality as measured by Pittsburgh Sleep Quality Index (PSQI). We used partial least squares regression to identify which variables were significantly associated with poor sleep quality among those participants with TTM or SPD. RESULTS: Clinical subjects had significantly poorer sleep quality than controls. Sleep quality was significantly related to older age, worse perceived stress, lower distress tolerance and greater impulsivity in adults with BFRBs. Poor sleep quality was associated with worse hair pulling symptom severity but not skin picking severity. Higher levels of comorbid mental disorders was also associated with worse sleep, above and beyond the impact of these other variables. CONCLSUIONS: Poor sleep quality appears to be related to multiple variables. Further research is needed to determine causality and to tailor treatment to specific patient needs.

A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder.

BACKGROUND: Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals. AIMS: To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms. METHOD: Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models. RESULTS: There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo. CONCLUSIONS: Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.

Problematic Internet use (PIU), personality profiles and emotion dysregulation in a cohort of young adults: trajectories from risky behaviors to addiction.

Problematic Internet Use (PIU) encloses excessive online activities (like video gaming, social media use, web-streaming, pornography viewing, buying). Despite its psychological burden, risk factors related to PIU remain still unclear. In the present study we explored the role of personality traits and emotion dysregulation as potential vulnerability factors for PIU. In a sample of American young adults with different PIU risk levels (established through the Internet Addiction Diagnostic Questionnaire), we administered the Tridimensional Personality Questionnaire (TPQ), the Difficulties in Emotion Regulation Scale (DERS), the Barratt Impulsiveness Scale, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale. PIU participants were more likely to report lower TPQ scores in novelty seeking, harm avoidance and reward dependence. Moreover, DERS total scores significantly differed across PIU-risk groups, along with a progressively higher occurrence of depression, anxiety and impulsivity. These results preliminarily support the hypothesis of PIU as a mainly behavior aimed at 'escaping' from negative affects. Besides confirming the role of some personality traits and emotional dysregulation, we propose the concept of risk-trajectories to monitor and prevent the emergence of PIU. Gaining more insight into PIU vulnerability factors may allow us to establish targeted interventions to cope with emotion dysregulation and negative affects.

Problematic internet use: an exploration of associations between cognition and COMT rs4818, rs4680 haplotypes.

OBJECTIVE: Problematic internet users suffer from impairment in a variety of cognitive domains. Research suggests that COMT haplotypes exert differential effects on cognition. We sought to investigate differences in the genetic profiles of problematic internet users and whether those could shed light on potential cognitive differences. METHODS: We recruited 206 non-treatment seeking participants with heightened impulsive traits and obtained cross-sectional demographic, clinical, and cognitive data as well as the genetic haplotypes of COMT rs4680 and rs4818. We identified 24 participants who presented with problematic internet use (PIU) and compared PIU and non-PIU participants using one-way analysis of variance (ANOVA) and chi square as appropriate. RESULTS: PIU was associated with worse performance on decision making, rapid visual processing, and spatial working memory tasks. Genetic variants were associated with altered cognitive performance, but rates of PIU did not statistically differ for particular haplotypes of COMT. CONCLUSION: This study indicates that PIU is characterized by deficits in decision making and working memory domains; it also provides evidence for elevated impulsive responses and impaired target detection on a sustained attention task, which is a novel area worth exploring further in future work. The effects observed in the genetic influences on cognition of PIU subjects imply that the genetic heritable components of PIU may not lie within the genetic loci influencing COMT function and cognitive performance; or that the genetic component in PIU involves many genetic polymorphisms each conferring only a small effect.

Peripheral versus central nervous system APOE in Alzheimer's disease: Interplay across the blood-brain barrier.

The apolipoprotein E (APOE) ε4 allele has been demonstrated as the preeminent genetic risk factor for late onset Alzheimer's disease (AD), which comprises greater than 90% of all AD cases. The discovery of the connection between different APOE genotypes and AD risk in the early 1990s spurred three decades of intense and comprehensive research into the function of APOE in the normal and diseased brain. The importance of APOE in the periphery has been well established, due to its pivotal role in maintaining cholesterol homeostasis and cardiovascular health. The influence of vascular factors on brain function and AD risk has been extensively studied in recent years. As a major apolipoprotein regulating multiple molecular pathways beyond its canonical lipid-related functions in the periphery and the central nervous system, APOE represents a critical link between the two compartments, and may influence AD risk from both sides of the blood-brain barrier. This review discusses recent advances in understanding the different functions of APOE in the periphery and in the brain, and highlights several promising APOE-targeted therapeutic strategies for AD.

A double-blind, placebo-controlled study of vortioxetine in the treatment of binge-eating disorder.

BACKGROUND: Binge-eating disorder (BED) is associated with impaired quality of life and has a number of untoward public health associations. There are few established pharmacological treatments for BED, and available options are not suitable for all individuals. Vortioxetine is a recently developed pharmacological agent with effects on the serotonergic but also other neurochemical systems, which has yet to be evaluated in this context. METHOD: Eighty adults with BED were recruited for a double-blind, placebo-controlled study. Participants received 12-week treatment with vortioxetine (10 mg/day for 1 week, then increasing to 20 mg/day) or placebo in a parallel design. The primary efficacy outcome measures were binge-eating frequency and weight. Safety data were collected. Effects of active versus placebo treatment were characterized using linear repeated measures models. RESULTS: Both vortioxetine and placebo treatment were associated with significant reductions in binge-eating frequency. Vortioxetine did not differentiate significantly from placebo on any efficacy measure. Frequency of adverse events did not differ between groups. DISCUSSION: Vortioxetine was not more effective than placebo in the treatment of BED. The ability to detect pharmacological treatment benefit may have been hindered by the relatively high placebo response and drop out. Future work should seek to better understand and predict placebo response in BED, with a view to more targeted treatment interventions and, potentially, sample enrichment.

High-density lipoprotein mimetic peptide 4F mitigates amyloid-ß-induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia.

The apolipoprotein E (apoE) ε4 allele is the primary genetic risk factor for late-onset Alzheimer's disease (AD). ApoE in the brain is produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high-density lipoprotein (HDL)-like particles. Accumulation of amyloid-ß protein (Aß) in the brain is a key hallmark of AD, and is thought to initiate a pathogenic cascade leading to neurodegeneration and dementia. The level and lipidation state of apoE affect Aß aggregation and clearance pathways. Elevated levels of plasma HDL are associated with lower risk and severity of AD; the underlying mechanisms, however, have not been fully elucidated. This study was designed to investigate the impact of an HDL mimetic peptide, 4F, on the secretion and lipidation of apoE. We found that 4F significantly increases apoE secretion and lipidation in primary human astrocytes as well as in primary mouse astrocytes and microglia. Aggregated Aß inhibits glial apoE secretion and lipidation, causing accumulation of intracellular apoE, an effect that is counteracted by co-treatment with 4F. Pharmacological and gene editing approaches show that 4F mediates its effects partially through the secretory pathway from the endoplasmic reticulum to the Golgi apparatus and requires the lipid transporter ATP-binding cassette transporter A1. We conclude that the HDL mimetic peptide 4F promotes glial apoE secretion and lipidation and mitigates the detrimental effects of Aß on proper cellular trafficking and functionality of apoE. These findings suggest that treatment with such an HDL mimetic peptide may provide therapeutic benefit in AD. Read the Editorial Highlight for this article on page 580.