Effects of glabellar botulinum toxin injections on resting-state functional connectivity in borderline personality disorder.

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect.

Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study.

Persistent Genital Arousal Disorder (PGAD) is a rare condition-mostly in women-where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops.

Increased functional connectivity in the right dorsal auditory stream after a full year of piano training in healthy older adults.

Learning to play an instrument at an advanced age may help to counteract or slow down age-related cognitive decline. However, studies investigating the neural underpinnings of these effects are still scarce. One way to investigate the effects of brain plasticity is using resting-state functional connectivity (FC). The current study compared the effects of learning to play the piano (PP) against participating in music listening/musical culture (MC) lessons on FC in 109 healthy older adults. Participants underwent resting-state functional magnetic resonance imaging at three time points: at baseline, and after 6 and 12 months of interventions. Analyses revealed piano training-specific FC changes after 12 months of training. These include FC increase between right Heschl's gyrus (HG), and other right dorsal auditory stream regions. In addition, PP showed an increased anticorrelation between right HG and dorsal posterior cingulate cortex and FC increase between the right motor hand area and a bilateral network of predominantly motor-related brain regions, which positively correlated with fine motor dexterity improvements. We suggest to interpret those results as increased network efficiency for auditory-motor integration. The fact that functional neuroplasticity can be induced by piano training in healthy older adults opens new pathways to countervail age related decline.

Alterations in voxel based morphometry and resting state functional connectivity in men with compulsive sexual behavior disorder in the Sex@Brain study.

Aim: Compulsive Sexual Behavior Disorder (CSBD) is a new category in ICD-11. Research examining underlying brain mechanisms is sparse. Research into neurobiological differences can be helpful in advancing the possibilities of new diagnostic approaches and therapeutic methods. The present study aimed to examine brain matter volume and resting state functional connectivity (rs-FC) in CSBD. Methods: Structural and rs-FC magnetic resonance imaging and data from questionnaires were collected in 30 men with CSBD and 32 age- and education-matched controls. Whole brain voxel based morphometry (VBM) and seed based rs-FC in a-priori defined seeds were analyzed. Results: Structural analyses showed that men with CSBD had significantly increased gray matter volume in the right cerebellum, middle occipital and superior frontal lobe. No differences in rs-FC could be detected when using these brain structures as seed regions in rs-FC. In contrast, literature based rs-FC analysis revealed decreased rs-FC between the right orbital middle frontal cortex (mOFC) and the right gyrus rectus, as well as between left pallidum and right post/precentral gyrus in men with CSBD. In the left amygdala we observed increased rs-FC with precuneus in this group. In addition, most of these measures correlated with symptom severity. Conclusion: Structural findings may underscore the idea that the cerebellum plays an important role in sexual arousal and CSBD. Perhaps, a simultaneous activation of the left amygdala and the precuneus reflects a constant sexual occupation of men with CSBD. Furthermore, lower connectivity between mOFC and gyrus rectus in CSBD may support the assumption that sexual stimuli are evaluated more positively because inhibition is decreased.

Personality dimensions of compulsive sexual behavior in the Sex@Brain study.

Background and aims: Hypersexual disorder is characterized by recurrent and intense sexual fantasies, sexual urges, or sexual behaviors that can lead to clinically relevant levels of distress and adverse consequences for affected individuals. Earlier research has established a connection between sexual phenomena, such as compulsive sexual behavior, and personality features. The aim of the present study was to gain further insights into the associations of personality maladjustment and HD. Methods: The present study applied the dimensional approach of personality maladjustment presented in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to connect compulsive sexual behavior to personality maladjustment. We investigated 47 men suffering from HD (age: M = 36.51, SD = 11.47) and 38 matched men without HD (age: M = 37.92, SD = 12.33) regarding personality maladjustment using a 100-item version of the Personality Inventory for DSM-5 (PID-5-BF). Results: The men with HD showed higher levels of personality maladjustment regarding all PID-5-BF domains (negative affect, detachment, psychoticism, antagonism, and disinhibition) and significantly differentiated from men without HD in the level of subordinate facets. However, no domain of personality differentiated significantly between groups using a binary stepwise logistic regression analysis. Discussion and conclusions: In sum, the findings of the study underline the extent of personality maladjustment in men with HD. Interpersonal difficulties which men with HD frequently experience can contribute to clinically relevant levels of distress and adverse consequences reported by affected individuals.

Botulinum Toxin Therapy for Psychiatric Disorders in Clinical Practice: A Retrospective Case Study.

Inhibiting the facial expression of negative emotions via botulinum toxin A (BTX) has been shown to mitigate symptoms of clinical depression in randomized controlled trials. This retrospective case study sought to reproduce the beneficial effects of BTX in a naturalistic setting for major depressive disorder and collect casuistic data on its effect on other mental disorders. Moreover, we describe symptom development across multiple treatment cycles with BTX, and assess the implementation of additional injection targets in the lower face region. Participants were N = 51 adult psychiatric outpatients mainly seeking treatment for depression. Over 50% suffered from comorbid psychiatric conditions, predominantly generalized anxiety disorder (GAD) or borderline personality disorder (BPD). A pre-post case series design was adapted. All participants received BTX-injections in the glabellar region on at least one occasion. Some received additional injections in the mouth region and over multiple treatment cycles. Treatment response was followed up by self-rated scales at varying time intervals post treatment. The results showed that BTX may yield favorable outcomes across multiple and comorbid mental disorders, especially, however, for patients suffering from depression. It potentially prevents the recurrence of clinical symptoms if applied regularly. Adding additional regions of the face does not seem to be superior over applying it to the glabellar region alone. The results add to the growing evidence that BTX therapy is effective in alleviating symptoms of depression. Positive effects can be sustained and reinstated, when applied over multiple treatment cycles. Observed symptom reduction in other psychiatric disorders was less pronounced. Further research is needed to understand the mechanisms by which BTX therapy reduces psychiatric symptoms.

Fine motor control improves in older adults after 1 year of piano lessons: Analysis of individual development and its coupling with cognition and brain structure.

Musical training can improve fine motor skills and cognitive abilities and induce macrostructural brain changes. However, it is not clear whether the changes in motor skills occur simultaneously with changes in cognitive and neurophysiological parameters. In this study, 156 healthy, musically naïve and right-handed older adults were recruited and randomly assigned to a piano training or a music listening group. Before, after 6 and 12 months, participants were scanned using MRI and assessed for fine motor skills, auditory working memory and processing speed. A Bayesian multilevel modelling approach was used to examine behavioural and neurophysiological group differences. The relationships between motor and cognitive and between motor and neurophysiological parameters were determined using latent change score models. Compared with music listening, practicing piano resulted in greater improvement in fine motor skills and probably working memory. Only in the piano group, unimanual fine motor skills and grey matter volume of the contralateral M1 changed together during the 6-12-month period. Additionally, M1 co-developed with ipsilateral putamen and thalamus. Playing piano induced more prevalent coupling between the motor and cognitive domains. However, there is little evidence that fine motor control develops concurrently with cognitive functions. Playing an instrument promotes motor, cognitive and neural development into older age. During the learning process, the consolidation of piano skills appears to take place in sensorimotor networks, enabling musicians to perform untrained motor tasks with higher acuity. Relationships between the development of motor acuity and cognition were bidirectional and can be explained by a common cause as well as by shared resources with compensatory mechanisms.

Determinants of severe QTc prolongation in a real-world gerontopsychiatric setting.

Introduction: QTc prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QTc interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QTc prolongation in gerontopsychiatric patients. Methods: Electrocardiograms of patients on a gerontopsychiatric ward were screened for QTc prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ. Results: The overall prevalence of QTc prolongation was 13.6%, with 1.9% displaying severe QTc prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QTc prolongation were identified; however, patients with severe QTc prolongation tended to take more drugs (p = 0.063). 92.7% of patients with QTc prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QTc prolongation, particularly cardiac diseases. Conclusion: In addition to the use of potentially QTc-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QTc prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QTc prolongation were rare, potentially QTc-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit-risk analyses prior to the initiation of potentially QTc-prolonging drugs and to closely monitor their clinical (side) effects.

Neural correlates of the attention training technique as used in metacognitive therapy - A randomized sham-controlled fMRI study in healthy volunteers.

Introduction: The Attention Training Technique (ATT) developed as part of metacognitive therapy is a psychotherapeutic treatment method used to enhance top-down attentional flexibility and control. This study investigated potential neurocognitive changes due to ATT and its underlying neural mechanisms using pre-to-post functional magnetic resonance imaging (fMRI). Materials and methods: Fifty-four healthy participants were subjected to a randomized, sham-controlled attention training and evaluated using a neurocognitive test battery that partly took place in an fMRI environment. Participants received two doses ATT or sham ATT daily for 1 week. On day eight, all subjects completed the neurocognitive test battery again. Results: After the training, the ATT group showed a significant improvement in reaction times regarding attentional disengagement compared to the sham ATT group. fMRI data showed decreased levels of activation in the anterior cingulate cortex (ACC) when comparing the ATT group to the sham ATT group during attentional disengagement post intervention. No ATT > sham ATT effects were found regarding selective auditory attention, working memory performance and inhibitory control. Discussion: These findings putatively indicate that ATT facilitates faster attention allocation and increased attentional flexibility in healthy subjects. The fMRI results suggest this ATT-dependent improvement is accompanied by reduced ACC activity, indicating a more flexible attentional state.

The androgen system across the menstrual cycle: Hormonal, (epi-)genetic and psychometric alterations.

The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studies investigated alterations of these parameters throughout the menstrual cycle and there is a lack of studies exploring a link towards epigenetic and genetic regulation. This multisite longitudinal study examines behavioral parameters including affectivity, stress perception and various diary parameters of mental and physical well-being in conjunction with testosterone and LH plasma levels in 87 menstruating women. Additionally, Cysteine-Adenenine-Guanin (CAG) repeat length and methylation of the androgen receptor gene collected at four time points across two cycles comprising the menstrual, pre-ovulatory, mid-luteal and premenstrual phase were assesed. There was a significant increase of LH and testosterone plasma levels during the pre-ovulatory phase as well as a decrease of methylation of the androgen receptor at mid-luteal phase. Subjective ratings of physical condition and sexual interest peaked during the pre-ovulatory phase and the former correlated negatively with the androgen receptor gene methylation level. This longitudinal study shows alterations of the androgen system including epigenetic measurements throughout the menstrual cycle. While a link between peripheral testosterone and sexual activity and between increased physical condition and an upregulation of testosterone receptor protein expression can be assumed, the majority of parameters remained unchanged. These initial findings need validation by subsequent studies.

Hypothalamic volume in pedophilia with or without child sexual offense.

The hypothalamus regulates sexual behavior and is simultaneously associated with aggression and violence. Consequently, this brain region is relevant in research of pedophilia and child sexual offenses (CSO). The distinction between these two phenomena is of great importance and was the object of consideration of this study. We analyzed exclusively men, including 73 pedophilic offenders who committed CSO, an equal number of people with pedophilia but without such offenses, and 133 non-pedophilic, non-offending subjects who formed the control group. All data were collected in a multicenter in vivo study and analyzed using a semi-automated segmentation algorithm for 3-Tesla magnetic resonance images. Men with pedophilia who committed CSO on average had a 47 mm3 smaller hypothalamus per side than people without committed CSO. This effect was driven by both the group of non-offending people with pedophilia and the control group. By contrast, the exploratory comparison of pedophilic persons without CSO with the control group showed no significant difference. The present study demonstrates a deviant hypothalamic structure as a neurobiological correlate of CSO in pedophiles, but not in people with pedophilia who have not committed CSO. Thus, it strengthens the argument to distinguish between sexual offending and paraphilic sexual preferences.

Potentially inappropriate prescriptions of antibiotics in geriatric psychiatry-a retrospective cohort study.

Introduction: Older patients are frequently affected by infectious diseases and adverse drug reactions (ADRs) of consecutively prescribed antibiotics. Particularly within geriatric psychiatry, high rates of potentially inappropriate prescriptions (PIPs) have been described, significantly complicating pharmacological treatment. Therefore, this study aimed to investigate the frequency and characteristics of antibiotic PIPs in geriatric psychiatry. Methods: Medication charts of 139 patient cases (mean age 78.8 years; 69.8% female) receiving antibiotic treatment on a geriatric psychiatric ward were analyzed. Utilizing previously published definitions of antibiotic PIPs, adequacy of the antibiotic prescriptions was subsequently assessed. Results: 16.3% of all screened patient cases (139/851) received an antibiotic treatment during their inpatient stay. 59.5% of antibiotic prescriptions were due to urinary tract infections, followed by pulmonary (13.3%) and skin and soft tissue infections (11.3%). 46.7% of all antibiotic prescriptions fulfilled at least one PIP criterium, with the prescription of an antibiotic course for more than seven days as the most common PIP (15.3%). Discussion: Antibiotic PIPs can be considered as a frequent phenomenon in geriatric psychiatry. Especially the use of fluoroquinolones and cephalosporins should be discussed critically due to their extensive side effect profiles. Due to the special characteristics of geriatric psychiatric patients, international guidelines on the use of antibiotics should consider frailty and psychotropic polypharmacy of this patient population more closely.

How the COVID-19 pandemic divides society: Towards a better understanding of differences between supporters and opponents of the COVID-19 pandemic lockdown in Germany.

Implemented COVID-19 containment measures have been fiercely discussed in Germany and corona-related protests have emerged. We assessed mental health in response to the lockdown in Germany and aimed at detecting factors differentiating opponents and supporters of the COVID-19 containment measures. Using a cross-sectional online survey (n = 1219) with a mixed-methods approach, we found increased levels of anxiety and depressive symptoms (PHQ-4 and GAD-7), overall lower well-being (WHO-5), worsened sleep, increased prevalence of interpersonal violence (5.2%) as well as more pronounced irritability including anger and aggression compared to pre-COVID-19 times for all participants. Moreover, opponents demonstrated a more pronounced mental burden with more depression and anxiety, more anger and coping difficulties compared to supporters. In line with previous research, we found opponents to be well-educated, financially stable and strongly estranged by their political institutions. Additionally, applying regression analysis, we found anxiety and negative self-concept to differentiate between opponents and supporters of the COVID-19 pandemic lockdown. Qualitative data confirms an increase in mental burden. Taken together, we identify a more vulnerable group opposing COVID-19 containment measures. Our results inform the public about opponents' motives, concerns and needs and open another perspective on the effects of the COVID-19 pandemic and its related containment measures.

Treatments and interventions for compulsive sexual behavior disorder with a focus on problematic pornography use: A preregistered systematic review.

Background and aims: Compulsive sexual behavior disorder (CSBD) which includes problematic pornography use (PPU) is a clinically relevant syndrome that has been included in the ICD-11 as impulse control disorder. The number of studies on treatments in CSBD and PPU increased in the last years. The current preregistered systematic review aimed for identifying treatment studies on CSBD and PPU as well as treatment effects on symptom severity and behavior enactment. Methods: The study was preregistered at Prospero International Prospective Register of Systematic Reviews (CRD42021252329). The literature search done in February 2022 at PubMed, Scopus, Web of Science, and PsycInfo, included original research published in peer-reviewed journals between 2000 to end 2021. The risk of bias was assessed with the CONSORT criteria. A quantitative synthesis based on effect sizes was done. Results: Overall 24 studies were identified. Four of these studies were randomized controlled trials. Treatment approaches included settings with cognitive behavior therapy components, psychotherapy methods, and psychopharmacological therapy. Receiving treatment seems to improve symptoms of CSBD and PPU. Especially, evidence for the efficacy of cognitive behavior therapy is present. Discussion and conclusions: There is first evidence for the effectiveness of treatment approaches such as cognitive behavior therapy. However, strong conclusions on the specificity of treatments should be drawn with caution. More rigorous and systematic methodological approaches are needed for future studies. Results may be informative for future research and the development of specific treatment programs for CSBD and PPU.

Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Treatment of Depression with Botulinum Toxin.

Injection of botulinum toxin (BoNT) into the glabellar region of the face is a novel therapeutic approach in the treatment of depression. This treatment method has several advantages, including few side effects and a long-lasting, depot-like effect. Here we review the clinical and experimental evidence for the antidepressant effect of BoNT injections as well as the theoretical background and possible mechanisms of action. Moreover, we provide practical instructions for the safe and effective application of BoNT in the treatment of depression. Finally, we describe the current status of the clinical development of BoNT as an antidepressant and give an outlook on its potential future role in the management of mental disorders.

Six Months of Piano Training in Healthy Elderly Stabilizes White Matter Microstructure in the Fornix, Compared to an Active Control Group.

While aging is characterized by neurodegeneration, musical training is associated with experience-driven brain plasticity and protection against age-related cognitive decline. However, evidence for the positive effects of musical training mostly comes from cross-sectional studies while randomized controlled trials with larger sample sizes are rare. The current study compares the influence of six months of piano training with music listening/musical culture lessons in 121 musically naïve healthy elderly individuals with regard to white matter properties using fixel-based analysis. Analyses revealed a significant fiber density decline in the music listening/musical culture group (but not in the piano group), after six months, in the fornix, which is a white matter tract that naturally declines with age. In addition, these changes in fiber density positively correlated to episodic memory task performances and the amount of weekly piano training. These findings not only provide further evidence for the involvement of the fornix in episodic memory encoding but also more importantly show that learning to play the piano at an advanced age may stabilize white matter microstructure of the fornix.

Evidence of cortical thickness increases in bilateral auditory brain structures following piano learning in older adults.

Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life-long musical activity. Cross-sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music-driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music-related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory-related regions of interest before and after 6 months of musical instruction in 134 healthy, right-handed, normal-hearing, musically-naive older adults (64-76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions-left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus-we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.

Corrigendum: Sexual Interaction in Digital Contexts and Its Implications for Sexual Health: A Conceptual Analysis.

[This corrects the article DOI: 10.3389/fpsyg.2021.769732.].