The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

As attention-deficit/hyperactivity disorder (ADHD) is a feasible target for individuals aiming to procure stimulant medication or accommodations, there is a high clinical need for accurate assessment of adult ADHD. Proven falsifiability of commonly used diagnostic instruments is therefore of concern. The present study aimed to develop a new, ADHD-specific infrequency index to aid the detection of non-credible self-report. Disorder-specific adaptations of four detection strategies were embedded into the Conners’ Adult ADHD Rating Scales (CAARS) and tested for infrequency among credible neurotypical controls (n = 1001) and credible adults with ADHD (n = 100). The new index’ ability to detect instructed simulators (n = 242) and non-credible adults with ADHD (n = 22) was subsequently examined using ROC analyses. Applying a conservative cut-off score, the new index identified 30% of participants instructed to simulate ADHD while retaining a specificity of 98%. Items assessing supposed symptoms of ADHD proved most useful in distinguishing genuine patients with ADHD from simulators, whereas inquiries into unusual symptom combinations produced a small effect. The CAARS Infrequency Index (CII) outperformed the new infrequency index in terms of sensitivity (46%), but not overall classification accuracy as determined in ROC analyses. Neither the new infrequency index nor the CII detected non-credible adults diagnosed with ADHD with adequate accuracy. In contrast, both infrequency indices showed high classification accuracy when used to detect symptom over-report. Findings support the new indices’ utility as an adjunct measure in uncovering feigned ADHD, while underscoring the need to differentiate general over-reporting from specific forms of feigning.

Patients with Autism Spectrum Disorder (ASD) need to be provided with behavioral, psychological, educational, or skill-building interventions as early as possible. Cognitive Behavior Therapy has proven useful to manage such problems. There is also growing evidence on the usefulness of Virtual Reality Therapy (VRT) in treating various functional deficits in ASD. This exploratory study is aimed at assessing the changes in cognitive functions in children with ASD, and the putative subtending neurophysiological mechanisms, following the provision of rehab training using an innovative VRT system. Twenty patients with ASD, aged 6-15years, were provided with 24 sessions of VRT by using the pediatric module of the BTS NIRVANA System. Neuropsychological and EEG evaluations were carried out before and at the end of the training. After VRT, all patients showed a significant improvement in their cognitive-behavioral problems concerning attention processes, visuospatial cognition, and anxiety. These findings were paralleled by an evident reshape of frontoparietal connectivity in the alpha and theta frequency range. Our study suggests that VRT could be a useful and promising tool to improve ASD neurorehabilitation outcomes. This improvement is likely to occur through changes in frontoparietal network connectivity following VRT.

The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson’s disease symptoms and viral infections. Considering amantadine’s affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington’s disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine’s therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia.

There is accumulating evidence for auditory dysfunctions in patients with Parkinson's disease (PD). Moreover, a possible relationship has been suggested between altered auditory intensity processing and the hypophonic speech characteristics in PD. Nonetheless, further insight into the neurophysiological correlates of auditory intensity processing in patients with PD is needed primarily. In the present study, high-density EEG recordings were used to investigate intensity dependence of auditory evoked potentials (IDAEPs) in 14 patients with PD and 14 age- and gender-matched healthy control participants (HCs). Patients with PD were evaluated in both the on- and off-medication states. HCs were also evaluated twice. Significantly increased IDAEP of the N1/P2 was demonstrated in patients with PD evaluated in the on-medication state compared to HCs. Distinctive results were found for the N1 and P2 component. Regarding the N1 component, no differences in latency or amplitude were shown between patients with PD and HCs regardless of the medication state. In contrast, increased P2 amplitude was demonstrated in patients with PD evaluated in the on-medication state compared to the off-medication state and HCs. In addition to a dopaminergic deficiency, deficits in serotonergic neurotransmission in PD were shown based on increased IDAEP. Due to specific alterations of the N1-P2 complex, the current results suggest deficiencies in early-attentive inhibitory processing of auditory input in PD. This interpretation is consistent with the involvement of the basal ganglia and the role of dopaminergic and serotonergic neurotransmission in auditory gating.

The double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease) study in Japanese levodopa-treated patients with Parkinson’s disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [− 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [− 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [− 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

Patients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus–pituitary–adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15–40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15–48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson’s correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00702-021-02371-7.

Attention-deficit/hyperactivity disorder (ADHD) is commonly accompanied by functional impairments within personal, professional, and social context as well as further psychological distress. The role of perceived stress has been examined in this regard, although little is known about the influence of stress coping strategies. We examined the dynamics between ADHD symptomatology, stress coping strategies, and life impairments in a sample of 230 clinical and non-clinical adult individuals. ADHD was associated with low probability of choosing adaptive but high probability of implementing maladaptive stress coping strategies as well as with increased life impairments. Adaptive stress coping showed little effects beyond the associations between ADHD and life impairments, whereas some maladaptive coping strategies increased current life impairments over and above the effects of ADHD and further psychological distress. The present findings emphasize the need of professional support in adults with ADHD and the necessity to include stress coping strategies in respective treatment approaches aimed at reducing life impairments.

Endocannabinoid system (ECS) has been identified ever since cannabinoid, an active substance of Cannabis, was known to interact with endogenous cannabinoid (endocannabinoid/eCB) receptors. It later turned out that eCB was more intricate than previously thought. It has a pervasive role and exerts a multitude of cellular signaling mechanisms, regulating various physiological neurotransmission pathways in the human brain, including the dopaminergic (DA) system. eCB roles toward DA system were robust, clearly delineated, and reproducible with respect to physiological as well as pathological neurochemical and neurobehavioral manifestations of DA system, particularly those involving the nigrostriatal and mesocorticolimbic pathways. The eCB–DA system regulates the basics in the Maslow’s pyramid of hierarchy of needs required for individual survival such as food and sexual activity for reproductive purpose to those of higher needs in the pyramid, including self-actualization behaviors leading to achievement and reward (e.g., academic- and/or work-related performance and achievements). It is, thus, interesting to specifically discuss the eCB–DA system, not only on the molecular level, but also its tremendous potential to be developed as a future therapeutic strategy for various neuropsychiatric problems, including obesity, drug addiction and withdrawal, pathological hypersexuality, or low motivation behaviors.