Explore the vast range of titles available.

About 60 years ago, the discovery of a deficiency of dopamine in the nigro-striatal system led to a variety of symptomatic therapeutic strategies to supplement dopamine and to substantially improve the quality of life of patients with Parkinson’s disease (PD). Since these seminal developments, neuropathological, neurochemical, molecular biological and genetic discoveries contributed to elucidate the pathology of PD. Oxidative stress, the consequences of reactive oxidative species, reduced antioxidative capacity including loss of glutathione, excitotoxicity, mitochondrial dysfunction, proteasomal dysfunction, apoptosis, lysosomal dysfunction, autophagy, suggested to be causal for ɑ-synuclein fibril formation and aggregation and contributing to neuroinflammation and neural cell death underlying this devastating disorder. However, there are no final conclusions about the triggered pathological mechanism(s) and the follow-up of pathological dysfunctions. Nevertheless, it is a fact, that iron, a major component of oxidative reactions, as well as neuromelanin, the major intraneuronal chelator of iron, undergo an age-dependent increase. And ageing is a major risk factor for PD. Iron is significantly increased in the substantia nigra pars compacta (SNpc) of PD. Reasons for this finding include disturbances in iron-related import and export mechanisms across the blood–brain barrier (BBB), localized opening of the BBB at the nigro-striatal tract including brain vessel pathology. Whether this pathology is of primary or secondary importance is not known. We assume that there is a better fit to the top-down hypotheses and pathogens entering the brain via the olfactory system, then to the bottom-up (gut-brain) hypothesis of PD pathology. Triggers for the bottom-up, the dual-hit and the top-down pathologies include chemicals, viruses and bacteria. If so, hepcidin, a regulator of iron absorption and its distribution into tissues, is suggested to play a major role in the pathogenesis of iron dyshomeostasis and risk for initiating and progressing ɑ-synuclein pathology. The role of glial components to the pathology of PD is still unknown. However, the dramatic loss of glutathione (GSH), which is mainly synthesized in glia, suggests dysfunction of this process, or GSH uptake into neurons. Loss of GSH and increase in SNpc iron concentration have been suggested to be early, may be even pre-symptomatic processes in the pathology of PD, despite the fact that they are progression factors. The role of glial ferritin isoforms has not been studied so far in detail in human post-mortem brain tissue and a close insight into their role in PD is called upon. In conclusion, “iron” is a major player in the pathology of PD. Selective chelation of excess iron at the site of the substantia nigra, where a dysfunction of the BBB is suggested, with peripherally acting iron chelators is suggested to contribute to the portfolio and therapeutic armamentarium of anti-Parkinson medications.

Asymmetry of dopaminergic neurodegeneration and subsequent lateralisation of motor symptoms are distinctive features of Parkinson’s disease compared to other forms of neurodegenerative or symptomatic parkinsonism. Even 200 years after the first description of the disease, the underlying causes for this striking clinicopathological feature are not yet fully understood. There is increasing evidence that lateralisation of disease is due to a complex interplay of hereditary and environmental factors that are reflected not only in the concept of dominant hemispheres and handedness but also in specific susceptibilities of neuronal subpopulations within the substantia nigra. As a consequence, not only the obvious lateralisation of motor symptoms occurs but also patterns of associated non-motor signs are defined, which include cognitive functions, sleep behaviour or olfaction. Better understanding of the mechanisms contributing to lateralisation of neurodegeneration and the resulting patterns of clinical phenotypes based on bilateral post-mortem brain analyses and clinical studies focusing on right/left hemispheric symptom origin will help to develop more targeted therapeutic approaches, taking into account subtypes of PD as a heterogeneous disorder.

Monoamine oxidase inhibitors (MAO-I) have been useful in the treatment of both psychiatric and neurological disorders over centuries. Here we focus on the development of this drug treatment. Focus is given on the use of irreversible MAO-Is as well as on reversible ones. Benefit and side effects are reported for Parkinsons disease, Alzheimers dementia, depression syndrome and panic disorders. The preclinical and clinical effects of selegiline with regard to neuroprotection are highlightened and the conclusion is drawn that there is good evidence for a clinical neuroprotective capacity based on the assumption that the 50 percent recovery of MAO-B is obtained already after a 10 days withdrawal of selegiline. There is also a focus on selegilines metabolism to amphetamine and metamphetamine. In order to avoid any such effects of metabolic compounds on the cardiovascular system Zydis Selegiline, a melt-tablet avoid of major metabolism to amphetamine and metamphetamine is described in detail. Developments in MAO-I research are discussed in detail as there are moclobemide, lacabemide, rasagiline. Interactions of MAO-I with tricyclics and serotonin selective reuptake inhibitors (SSRIs) are described as there is mentioning of interactions of MAO-Is with other compounds in general. Tables and figures report on clinical studies and on pharmacological properties of MAO-Is.

Energy management systems (EMS) play a crucial role in optimising thermal and electrical energy consumption in buildings and districts. DIMOSIM, a building and district simulation software, has been developed with a novel electric system model that allows for multi-level control strategies to simulate flexible consumption such as batteries. The new structure integrates simple and robust simulation algorithms while also enabling the external control strategies through socket coupling that can be on a zone, building or district level. This advancement allows researchers to test and implement state-of-the-art control techniques within a well-established simulation environment. This paper presents the development process of the model structure, detailing its design principles and technical implementation. To demonstrate its effectiveness, a case study was conducted using standard control algorithms. The results showed a significant improvement in energy performance, with more than 30% reduction in peak electricity consumption and an increase in self-consumption compared to a baseline without storages and controllers. This work enhances the capabilities of DIMOSIM, making it a powerful tool for researchers and engineers working on next-generation EMS solutions. The structure enables also coupling and interaction between electrical and thermal control signals, such as the use of heat pumps for flexibility issues.

The foundation of a German Society of Biological Psychiatry (DGBP) was initiated at the Second World Congress of Biological Psychiatry of the WFSBP in Barcelona in 1978. Its mission was and is to promote interdisciplinary research on the biology of mental disorders and to translate results of biological research into clinical practice. During the presidency of Peter Falkai, its tasks were defined to improve the quality and support of biologically oriented research in Germany by the DFG (Deutsche Forschungsgemeinschaft; German Research Foundation), BMBF (Bundesministerium für Bildung und Forschung) and EU (European Union), to promote young researchers doing biologically oriented research, to improve on the diagnosis and therapy of mental disorders and to advise policy makers by taking part in legal processes. The DGBP has been a corporate member of the WFSBP from its beginning, became a cooperative member of the DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde), later of the German Brain Council, and fostered relationships with other scientific societies. Over the past 45 years, more than twenty congresses were held in Germany and neighboring countries. Emerging from the pandemic, the DGBP is ready to continue its mission to promote interdisciplinary research on the biology of mental disorders with a focus on the development of young scientists and to translate results of biological research into clinical practice, with regard to pharmacotherapy in close cooperation with the Arbeitsgemeinschaft Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). In this sense, this article also aims to stimulate the cooperation of the society with other national and international partners and to foster new relationships with young scientists and professionals interested in the aims and goals of the DGBP.

Accumulated evidence suggests that the insulin-resistant brain state and cerebral glucose hypometabolism might be the cause, rather than the consequence, of the neurodegeneration found in a sporadic Alzheimer’s disease (sAD). We have explored whether the insulin receptor (IR) and the glucose transporter-2 (GLUT2), used here as their markers, are the early targets of intracerebroventricularly (icv) administered streptozotocin (STZ) in an STZ-icv rat model of sAD, and whether their changes are associated with the STZ-induced neuroinflammation. The expression of IR, GLUT2 and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence and western blot analysis in the parietal (PC) and the temporal (TC) cortex, in the hippocampus (HPC) and the hypothalamus. One hour after the STZ-icv administration (1.5 mg/kg), the GFAP immunoreactivity was significantly increased in all four regions, thus indicating the wide spread neuroinflammation, pronounced in the PC and the HPC. Changes in the GLUT2 (increment) and the IR (decrement) expression were mild in the areas close to the site of the STZ injection/release but pronounced in the ependymal lining cells of the third ventricle, thus indicating the possible metabolic implications. These results, together with the finding of the GLUT2-IR co-expression, and also the neuronal IR expression in PC, TC and HPC, indicate that the cerebral GLUT2 and IR should be further explored as the possible sAD etiopathogenic factors. It should be further clarified whether their alterations are the effect of a direct STZ-icv toxicity or they are triggered in a response to STZ-icv induced neuroinflammation.

The destruction of the dopaminergic neurons in the substantia nigra (SN) and consequent depletion of striatal dopamine elicits the main movement deficits related to Parkinson’s disease (PD). In the early stages of the illness, the motor symptoms are often exhibited asymmetrically. Thus, the onset of PD features starts on either the right or left side. The side of onset appears to determine the prognosis of the disorder and other features, such as right-side tremor dominance has a better prognosis in contrast to left-side dominant bradykinesia-rigidity. In addition, left-side onset of motor features is associated with cognitive decline. Therefore, an intricate relation appears to exist between the side of disease onset and progression/severity and other non-motor symptoms. Unilateral PD in turn corresponds to neuronal nigrostriatal degeneration in the contralateral hemisphere. Indeed positron emission tomography has demonstrated a positive correlation between symptom asymmetry and brain function (Hoorn et al. Parkinsonism Relat Disord 17:58–60, 2011 ), which corresponds to a unilateral pattern of degeneration. This phenomenon appears to be exclusive to PD. Additionally, the variation in motor symptom(s) dominance exhibited in the disorder conforms to the notion that PD is a spectrum disease with many sub-groups. Thus, clinical and post mortem studies on “lateralisation” may serve as a vital tool in understanding the mechanism(s) eliciting the characteristic destruction of the SN neurons. Additionally, it may be employed as a predictive indicator for the symptomology and prognosis of the illness thus allowing selective treatment strategies targeted at the pronounced hemispheric degeneration.

Therapeutic drug monitoring (TDM) data of antidepressant drugs are often evaluated using homogeneous samples of selected individuals without psychiatric or somatic comorbidity. These data may have limitations in transferability to everyday clinical practice. Hence, studies under naturalistic conditions are important to clarify the full clinical relevance of TDM of antidepressants. TDM analyses were retrospectively evaluated for a 3-year period from 2008 to 2010. The influence of gender and age on dose-corrected serum concentrations of antidepressants was examined in a standard clinical setting. 693 TDM analyses of amitriptyline and nortriptyline (AMI + NOR), 160 of citalopram (CIT), 152 of clomipramine and N -clomipramine (CLO +  N -CLO), 272 of doxepine and N -doxepine (DOX +  N -DOX), 359 of escitalopram (ESC), 198 of fluoxetine and N -fluoxetine (FLU +  N -FLU), 92 of maprotiline (MAP), 888 of mirtazapine (MIR), and 77 of sertraline (SER) remained in the sample. Females had significantly higher dose-corrected serum concentrations of AMI + NOR (32 %), CIT (29 %), DOX +  N -DOX (29 %), and MIR (20 %), and patients older than 60 years had significantly higher dose-corrected serum concentrations of AMI + NOR (21 %), CIT (40 %), DOX +  N -DOX (48 %), MAP (46 %), MIR (24 %), and SER (67 %). Comparing the two extreme groups, females >60 years showed a remarkably higher dose-corrected serum concentration of AMI + NOR (52 %), CIT (78 %), DOX +  N -DOX (86 %), and MIR (41 %) in contrast to males ≤60 years. Gender and age have a significant influence on the serum concentrations of different antidepressant drugs, and additive effects must be considered. TDM is recommended to reduce the risk of adverse effects due to supratherapeutic serum levels, also in a naturalistic clinical setting.

The role of neuroinflammation in the pathogenesis of neurodegenerative diseases has become more evident in recent years. Research on the etiology and pathogenesis of sporadic Alzheimer’s disease (AD) has focused on the role of chemokines such as CX3CL1, on the triggering receptors expressed by myeloid cells (TREMs), especially TREM2, and on the transcription factor/nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Here we analyzed the expression levels of CX3CL1, TREM2, and PPARγ in tissue homogenates from human brain regions that have different degrees of vulnerability to neuropathological AD-related changes to obtain insights into the pathogenesis and progression of AD. We found that CX3CL1 and TREM2, two genes related to neuroinflammation, are more highly expressed in brain regions with pronounced vulnerability to AD-related changes, such as the hippocampus, and that the expression levels reflect the course of the disease, whereas regions with low vulnerability to AD, seemed generally less affected by neuroinflammation. Furthermore, our results support previous findings of significantly higher CX3CL1 plasma levels in patients with mild to moderate AD than in patients with severe AD. Thus, CX3CL1 should be considered as promising additional marker for the early diagnosis of AD and underlines once more, the involvement of the neuroinflammation in the pathogenesis of this neurodegenerative disease.

Background Parkinson's disease (PD) is often accompanied by non-motor complications, such as dementia, depression, and psychotic symptoms, which worsen the prognosis and increase the personal and socioeconomic burden of disease. Prevalence estimates of these complications are quite variable and are lacking for the outpatient care sector. Methods As part of a larger, nationwide, cross-sectional epidemiological study in n = 315 neurological outpatient settings in Germany, this paper estimates the frequency of dementia and cognitive impairment in n = 873 outpatients meeting the UK Brain Bank criteria for idiopathic PD. Assessments were based on a clinical interview and neuropsychological assessments, including the Hoehn & Yahr rating and Unified Parkinson's Disease Rating Scale (UPDRS). Cognitive impairment was assessed by the Mini-Mental State Exam (MMSE), Clock Drawing Test (CDT) and the Parkinson Neuropsychometric Dementia Assessment (PANDA) and the clinician's diagnosis of dementia was based on the diagnostic criteria of DSMIV. Results Using standardized cutoff scores, the prevalence of cognitive impairment in the study sample as measured by various methods was 17.5% by MMSE (≤ 24), 41.8% by CDT (≥ 3), 43.6% by PANDA (≤ 14), and 28.6% met the DSM-IV criteria for dementia. All estimates increased with age and PD severity. Gender was an inconsistent contributor while illness duration had no significant impact on cognition. Multiple regression analyses revealed PD severity to be the strongest predictor of dementia risk (OR = 4.3; 95% CI: 2.1–9.1), while neuropsychiatric syndromes had independent, although modest additional contributions (OR = 2.5, 95% CI: 1.6–3.8). Conclusion Estimates of cognitive impairment and dementia in PD patients are largely dependent on the diagnostic measure used. Using established clinical diagnostic standards for dementia the overall rate on routine outpatient neurological care is 28.6%, but using more sensitive neuropsychological measures, rates for cognitive impairment might be up to 2-fold higher. The MMSE revealed strikingly low sensitivity. Neuropsychiatric syndromes, in addition to PD severity and age, have an independent – although modest – additional contribution to patients' risk for cognitive impairment and dementia.