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.
Abstract
Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched ...psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from “strongly recommended” to “potentially useful”. Evidence-based “therapeutic reference ranges” and “dose related reference ranges” were elaborated after an extensive literature search and a structured internal review process. A “laboratory alert level” was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.
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.
Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In ...psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.
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.
The basal ganglia form a forebrain system that collects signals from a large part of the neocortex, redistributes these cortical inputs both with respect to one another and with respect to inputs ...from the limbic system, and then focuses the inputs of this redistributed, integrated signals into particular regions of the frontal lobes and brainstem involved in aspects of motor planning and motor memory. Movement disorders associated with basal ganglia dysfunction comprise a spectrum of abnormalities that range from the hypokinetic disorder (from which Parkinson's disease, PD, is the best-known-example) at one extreme to the hyperkinetic disorder (exemplified by Huntington's disease and hemiballism) at the other. In addition to disorders of movement, major mental disorders including schizophrenic-like states and attention deficit hyperactivity disorder (ADHD) have been linked to abnormalities in the basal ganglia and their allied nuclei. In this paper we discuss recent evidence indicating that a dopamine-induced dysbalance of basal ganglia neurocircuitries may be an important pathophysiological component in PD, schizophrenia and ADHD. According to our model, the deprivation of dopaminergic nigro-striatal input, as in PD, reduces the positive feedback via the direct system, and increases the negative feedback via the indirect system. The critical consequences are an overactivity of the basal ganglia output sites with the resulting inhibition of thalamo-cortical drive. In schizophrenia the serious cognitive deficits might be partly a result of a hyperactivity of the inhibitory dopamine D(2) transmission system. Through this dysinhibition, the thalamus exhibits hyperactivity that overstimulates the cortex resulting in dysfunctions of perception, attention, stimulus distinction, information processing and affective regulation (inducing hallucinations and delusions) and motor disabilities. Recent studies have strongly suggested that a disturbance of the dopaminergic system is also involved in the pathophysiology of ADHD. The most convincing evidence comes from the demonstration of the efficacy of psychostimulants such as the dopamine transporter (DAT) blocker methylphenidate in the symptomatic treatment of ADHD. Genetic studies have shown an association between ADHD and genes involved in dopaminergic neurotransmission (for example the dopamine receptor genes DRD4 and DRD5, and the DAT gene DAT1). DAT knockout mice display a phenotype with increased locomotor activity, which is normalized by psychostimulant treatment. Finally, imaging studies demonstrated an increased density of DAT in the striatum of ADHD patients. Which system is disturbed and whether this system is hyper- or hypoactive is not unambiguously known yet.
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.
Hyperechogenicity of the substantia nigra (SN) is a sensitive marker for Parkinson’s disease (PD). Previously, a relation between SN echogenicity and iron as well as neuromelanin content could be ...described in 60 human brains. In the present study on a subset of 33 brains, SN echogenicity was found to be correlated with microglia activation (
ρ
= 0.46,
p
= 0.008) after correction for iron and neuromelanin content. These findings strengthen the hypothesis of a close pathophysiological connection between SN hyperechogenicity and PD pathology.
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.
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.
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