Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi-target screening of oral fluid.

BACKGROUND AND OBJECTIVES: Numbers of drug-related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved. Opioid maintenance treatment (OMT) is a well-established therapy option among people with opioid dependence. The aim of this study was to assess concomitant substance abuse in opioid-dependent patients under OMT in two centers in Munich, Germany. METHODS: Oral fluid samples of opioid-dependent patients (n = 388) in OMT were randomly collected and analyzed by a multi-drug screening covering a wide range of psychotropic agents with UPLC-MS/MS techniques. RESULTS: Fifty-one percent of the patients had concomitant substance abuse of at least one non-prescribed substance, 32% were positive for substances that were not tested in routine urine diagnostics, especially pregabalin. Fifty-seven percent received take-home opioid medication, and 26% had contact with underage children. Among the take-home subgroup, a concomitant substance abuse of 43.5% was detected. Furthermore 52.5% of the patients with contact to underaged children exhibited concomitant substance abuse. CONCLUSIONS: Concomitant substance abuse is a serious issue among OMT patients. Screening for a broader range of substances than usually analyzed, reveals additional relevant abuse among OMT patients, including pregabalin-an anticonvulsant. SCIENTIFIC SIGNIFICANCE: Our study underscores the importance of monitoring a broad range of substances including others than usually screened in opioid-dependent patients in OMT. (Am J Addict 2018;XX:1-6).

The Relationship between Tourette's Syndrome and Infections.

Increasing evidence shows that infections and an activated immune status might be involved in the pathogene-sis of tic disorders. Studies discuss the influence of neurotrophic bacteria and viruses on different psychiatric disorders. In addition, signs of inflammation and immunological abnormalities have been described especially in schizophrenia and Tourette's syndrome (tic disorder). Neuroimaging studies revealed increased microglial activation in psychiatric diseases; indicating an inflammatory state of the CNS.However, it still remains unclear what the underlying mechanism is of how infectious agents could contribute to tic symp-toms. One hypothesis is that not only one particular infectious agent causes directly to the disease; instead different (chronic) infections influence the immune balance and are therefore involved in the pathology. In tic disorders, infections with group A streptococci, Borrelia burgdorferi or Mycoplasma pneumoniae seem to be associated with symptoms of the disease. Studies have shown that immunologic treatment improves and prevents the re-occurrence of clinical symptoms in Tourette's syndrome. Also post-infectious events by cross-reactive antibodies(against M-protein) and an altered dopamine rgic(noradrenergic) neurotransmission as well as inflammatory/immunological dysregulations were considered as possible mechanisms to cause symptoms. Another contributing factor to the pathogenesis of these diseases could be an activation of the tryptophan catabolism through infectious agents. Tryptophan functions as a precursor for neurotransmitters like se-rotonin and becomes degraded to products that can modulate the neurotransmitter balance.A deeper insight into the precise mechanism of how infectious agents influence immune parameter, tryptophan metabo-lism and the resulting neurotransmitter availability could help finding new therapeutic strategies.

Altered monocyte activation markers in Tourette's syndrome: a case-control study.

BACKGROUND: Infections and immunological processes are likely to be involved in the pathogenesis of Tourette's syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. METHODS: In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14 (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by immunoassays. RESULTS: We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. CONCLUSIONS: The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients.

BACKGROUND: Immune activation induces a pro-inflammatory state, which enhances the tryptophan degradation into kynurenine (KYN). The involvement of kynurenines has been shown in patients with major depression. Here, the effects of anti-inflammatory medication and antidepressants on cytokines and tryptophan metabolite changes in blood culture with immune challenge [bacterial mimetic lipopolysaccharide (LPS)] were investigated. MATERIALS AND METHODS: A total of 21 depressed patients and 38 matched controls were recruited. Whole blood cultures were stimulated with LPS and drugs were added (celecoxib, venlafaxine, reboxetine, imipramine and fluoxetine). Cytokines and kynurenines were analysed. RESULTS: After stimulation with LPS, the interferon-γ and interleukin (IL)-10 secretions were significantly higher in controls than in patients (p = 0.045, p = 0.032), respectively. Adding imipramine and celecoxib abolished the significance for IL-10. Challenge with LPS induced the kynurenine pathway in each group. Regarding the ratio KYNA/KYN, which indicated how much of KYN formed is further catabolised into the neuroprotective arm, the controls' blood cultures showed a significantly higher ratio (p = 0.045). DISCUSSION: Stimulation with LPS induced increased production of pro-inflammatory and anti-inflammatory cytokines in both groups, but higher responses in controls. This lower production of cytokine responses in depressed patients indicates that their immune cells are in a refractory phase, induced by a pre-existing pro-inflammatory state. For kynurenines, the whole metabolism was enhanced by LPS; however, an imbalance to neuroprotective metabolites was observed just in control blood. A drug effect could only be shown for imipramine and celecoxib, which were beneficial in terms of re-balancing the immune function but not in re-balancing neuroactive metabolites.

Intracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6.

Several studies have shown an involvement of the immune system, in particular the monocytic system, in the pathophysiology of schizophrenia. Beside others, the monocyte-derived cytokines TNF-α, IL-6 and IL-10 were found to be affected. Since cytokines are secreted by several different cell types, the cellular source is only clear if intracellular levels are measured. Thus, in order to study the monocytic system in schizophrenia, the intracellular levels of TNF-α, IL-6 and IL-10 were determined. The intracellular concentration of TNF-α, IL-6 and IL-10 in CD33 positive monocytes was evaluated in schizophrenic patients and controls with monoclonal antibodies against these cytokines. In addition, in vitro stimulation with lipopolysaccharide (LPS) or poly I/C, which mimic a bacterial and viral infection, was performed before immunocytochemistry. At baseline, monocytic IL-6 levels were significantly lower in schizophrenic patients than in controls. After stimulation with LPS, compared with baseline, monocytic intracellular IL-6 production tended to increase more in schizophrenic patients. The present results provide further support for the hypothesis of an involvement of a dysfunction of the monocytic system in the pathophysiology of schizophrenia and indicate that especially the pro-inflammatory immune response seems to be impaired.

Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease.

Neuroinflammation has been implicated in the pathology of Alzheimer's disease (AD) for decades. Still it has not been fully understood when and how inflammation arises in the course of AD. Whether inflammation is an underling cause or a resulting condition in AD remains unresolved. Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. However, also beneficial aspects of microglial activation have been identified. The purpose of this review is to highlight new insights into the detrimental and beneficial role of neuroinflammation in AD. It is our intention to focus on newer controversies in the field of microglia activation. Precisely, we want to shed light on whether neuroinflammation is associated to brain tissue damage and functional impairment or is there also a damage limiting activity. In regard to this, we discuss the limitations and the advantages of anti-inflammatory treatment options and identify what future implications might result from this underling neuroinflammation for AD therapy.