According to the monoamine hypothesis, the development of depression is associated with dysfunctions of the serotonergic system. Alterations in the serotonin transporter gene (5-HTTLPR), the ...serotonergic activity in the brain, and the content of serotonin (5-HT) have been related to depression and were examined separately by previous studies. This study investigates these parameters in 89 depressed patients and 89 healthy participants. We investigated the serotonergic activity measured by the loudness dependence of auditory evoked potentials (LDAEP). In addition to the examination of the serotonin content (serum and platelet), enzyme-linked immunosorbent assays (ELISA) were used and 5-HTTLPR genotypes were analyzed. We observed a lower serotonin content in patients compared to healthy participants. Further, we noticed a correlation between anxiety and depression-associated symptoms with serotonergic activity. Patients treated with SSRI/SNRI showed decreased contents of serum serotonin compared to patients without any psychotropic medication or other psychotropic medications. Since the serotonergic activity, peripheral serotonin content, and 5-HTTLPR were unrelated, the results suggest independent alterations of central and peripheral serotonergic systems in depression. In line with this finding, serotonergic activity was related to anxiety and depression symptoms. Furthermore, the applied medication seems to influence serum serotonin content in patients with depression.
Background and Aims
People with mental illness have worse physical health and reduced life expectancy compared to the general population. Nevertheless, their medical care is often insufficient. The ...present study aimed to investigate the somatic status of people with mental illness with a focus on somatic diagnoses, metabolic risk factors, regular somatic care, and routine check‐ups.
Methods
This study used a 14‐item questionnaire to survey the somatic care situation of psychiatric university hospital patients. Main survey topics were psychiatric and somatic diagnoses, metabolic risk factors, regular somatic care, and routine check‐ups.
Results
Four‐hundred and thirty‐five people with mental illness (48.3% male, mean age 45.4 years) were included. More than three quarters of the participating people with mental illness had access to a general practitioner. People with affective and anxiety disorders reported significantly more contact with medical specialists for somatic diseases, but schizophrenic patients did not receive enough care. Not all people with mental illness and on psychiatric medication received regular somatic care. Somatic diseases increased with number of diagnoses, and the duration of the psychiatric illness was positively correlated with treatment motivation.
Conclusion
The observed unmet medical needs in this study might reflect the lack of treatment motivation in people with mental illness, but could also represent their obstacles to access care as well as a suboptimal communication between the treating psychiatrist and the referring general practitioner. Increasing awareness of somatic diseases in psychiatric patients and easier access to somatic care have to be implemented in psychiatric clinical routine. The risk of stigmatization in somatic institutions and the lack of self‐care management in people with mental illness are complicating factors.
Background
The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives ...attention.
Method
In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5‐HT2A rs6311, and 5‐HT1A rs6295 by high‐resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self‐questionnaires. Fifty‐nine patients participated in a second appointment to measure the concentration of AEA, 2‐AG, and symptoms of depression and anxiety.
Results
We observed higher AEA and decreased 2‐AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2‐AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2‐AG. Gender differences were found concerning increased 2‐AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5‐HT1A rs6295 and 5‐HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients.
Conclusion
In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2‐AG and AEA, and genetic variations of the 5‐HT1A and 5‐HT2A could play a role in patients with depression and may be involved in a depressive disorder.
The present study showed an altered endocannabinoid system and the genetic variations of the 5‐HT1A, 5‐HT2A, and CNR1 genes in patients with a depressive disorder compared to healthy participants.
The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids ...anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.
Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.
Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.
Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.
Attention deficit hyperactivity disorder (ADHD) is a common pediatric psychiatric disorder, frequently treated with methylphenidate (MPH). Recently, MPH's cardiovascular safety has been questioned by ...observational studies describing an increased cardiovascular risk in adults and blood pressure alterations in children. We considered members of the L-arginine (Arg)/nitric oxide (NO) pathway as possible early cardiovascular risk factors in pediatric ADHD children. They include the NO metabolites, nitrite and nitrate, the NO precursor Arg, and asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor and a cardiovascular risk factor in adults. We conducted a prospective clinical trial with 42 ADHD children (aged 6-16 years) with (
= 19) and without (
= 23) MPH treatment. Age-matched children without ADHD (
= 43) served as controls. All plasma and urine metabolites were determined by gas chromatography-mass spectrometry. We observed higher plasma nitrite and lower plasma ADMA concentrations in the ADHD children. MPH-treated ADHD children had higher plasma nitrite concentrations than MPH-untreated ADHD children. As NOS activity is basally inhibited by ADMA, MPH treatment seems to have decreased the inhibitory potency of ADMA. Percentiles of systolic blood pressure were higher in MPH-treated ADHD children. The underlying mechanisms and their implications in the MPH therapy of pediatric ADHD with MPH remain to be elucidated in larger cohorts.
Alterations in peripheral serotonin concentrations and an imbalanced immune system have been reported in patients with depression. Cytokines and T regulatory (Treg) cells may play an important role ...in the development of depression. This study investigates the levels of cytokines and Treg cells, as well as the concentration of serotonin (5‐HT) in the blood of 89 patients suffering from depression and 89 healthy participants between two acquisitions. We investigated the state of health before (T1) and after (T2) psychological and pharmacological therapy. Both cytokine (IL‐6, IL‐10, TNF‐α, and INF‐γ) and 5‐HT levels in the blood were measured by enzyme‐linked immunosorbent assays. The levels of CD4+CD25+ Treg cells were determined by flow cytometric analysis. Patients with depression showed significantly higher serum levels of IL‐6 and INF‐γ, no altered serum levels of IL‐10 and TNF‐α, and decreased platelet and serum 5‐HT levels compared with healthy participants at the first acquisition. In addition, the symptoms of depression and anxiety, the TNF‐α level, and the amount of CD4+CD25+ cells in the blood were decreased from the first to the second acquisition. Further, a correlation between IL‐6 and platelet 5‐HT has been observed in patients. An imbalance of the immune system in patients with depression and an association of the serotonergic system and cytokines were observed. These results indicate that the development of depression might be related to several interacting proteins, including cytokines and 5‐HT, and the treatment affects imbalances of these factors.
Patients with depression showed decreased 5‐HT contents in the peripheral blood, elevated levels of proinflammatory cytokines, and grand symptoms of depression and anxiety compared to healthy participants. During the treatment the symptoms of depression and anxiety, also the values of TNF‐α/ CD4+CD25+ cells were reduced, and the content of serum serotonin was improved. The study indicates an imbalance of the immune system and a dysregulation in the serotonergic system in patients with depression.
Attention deficit hyperactivity disorder (ADHD) is a mental disorder that was once thought to occur only in children. Meanwhile, it is known that adults can also be affected. The first-line drug in ...children and adults to treat symptoms of inattention, impulsivity, lack of self-regulation, and hyperactivity is methylphenidate (MPH). Known adverse effects of MPH include cardiovascular problems, such as elevated blood pressure and heart rate. Therefore, biomarkers to monitor potential cardiovascular side effects of MPH are needed. The l-Arginine/Nitric oxide (Arg/NO) pathway is involved in noradrenaline and dopamine release as well as in normal cardiovascular functioning and is therefore a prime candidate for the search of biomarkers. The aim of the present study was to investigate the Arg/NO pathway as well as oxidative stress in adult ADHD patients in plasma and urine and the potential influence of MPH medication.
In plasma and urine samples of 29 adults with ADHD (39.2 ± 10.9 years) and 32 healthy adults serving as controls (CO) (38.0 ± 11.6 years) the major NO metabolites nitrite and nitrate, Arg, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) as well as malondialdehyde (MDA) were measured by gas chromatography–mass spectrometry.
Of the 29 patients with ADHD 14 were currently without MPH treatment (-MPH) and 15 were treated with MPH (+MPH). Plasma nitrate concentrations were significantly higher in patients not treated with MPH vs. CO (-MPH 60.3 μM 46.2–76.0 vs. CO 44.4 μM 35.0–52.7; p = 0.002), while plasma nitrite tended to be higher in -MPH patients (2.77 μM 2.26–3.27) vs. CO (2.13 μM 1.50–2.93; p = 0.053). Additionally, plasma creatinine concentrations were significantly different, with -MPH showing significantly higher concentrations than the other two groups (-MPH 141 μM 128–159; +MPH 96.2 μM 70.2–140; Co 75.9 μM 62.0–94.7; p < 0.001). Urinary creatinine excretion tended to be lowest in -MPH group vs. +MPH and CO (-MPH 11.4 ± 8.88 mM; +MPH 20.7 ± 9.82 mM; 16.6 ± 7.82 mM; p = 0.076). None of the other metabolites, including MDA, a marker of oxidative stress, showed a difference between the groups.
Adult patients with ADHD, who are not treated with MPH (-MPH), showed varied Arg/NO pathway, but Arg bioavailability seemed to be consistent over the groups. Our findings imply that urinary reabsorption may be increase and/or excretion of nitrite and nitrate may be decreased in ADHD, resulting in an increase in the plasma concentration of nitrite. MPH seems to partially reverse these effects by not yet known mechanisms, and does not affect oxidative stress.
•The l-arginine/nitric oxide pathway is altered in adult ADHD patients.•The bioavailability of l-arginine appears to be unchanged in ADHD patients.•ADHD patients show elevated plasma nitrite concentrations.•Methylphenidate seems to partially reverse plasma nitrite elevation.
Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle ...illness trajectories, and investigate genetic associations.
To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement.
This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 and analyzed from November 2016 to January 2018, and prospective validation data were extracted in October 2018 and analyzed from January to May 2019.
A clinical battery of 188 variables measuring demographic characteristics, clinical history, symptoms, functioning, and cognition was decomposed using nonnegative matrix factorization clustering. Subtype-specific illness courses were compared with mixed models and polygenic scores with analysis of covariance. Supervised learning was used to replicate results in validation data with the most reliably discriminative 45 variables.
Of the 765 individuals in the discovery sample, 341 (44.6%) were women, and the mean (SD) age was 42.7 (12.9) years. Five subgroups were found and labeled as affective psychosis (n = 252), suicidal psychosis (n = 44), depressive psychosis (n = 131), high-functioning psychosis (n = 252), and severe psychosis (n = 86). Illness courses with significant quadratic interaction terms were found for psychosis symptoms (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean SD partial η2 = 0.014 0.003) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort.
Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.
The newly developed app TellUs is a digital offering for psychiatric outpatient treatment that includes diagnostic and therapeutic tools. The aim of this study was to test the clinical efficiency and ...patient satisfaction of TellUs.
Sixty-four patients with depressive disorder took part in the study for 3 months. The intervention group was treated digitally with TellUs and the control group received visiting treatment (treatment as usual) during that time.
In both groups, a significant decrease of depressive symptoms and general strain through psychological symptoms, along with an increase of quality of life in the psychological domain, was shown. Furthermore, both groups were highly satisfied with the treatment.
TellUs was shown to be equivalent to treatment as usual in terms of clinical efficiency and patient satisfaction.
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