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Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
There is evidence that psychiatric diseases are accompanied by structural alterations in the human brain, partly reversible by pharmacological treatments. Several studies including Tost et al. (Nat.Neurosci.2010;13(8):920-2) investigated the effect of psychotropic drugs on neuronal plasticity pointing towards rapid pharmacologically induced brain grey matter variations, apart from already presumed slow structural changes within weeks. Here, we investigated the short-term (days) structural effects of SSRIs.
To identify structural changes of grey and white matter following 10d of oral administration (citalopram/escitalopram vs. placebo) in 18 healthy subjects investigated by magnetic resonance imaging (MRI) using voxel-based morphometry (VBM).
Study design: Randomized, cross-over, placebo-controlled, double-blind study.
ANOVA (grey matter: F(2,48) = 18.85, p < 0.05; white matter: F(2,48) = 17.79, p < 0.05) did not reveal suprathreshold clusters in grey or white matter.
This VBM-study does not support previous short-time (days) MR findings of pharmacologically-induced structural alterations in the brain, considering the lack of significant changes in grey and white matter volumes following 10d of SSRI administration. This divergence may be caused by dissent pharmacological effects of SSRIs compared to other psychotropic drugs.
Alterations of the serotonin-1A receptor (5-HT1A) and the hypothalamic-pituitary-adrenal (HPA) axis have been reported in depression and anxiety disorders. We previously showed a strong negative correlation between cortisol plasma levels and 5-HT1A receptor binding potential (BP) in patients with social anxiety disorder but not in healthy controls using PET .
To investigate the relationship of cortisol and the 5-HT1A BP in postmenopausal women, a population that is at increased risk of suffering from depressive symptoms.
Subjects: 19 postmenopausal women, aged 55.26 ± 4.98, medication free, no current substance abuse or hormone replacement therapy.
Dynamic measurements (50 frames, 90 min) were performed using the radioligand [carbonyl-11C]WAY100635 and a GE-Advance scanner. PET data were normalized to a ligand-specific template . Regions-of-interest (ROI) were defined as given in . TACs within ROIs were averaged and the 5-HT1A receptor BP was quantified using Logan-plot and PMOD 3.1. Measurement of total cortisol plasma levels was done using electrochemoluminescence.
We found negative correlations between cortisol and 5-HT1A BP in the midbrain (Spearman's rs = −0.54, p = 0.02), the median raphe nucleus (rs = −0.47, p = 0.04) and the nucleus accumbens (rs = −0.505, p = 0.03).
In line with our previous findings , the observed negative association between cortisol plasma levels and 5-HT1A BP might reflect an increased vulnerability for mood disorders in postmenopausal women.
The subgenual part of the anterior cingulate cortex (sgACC) has been frequently reported to be structurally and cytoarchitectually changed in major depressive disorder (MDD) and is also a promising target in deep brain stimulation in treatment-resistant MDD. Furthermore, substantial evidence demonstrates a high density of serotonin-1A (5-HT1A) receptors in the sgACC, a key area involved in emotional processing.
Here, we investigated the relationship between the 5-HT1A receptor in the sgACC and changes in regional grey matter volume with voxel-based morphometry.
PET ([carbonyl-11C]WAY-100635) was used to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance images from 32 healthy subjects (mean 26.68 ± 5.1 years; 17 women). Regression analysis was performed in SPM8 (p < .001 uncorr.) using sgACC 5-HT1A BPND as regressor, controlling for sex, age and total grey matter volume (GMV).
5-HT1A BPND in the sgACC was positively associated with regional GMV in the medial temporal gyri (T=4.37) and nucleus accumbens bilaterally (T = 4.19). Furthermore, sgACC 5-HT1A binding was negatively correlated with GMV within the inferior temporal gyri (T = 5.22) and putamen bilaterally (T = 5.12).
Our findings demonstrate structural relationships between sgACC 5-HT1A receptor binding and grey matter volume in the ventral striatum as well as in temporal regions, which both exhibit close neuronal connections with the sgACC. Moreover, the GMV of the ventral striatum has been reported to be decreased in patients with MDD. Conclusively, our results underpin the role of serotonergic neuronal transmission in cytoarchitectural processes within regions involved in the modulation of mood.
Dysfunctional neuroplasticity contributes to the pathogenesis of Alzheimer's disease, schizophrenia and depression. However, the underlying molecular mechanisms are not fully understood. Previous studies report neuromodulatory properties of the serotonin-1A (5-HT1A) receptor, which is also altered in these disorders. This suggests 5-HT1A mediated neuroplasticity as potential pathogenic factor.
The aim of this study was to demonstrate 5-HT1A mediated neuroplasticity in vivo.
We used positron emission tomography to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance imaging in 35 healthy subjects (mean 26.6 ±6.8 years; 17 women). Voxel-wise regression analysis was performed with gray matter volume (GMV) as dependent and 5-HT1A BPND as independent variable. Additionally, regression analysis was calculated with whole brain GMV as dependent variable and 5-HT1A BPND of the dorsal raphe nucleus (DRN) as independent variable. Control variables were age, sex and total GMV, respectively.
5-HT1A receptor density predicted GMV of the hippocampus, medial temporal cortex, inferior temporal cortex, medial occipital cortex and the pericalcarine region in each hemisphere (p < 0.05 false discovery rate corrected, R2: 0.308–0.503). These associations were independent from local numbers of neurons. Furthermore, 5−HT1A receptor levels in the DRN predicted GMV of the anterior cingulate cortex (p = 0.001, R2=0.656, uncorrected).
These results demonstrate 5-HT1A receptor mediated morphogenetic mechanisms in healthy human subjects' brains, which occur not only locally but also at the macro-network level. Finally, morphogenetic signaling investigated with multimodal neuroimaging could contribute to better understanding and diagnostic identification of gray matter loss in neuropsychiatric disorders.
The observance of possible somatic and environmental causes is essential to improve safety and efficacy in the treatment of agitated states. Severe agitation is considered a medical emergency requiring immediate psychopharmacologic intervention.
To establish a clinically applicable consensus statement based on evidence- as well as eminence-based medicine with respect to schizophrenia and mania.
The recommendations given are based on information from psychopharmacologic treatment studies as well as logistic and practical factors intrinsic to clinical settings.
Atypical antipsychotics given orally together with Lorazepam are considered the first-line treatment of agitated states in psychotic patients. Adequate communication with the patient is considered essential for effective oral administration. A novel alternative, Loxapine 4.5 mg or 9.1 mg (approved by the EMA 2013), is administered via an inhaler and exerts its sedative effects within 10 minutes. Inhalation may carry the benefit of greater patient acceptance. In contrast, intramuscular administration of antipsychotics is typically perceived by patients to be more invasive and persuasion or coercion may be necessary in severely ill patients. On the other hand, Aripiprazole, Haloperidole, Olanzapine and Ziprasidone show clinical efficacy within 15-30 minutes in psychopharmacologic trials when administered intramuscularly (i.m.). When taking extrapyramidal symptoms, QTc-prolongation and potential for combination with benzodiazepines into account, Aripiprazole i.m. carries the highest recommendation grade. Lorazepam may be administered intravenously. Currently, no antipsychotics are approved for intravenous administration.
This project gives recommendations which consider risk-benefit ratios and patient compliance.
Although discussed controversially, coercive practices during involuntary admission are common in mental health services. The impact of physical restraints on patients has not been sufficiently studied.
To investigate the subjective perception of patients during and after physical restraint.
47 patients in a psychiatric intermediate care facility experiencing belt fixation were interviewed and filled out self-assessment forms at 4 visits.
The median duration of restraint was 99 hours. Median VAS scores indicated moderate levels of anxiety. With increasing time span from the fixation, memory regarding this event decreased and patients experienced a regain of self-control. Consistently, 50% perceived high levels of coercion at admission, PTSD could be supposed in 25% of the patients.
Despite a considerable restraint of freedom, distress related to belt-fixation seems acceptable in our sample. Patients’ disapproval concerning restraint measures seems to diminish with time, probably related to decreasing memory regarding the fixation practice.
Seasonal affective disorder (SAD) is a subtype of recurrent depressive or bipolar disorder that is characterized by regular onset and remission of affective episodes at the same time of the year. The aim of the present study was to provide epidemiological data and data on the socioeconomic impact of SAD in the general population of Austria.
We conducted a computer-assisted telephone interview in 910 randomly selected subjects (577 females and 333 males) using the Seasonal Health Questionnaire (SHQ), the Seasonal Pattern Assessment Questionnaire (SPAQ), and the Sheehan Disability Scale (SDS). Telephone numbers were randomly drawn from all Austrian telephone books and transformed using the random last digits method. The last birthday method was employed to choose the target person for the interviews.
Out of our subjects, 2.5% fulfilled criteria for the seasonal pattern specifier according to DSM-5 and 2.4% (95% CI = 1.4–3.5%) were diagnosed with SAD. When applying the ICD-10 criteria 1.9% (95% CI = 0.9–2.8%) fulfilled SAD diagnostic criteria. The prevalence of fall-winter depression according to the Kasper-Rosenthal criteria was determined to be 3.5%. The criteria was fulfilled by 15.1% for subsyndromal SAD (s-SAD). We did not find any statistically significant gender differences in prevalence rates. When using the DSM-5 as a gold standard for the diagnosis of SAD, diagnosis derived from the SPAQ yielded a sensitivity of 31.8% and a specificity of 97.2%. Subjects with SAD had significantly higher scores on the SDS and higher rates of sick leave and days with reduced productivity than healthy subjects.
Prevalence estimates for SAD with the SHQ are lower than with the SPAQ. Our data are indicative of the substantial burden of disease and the socioeconomic impact of SAD. This epidemiological data shows a lack of gender differences in SAD prevalence. The higher rates of females in clinical SAD samples might, at least in part, be explained by lower help seeking behaviour in males.