Leonora Franke

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM

Summary.We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [123I]-ADAM SPECT. The midbrain SERT availability (SERT V3″) was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 ± 0.27 vs. 0.71 ± 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects

SummaryBackground. A robust association between “suicidality” and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. Methods. In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT2A receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. Results. Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls.Mean Vmax of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients.Mean KD for the platelet 5HT2A receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls.The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher Vmax of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. Conclusions. In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

Aromatic amino acids in weight-recovered females with anorexia nervosa.

OBJECTIVE Most previous studies investigating amino acid levels in anorexia nervosa (AN) have focused on acutely underweight patients. The present study assessed the availability of aromatic amino acids in the plasma of weight-recovered outpatients with AN (recAN) in comparison to acutely underweight AN patients (acAN) and healthy control woman (HCW). METHOD Plasma tryptophan (TRP), tyrosine (TYR), and phenylalanine (PHEN) as well as leptin concentration were determined in 32 recAN, 32 acAN, and 32 HCW. RESULTS Both recAN and acAN patients showed significantly lower levels of TRP and PHEN when compared to HCW. TYR was reduced in acAN patients only. DISCUSSION Normal weight and normal leptin levels but lower availability of TRP and PHEN in recAN patients might indicate that outside a tightly controlled setting these patients still engage in abnormal eating patterns. Reduced peripheral availability of these precursor amino acids could impact on 5-HT and catecholamine functioning in the brain.

Three Cases of Successful Tryptophan Add-On or Monotherapy of Hepatitis C and IFNα-Associated Mood Disorders

BACKGROUND Interferon-alpha (IFN(alpha))-associated mood disorder is a major complication of treatment for chronic hepatitis C. METHOD The authors report on three patients infected with chronic hepatitis C showing severe depressive symptoms during or after IFN(alpha) treatment. Because patients had lowered tryptophan blood levels and did not response to antidepressants, they received tryptophan up to a dosage of 1,000 mg/day as mono- or add-on treatment. RESULTS Tryptophan, used as augmentation or monotherapeutic treatment, led to a significant improvement of depressive symptoms in all three patients. CONCLUSION A tryptophan deficit seems to be involved in the pathophysiology of persistent mood changes during and after IFN(alpha) treatment.

S100B in underweight and weight-recovered patients with anorexia nervosa.

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.

A role for plasma aromatic amino acids in injurious pecking behavior in laying hens

Injurious pecking, including feather pecking (FP), is one of the most prevalent causes of mortality for commercial laying hens. The underlying biological mechanisms of FP are not yet fully understood, but they could be related to alterations in the serotonin (5-HT) and/or dopamine (DA) circuits within the brain. In the past, the central synthesis of 5-HT and DA was found to be influenced by the availability of their precursors, aromatic amino acids (AAA) such as tryptophan (TRP), phenylalanine (PHE), and tyrosine (TYR), in blood plasma, which are transported across the blood-brain-barrier into the brain. Because knowledge about plasma levels of AAA in laying hens is very limited, the present study compared the AAA profiles of a large sample of laying hens from two genetic lines: one selected for low mortality (LM) due to injurious pecking (n=129 birds) and one high production line (HP) selected for high egg-production only (n=132 birds). Head, comb, and feather covering were scored at the end of the experiment. Blood samples were collected at weeks 24 and 29 of age and were analysed for AAA using high performance liquid chromatography. Neither FP nor feather damage was observed in the present study, but aggressive pecking directed at the head/neck area occurred in several groups with an onset of this aberrant behavior between weeks 22 and 29. Eight HP pens and seven LM pens were affected by severe head/comb injuries inflicted via aggressive pecking. Therefore, our exploratory data analysis focused upon the possible interplay between the variability of our outcome measures (absolute levels of AAA in plasma as well as the ratios PHE/TYR and TRP/(PHE+TYR)) and the aggressive head/comb pecking as an expression of social stress within the pens. We found significantly lower TRP availability relative to PHE and TYR (TRP/(PHE+TYR) ratio) and higher TYR concentrations at week 24 in pens with an early onset of injurious aggressive behavior at weeks 22-23. This was most pronounced in the LM line, but at week 29, TRP availability normalized in both lines. It was furthermore evident that in LM birds, higher aggressive pecking activity per pen was associated with higher TYR levels (n=78 birds, r=0.643, p<0.001) and lower TRP/(PHE+TYR) ratios at week 24 (r=-0.541, p<0.001). In the HP birds, these associations were of lower strength and were negatively correlated (TYR: n=73, r=-0.308, p=0.005; TRP/(PHE/TYR) ratio: r=0.314, p=0.004). Our findings indicate that in LM birds, lower TRP availability at week 24 may be attributable to higher stress levels in pens where injurious aggressive pecking developed early on. These findings may lay the important groundwork for the analysis of AAA plasma levels as a useful avenue of research to investigate underlying physiological mechanisms of behavioral problems in laying hens.

A Preliminary Study on the Relationship between Platelet Serotonin Transporter Functionality, Depression, and Fatigue in Patients with Untreated Chronic Hepatitis C

Objective and Methods. Although the interaction between fatigue and depression in patients with chronic hepatitis C infection (HCV) has been recognized, the biological correlates of this observation have yet to be reported. We addressed this issue by examining serotonin transporter- (SERT-) driven [14C]-serotonin uptake rate (SUR) and serotonin content in platelets of 65 untreated HCV patients and 65 healthy control subjects (HCS). All patients completed report questionnaires for fatigue, depression, and general psychopathology. Structured interviews were conducted by a board-certified psychiatrist. Results. Whereas 36 of the patients experienced fatigue of moderate-to-severe intensity, only 16 reported symptoms of depression (BDI score > 10). Mean SUR in patients with depressive symptoms was significantly higher relative to the HCS, corresponding to a large Cohens effect size of d = 1.45 (95% CI = 0.66—1.83). Patients who rated their fatigue to have a marked impact on mood and activity displayed a moderate relationship between the BDI score and SUR (n = 18, r = 0.563, P = 0.015), which becomes stronger after controlling for age, gender, and thrombocytopenia (r part = 0.710, P = 0.003). In the univariate analysis, high fatigue interference score, thrombocytopenia, and high SUR were all significant predictors of depression. Conclusions. High SERT activity could be implicated in the expression of depressive symptoms especially in a subgroup of HCV patients who are feeling fatigue as markedly distressing.

Sustained Increase of 25-Hydroxyvitamin D Levels in Healthy Young Women during Wintertime after Three Suberythemal UV Irradiations-The MUVY Pilot Study.

Objectives Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study “MUVY” (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design. Methods 20 healthy young women (Fitzpatrick skin types I–III, aged 21–25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50. Results Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0–8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4–18.4) and 26.2 pmol/L (95%CI = 7.2–45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale “Vigor/Activity” and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8. Conclusions Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status. Trial Registration German Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274

P02-14 Gender differences in [123I]-ADAM binding to serotonin transporters in patients with major depression before and after treatment with Citalopram

Aims The aim was to determine the relation between characteristics of [123I]-ADAM binding to serotonin transporters (SERT) in several brain regions to different symptoms in patients diagnosed with major depressive disorder (MDD) and to analyze data for males and females separately. Differences of [123I]-ADAM binding in patients before and after treatment with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant Citalopram were assessed. Method 12 non medicated patients (5 females and 7 males) diagnosed with MDD were examined by SPECT with specific Serotonin transporter radioligand [123I]-ADAM before and after treatment with SSRI Citalopram. We administered the dose of 10 mg Citalopram per day intravenously at first day, followed by a 6 days period of oral application. After 7 days of treatment patients were examined for second time with SPECT. The relationships between [123I]-ADAM binding and different aspects of major depression represented by HAMD items, assessed twice by Hamilton Depression-Scale (HAMD) once at baseline and second after treatment period, were evaluated. Results We found significant correlations with significant gender differences between singular sub items of HAMD and indices of [123I]-ADAM binding in midbrain before and after treatment. These findings points to the need of data analysis separately in males and females. No correlations between HAMD total scores at baseline and indices were found. Conclusion SERT availability for 123-ADAM binding in the midbrain in drug naives as well as in treated patients with major depression disorder seems to be related to intensity of sub items in the HAMD and the outcome of treatment.

P03-246 Acute effect of blue light exposition on well-being and melatonin secretion in humans

Aim The aim of this study was to investigate the efficacy of blue light emitting diode units in suppression of melatonin secretion and to evaluate whether a single exposure can improve well being in healthy males and females (20/30) and in 15 women with premenstrual syndrome. Methods All study participants were of morning-type with a regular sleep schedule. On control day 1, the subjects were kept under dim illumination ( Results Overall, blue light improved significantly mental and physical complaints from pre-test to post-test (reduction in sum score of the Zerssens complaints scale by in average 30%) and reduced sleepiness, as measured by the VAS. There were gender-related differences, as well as differences related to the menstrual phase in females. Blue light reduced but not suppressed the gradual increase of melatonin in plasma with time mostly pronounced in the follicular phase. Conclusion A single exposition with blue light of low radiant flux density, as applied in our study, seems to be helpful in reducing mental and physical distress.