Gisela Irmisch

Background: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3) could play a role in addictive behavior. Interactions between BDNF and dopamine transmission influence the alcohol intake. It has been hypothesized that extensive alcohol consumption leads to diminished circulating BDNF levels and impaired BDNF-mediated protective mechanisms. What is more, alcohol dependency causes changes in lipid metabolism which in turn may influence the neurotrophin system. Methods: In this study, we tested the hypothesis that alcohol withdrawal increases the serum levels of BDNF in alcoholic patients and investigated correlations between serum BDNF and NT3 and alcohol in breath as well as with the body-mass-index (BMI), lipoprotein profiles and lifestyle factors in 110 male in-patients diagnosed with alcohol addiction on the first day after admission and at discharge. Results: The intoxication level (alcohol in breath at admission) was significantly correlated with liver enzymes and BDNF concentrations (R = .28; p = .004). Patients with positive breath-alcohol test at admission had about 9 times higher NT3 levels and higher liver enzyme concentration levels than nonintoxicated subjects. Alcohol intoxicated patients with pathological aspartate aminase (ASAT) levels had even higher NT3 level (F = 5.41; p = .022). The concentration of NT3 was positively associated with the (BMI) (admission R = .36; p = .004; discharge R = .33; p = .001), and the obese patients had 3 to 5 times higher NT3 concentration than the others. Low-density lipoprotein (LDL) concentration levels were found to positively correlate with NT3 concentration levels (admission R = .025; p = .015 discharge R = .24; p = .23). Conclusion: Other than expected, the levels of NT3 and to a lesser extent BDNF levels, were found to be significantly increased in acute alcohol abuse. Alcohol deprivation did not significantly change the serum neurotrophin levels at admission. NT3 levels were positively correlated with the BMI and LDL levels. Because of expected difference between genders, we recommend investigating these correlations further in patients of both genders.

Alcohol-induced damages such as brain atrophy and fatty liver are closely related to a disturbed lipid metabolism. In animal models, a linkage between chronic alcohol consumption and changes in fatty acid (FA) composition in various organs and cells is well known and there is some indication that this phenomenon could be linked to behavioural alterations associated with alcohol addiction such as craving. However, the influence of ethanol on secretory FA has not been investigated so far. In this study, we therefore aimed at investigating whether there is a significant change of serum FA composition in patients suffering from alcohol dependence. We compared patients before and after treatment (detoxication) with control individuals who did not suffer from addiction. The roles of age, the duration and intensity of alcohol use and lifestyles were considered. Serum FA was measured in 73 male ethanol dependent patients before and after alcohol withdrawal in an in-patient setting. Additionally, of this group, 45 patients were matched with 45 healthy male volunteers as controls. We found significant differences in the FA composition before and after detoxication as well as between patients and controls. After detoxication, the values changed towards the ones in healthy controls. The main finding during acute alcohol use was an increased oleic acid concentration above the level of the linoleic acid concentration. An elevated oleic/linoleic acid ratio seems to be a state marker for acute alcohol use and may be a relevant trait marker during detoxification and possibly the subsequent therapeutic measures. The results of this pilot study need to be replicated in a larger study also including female patients. Further, the specificity of this potential biomarker needs to be determined.

Objective. Polyunsaturated fatty acids (PUFAs) have shown to be helpful in the therapy of ADHD. Various stabilizing co-factors may contribute to this effect, as like magnesium (Mg). Mg supports fatty acid enzyme activity and is essential for the neuronal activity. However, the way of Mg to influence psychic processes, particularly in ADHS, is not yet known precisely. Therefore, in this study the concentrations of further lipid parameters were assessed. We intended to prove, if there is a lack of Mg and someone different lipoprotein concentration in ADHD patients compared to controls. Methods. In nine boys with ADHD (8.2 ± 0.6 years) and 11 controls (7.9 ± 0.87 years), blood serum Mg, total cholesterol, triglycerides, Lipoprotein Lipase, total Phospholipids, Apolipoproteins a and b, HDL- and LDL-cholesterol were measured, under two different stressful conditions. Results. In ADHD, Mg and HDL concentrations were significantly higher and Apob lower than in controls. Conclusions. Contrary to our supposition, in ADHD was no lack, but an excess of Mg. HDL was hightened and Apob lowered. Lipoprotein metabolism seems to be modified in ADHD.

Polyunsaturated Fatty acids (PUFAs) seem to be helpful in the therapy of depression. Zinc (Zn) may be one co-factor contributing to their antidepressive effect. Zn acts lipid protective and is a constituent of fatty acid metabolism enzymes. In animals, an antidepressive effect of Zn was already demonstrated. Therefore, if and how Zn and PUFAs correlate in depressive patients or in individuals from the general population was investigated. Blood samples were collected from 88 depressive in-patients and 88 volunteers from the general population matched for age-group and gender (each 32 men and 56 women, 21–70 years) for measurement of Zn (colorimetric) and of 12 fatty acids (FAs) (by capillary gas-chromatography). Severity of depression in patients was assessed by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). Zn concentration was independent of age, gender and body-mass-index and significantly correlated with the severity of depression measured by BDI (r = 0.26; P = 0.034) in depressive patients,. HDRS was inversely correlated with gammalinolenic acid concentration (r = −0.24; P = 0.029). Median serum Zn concentration in depressive patients did not differ from control individuals. Zn was correlated with myristic acid concentration (r = 0.22; P < 0.05) in controls from the general population; and a negative correlation between Zn and dihomogammalinolenic acid concentration (r = −0.26; P < 0.05) was found in depressive inpatients. FA composition in serum significantly differed between depressive and healthy persons: Depressive patients had higher stearic and arachidonic acid (AA) concentration. Relative to AA, their eicosapentaenoic and docosapentaenoic acid concentration were diminished compared to the general populations group. These results do not confirm the hypothesis of a general lack of Zn in depressive disorders, but Zn concentrations differed dependent on comorbid disorders and severity of depression. In depressive patients and control persons Zn concentration is associated with different FAs indicating diverging metabolic pathways.

Bei Patienten mit depressiven Störungen werden Dysbalancen von Omega-3– und Omega-6-Fettsäuren (FS) diskutiert. Studienergebnisse wiesen einen antidepressiven Effekt einer repetitiven transkraniellen Magnetstimulation (rTMS) nach. Ziel unserer Studie war, die FS-Konzentrationen im Verlauf einer rTMS bei depressiven Patienten und Zusammenhänge zwischen Schweregrad der Depressivität und FS-Mustern zu ermitteln. Hierzu wurden 30 Patienten mit einer Depression in eine doppelblinde Plazebo-kontrollierte Studie eingeschlossen, erhielten entweder eine hochfrequente rTMS über dem linken, eine niedrigfrequente rTMS über dem rechten dorsolateralen präfrontalen Kortex oder eine Scheinbehandlung über einen Zeitraum von 10 Tagen. Vor und nach der Behandlungsserie wurden der Schweregrad der Depressivität, die psychomotorische Beeinträchtigung sowie die Serum-Konzentrationen der mehrfach ungesättigten FS analysiert. Während sich der Schweregrad der Depressivität in allen Gruppen besserte, war die psychomotorische Beeinträchtigung nur nach den realen rTMS-Formen rückläufig. Nach der hochfrequenten rTMS zeigte sich zusätzlich ein signifikanter Anstieg des FSQuotienten, während dies nach den anderen rTMS-Formen nicht der Fall war. Die Wertigkeit der FS-Konzentrationen als Marker für den Behandlungserfolg im Rahmen einer Depression wird diskutiert. In depression a dysbalance of Omega-3– and Omega-6-fatty acids (FA) is discussed. Results of studies with repetitive transcranial magnetic stimulation (rTMS) showed an antidepressive efficacy. The aim of our study was to measure the FA-concentrations in depressive patients during a repetitive transcranial magnetic stimulation. Correlations between severity of depression and fatty acid concentrations were analyzed. 30 patients with depression were included in a double-blind, placebo-controlled study using two different real stimulation procedures. The patients received either an high frequency rTMS over left, a low frequency rTMS over right dorsolateral prefrontal cortex or a sham stimulation over 10 days. Severity of depression, psychomotor retardation and concentrations of FA were analyzed at baseline and after the rTMS treatment phase. Severity of depression was reduced in all groups. Regarding psychomotor retardation a significant reduction was evident after real rTMS. After high frequency rTMS a significant increase of the quotient of FA in comparison to the other kind of rTMS occurred. The valence of FA-concentrations as a marker for response to antidepressive treatment will be discussed.