Discriminating unipolar and bipolar depression by means of fMRI and pattern classification: a pilot study

Bipolar disorders rank among the most debilitating psychiatric diseases. Bipolar depression is often misdiagnosed as unipolar depression, leading to suboptimal therapy and poor outcomes. Discriminating unipolar and bipolar depression at earlier stages of illness could therefore help to facilitate efficient and specific treatment. In the present study, the neurobiological underpinnings of emotion processing were investigated in a sample of unipolar and bipolar depressed patients matched for age, gender, and depression severity by means of fMRI. A pattern-classification approach was employed to discriminate the two samples. The pattern classification yielded up to 90 % accuracy rates discriminating the two groups. According to the feature weights of the multivariate maps, medial prefrontal and orbitofrontal regions contributed to classifications specific to unipolar depression, whereas stronger feature weights in dorsolateral prefrontal areas contribute to classifications as bipolar. Strong feature weights were observed in the amygdala for the negative faces condition, which were specific to unipolar depression, whereas higher amygdala features weights during the positive faces condition were observed, specific to bipolar subjects. Standard univariate fMRI analysis supports an interpretation, where this might be related to a higher responsiveness, by yielding a significant emotion × group interaction within the bilateral amygdala. We conclude that pattern-classification techniques could be a promising tool to classify acutely depressed subjects as unipolar or bipolar. However, since the present approach deals with small sample sizes, it should be considered as a proof-of-concept study. Hence, results have to be confirmed in larger samples preferably of unmedicated subjects.     

Dopaminergic projections from the VTA substantially contribute to the mesohabenular pathway in the rat

Recent evidence suggests that the lateral habenular complex (LHb) is a source of negative reward signals in midbrain dopaminergic neurons. LHb activity, in turn, is modulated by locally released dopamine, which is largely derived from the ventral tegmental area (VTA) via the mesohabenular pathway. Unfortunately, the presumed importance of this modulation has not been appreciated so far, as its intensity had been largely underestimated in previous reports. Consequently, the present study used contemporary techniques to reexamine the origin of dopaminergic fibers to the LHb. For this purpose, the retrograde tract-tracer gold-coupled wheatgerm agglutinin was injected into the LHb of fourteen rats. Four of these animals providing the most representative information were selected for detailed analysis. In total, 343 retrogradely labeled neurons were detected in the VTAs of these animals. By far most of them were found in the anterior VTA, accumulating in its ventral paramedian fields. About 47% (162) of retrogradely labeled cells displayed tyrosine hydroxylase immunoreactivity, suggesting that almost half of the mesohabenular neurons are dopaminergic. In addition, our data suggest that also incerto-hypothalamic and periventricular neurons contribute dopaminergic terminals to the LHb. The majority of LHb neurons, however, does not project to the origin of the mesohabenular pathway in the anterior VTA. Consequently, there might be no closed VTA-LHb-VTA loop. Instead, our data are in line with the idea that the anterior VTA via its projection to the medial part of the LHb may modulate the information flow from the limbic forebrain to monoaminergic midbrain nuclei.     

Corticotropin-releasing factor (CRF) receptor type 1-dependent modulation of synaptic plasticity

Mobile phones signals are pulse-modulated microwaves, and EEG studies suggest that the extremely low-frequency (ELF) pulse modulation has sleep effects. However, 'talk', 'listen' and 'standby' modes differ in the ELF (2, 8, and 217Hz) spectral components and specific absorption rates, but no sleep study has differentiated these modes. We used a GSM900 mobile phone controlled by a base-station simulator and a test SIM card to simulate these three specific modes, transmitted at 12.5% (23dBm) of maximum power. At weekly intervals, 10 healthy young adults, sleep restricted to 6h, were randomly and single-blind exposed to one of: talk, listen, standby and sham (nil signal) modes, for 30 min, at 13:30 h, whilst lying in a sound-proof, lit bedroom, with a thermally insulated silent phone beside the right ear. Bipolar EEGs were recorded continuously, and subjective ratings of sleepiness obtained every 3 min (before, during and after exposure). After exposure the phone and base-station were switched off, the bedroom darkened, and a 90 min sleep opportunity followed. We report on sleep onset using: (i) visually scored latency to onset of stage 2 sleep, (ii) EEG power spectral analysis. There was no condition effect for subjective sleepiness. Post-exposure, sleep latency after talk mode was markedly and significantly delayed beyond listen and sham modes. This condition effect over time was also quite evident in 1-4Hz EEG frontal power, which is a frequency range particularly sensitive to sleep onset. It is possible that 2, 8, 217Hz modulation may differentially affect sleep onset.     

Spatial reference- (not working- or procedural-) memory performance of aged rats in the water maze predicts the magnitude of sulpiride-induced facilitation of acetylcholine release by striatal slices

Cluster analysis of water-maze reference-memory performance distinguished subpopulations of young adult (3-5 months), aged (25-27 months) unimpaired (AU) and aged impaired (AI) rats. Working-memory performances of AU and AI rats were close to normal (though young and aged rats differed in exploration strategies). All aged rats showed impaired procedural-memory. Electrically evoked release of tritium was assessed in striatal slices (preloaded with [(3)H]choline) in the presence of oxotremorine, physostigmine, atropine+physostigmine, quinpirole, nomifensine or sulpiride. Aged rats exhibited reduced accumulation of [(3)H]choline (-30%) and weaker transmitter release. Drug effects (highest concentration) were reductions of release by 44% (oxotremorine), 72% (physostigmine), 84% (quinpirole) and 65% (nomifensine) regardless of age. Sulpiride and atropine+physostigmine facilitated the release more efficiently in young rats versus aged rats. The sulpiride-induced facilitation was weaker in AI rats versus AU rats; it significantly correlated with reference-memory performance. The results confirm age-related alterations of cholinergic and dopaminergic striatal functions, and point to the possibility that alterations in the D(2)-mediated dopaminergic regulation of these functions contribute to age-related reference-memory deficits.     

The association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life in breast cancer survivors following standard adjuvant versus high-dose chemotherapy

OBJECTIVE: The possible association between neuropsychological impairment, self-perceived cognitive deficits, fatigue and health related quality of life has been studied in high-risk breast cancer survivors 5 years following standard adjuvant (n=23) versus high-dose chemotherapy (n=24) and in early-stage breast cancer patients (n=29) (comparison group) following radiation therapy. METHODS: A neuropsychological assessment covering attention, memory and executive functions was used together with the questionnaire for self-perceived deficits in attention (FEDA), the multidimensional fatigue inventory (MFI-20) and the EORTC-QLQ-C30. RESULTS: Findings have shown that neuropsychological impairment is not directly associated with self-perceived cognitive deficits, fatigue and HRQOL. However, 46% of patients reported self-perceived cognitive deficits and 82% of the patients complained about cancer related fatigue. Except for reduced activity we did not find significant group differences, even though patients who received standard-dose chemotherapy had consistently higher levels of self-perceived cognitive deficits and fatigue, and the lowest HRQOL. CONCLUSION: Results emphasize the need for psychosocial counseling and support during treatment phase and follow up care as well. Sensitive cancer-specific measures for the assessment of self-perceived cognitive deficits in different cognitive domains according to neuropsychological measurements are required. PRACTICE IMPLICATIONS: The role of self-perceived cognitive deficits and fatigue should be considered in educational interventions and counseling. Specific rehabilitation measures should be developed, implemented and evaluated in order to meet the needs of these patients and to decrease the frequency of cognitive deficits following cancer treatment.     

Medizinstudierendenauswahl in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Das Bundesverfassungsgericht überprüft aktuell, ob das Vergabeverfahren der Medizinstudienplätze mit dem...