Cerebral white matter changes (WMC) represent cerebrovascular disease (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies/Parkinson's Disease Dementia (DLB/PDD). Predictors of treatment response are controversial.

To investigate the effect of WMC severity on response to ChEIs in dementia.

CT or MRI brain scans were rated for WMC severity in 243 patients taking ChEIs for dementia. Raters were blind to patients' clinical risk factors, dementia subtype and course of illness. Effects of WMC severity on rates of decline in cognition, function and behaviour were analysed for 140 patients treated for nine months or longer. Analysis was performed for this group as a whole and within diagnostic subgroups AD and DLB/PDD. The main outcome measure was rate of change in Mini Mental State Examination (MMSE) score. Secondary measures were rates of change in scores on the Cambridge Cognitive Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton Assessment Procedures for the Elderly – Behaviour Rating Scale (CAPE-BRS).

There was no significant correlation between severity of WMC and any specified outcome variable for the cohort as a whole or for patients with AD. In patients with DLB/PDD, higher WMC scores were associated with more rapid cognitive decline.

Increased WMC severity does not predict response to ChEIs in AD, but may weaken response to ChEIs in patients with DLB/PDD.

Evidence for acetylcholinesterase inhibitors (ACIs) available consists mainly of trials conducted by pharmaceutical companies. There are substantial differences between participants in clinical trials and patients in normal clinical settings.

To evaluate the use of ACIs in a clinical setting.

Hospital records of 454 patients prescribed ACIs over a 6-year period were analysed. In our catchment area of 50,000 people over the age of 65 approximately 100 new patients per year received treatment with ACIs.

The rate of decline on ACIs was less than half of that expected in an untreated population. A significant difference was found between patients with a baseline MMSE scores greater than 20 and those with a score between 10 and 20.

Our participants were older than in clinical trials and those with significant medical problems and relative contraindications were not excluded. ACIs are as useful in AD as they are in DLB/PDD and there were no differences between donepezil and rivastigmine. A baseline MMSE score of 20-10 might predict better response to treatment.

Primary care physicians are in the key position for early recognition and management of memory disorders. The study investigates their competence for this task longitudinally.

Written case vignettes on slight memory disorders (case 1) and moderate dementia (case 2) were presented to primary care physicians in their practices in 1993 and 2001. A standardised open interview was performed and the psychosocial focus remained secret.

Both studies were representative with response rates of 82.1% (n=145) and 71.8% (n=122). From 1993 to 2001 the rate of dementia diagnoses increased and those of vascular encephalopathy/organic brain disease decreased significantly. However, overall rates for diagnosis of Alzheimer dementia remained at about 25% for primary and 50% for differential diagnostic considerations. Vascular diagnoses kept dominating. The diagnostic tools showed a significant increase of the use of neuropsychological screening tests and of thyroid screen in moderate dementia. Neuroimaging would be applied significantly by significantly less physicians (<20%). Antidementia drug prescriptions decreased dramatically mainly regarding the conventional nootropics. Cholinesterase Inhibitors would be prescribed by less than 10% of the physicians. However, knowledge on psychosocial help increased significantly.

Competence changes over time can be investigated with this method. Primary care physicians' competence remains too low without systematic training. Especially Alzheimer's dementia will not be early recognized and adequate treated.

To date, psychostimulants constitute the most efficacious drugs in the treatment of ADHD with variable response rates ranging from 25% to 76%. Although remarkably safe, stimulant treatment is associated with potential shortcomings. Furthermore, adults with ADHD often suffer from concurrent disorders (anxiety, depression, tics and drug dependence)and stimulants are potentially abusable. Therefore a variety of alternative non-stimulants medications have been explored.

All available controlled trials of non-stimulants in adults ADHD patients were retrieved from Pubmed, PsycInfo and Mbase.

Only 17 controlled trials have been published. The compounds used are: desipramine, atomoxetine, modafinil, nicotine, ABT 418, guanfacine, selegiline, bupropion, lithium and pycnogenol. Effects seen in incontrolled studies are in general better than in well designed RCT's. Apart from trials with atomoxetine and bupropion the sample sizes are small. Most studies exclude patients with comorbid disorders, so that the study sample differs considerably from that in clinical practice. Most studies do not include assessment from significant others and some report improvement on a variety of neuropsychological measurements of executive functioning which cannot been translated into better daily functioning.

Sofar the non-stimulants are still hampered by their inferior effectsize compared to stimulants, the need for daily dosing to maintain their clinical efficacy and a delay in the onset of their clinical effects.

Deficits in response inhibition are considered as candidate endophenotypes of altered prefrontal brain function in Attention Deficit Hyperactivity Disorder (ADHD). Electrophysiological methods like Event-Related Potentials (ERPs) are adequate to measure abnormalities in brain functions underlying those deficits and to assess functionally relevant polymorphisms directly affecting neurotransmission systems and brain function. This principle of imaging genomics with ERPs has been demonstrated as early as 1999 for the serotonin transporter promoter polymorphism affecting prefrontal brain function (Fallgatter et al., International Journal of Neuropsychopharmacology, 1999).

We employed a multi-channel EEG during performance of a Go-NoGo task to assess the electrophysiological basis of response inhibition. The ERP-measure derived from this protocol was termed NoGo-Anteriorisation (NGA) and is characterized by a high interindividual stability, high short- and long-term test-retest reliability and, moreover, is independent from age- and gender.

In patients with ADHD during childhood and adulthood the NGA was diminished as compared to age- and sexmatched healthy controls. Furthermore, a three-dimensional source location analysis with LORETA indicated an electrical dysfunction of the ACC in the patient groups. Moreover, the 158 val/val variants of the COMT gene were associated with an even worse prefrontal brain function.

These results exemplify the measurement of disease related disturbances in brain function in ADHD with ERPs. Future studies will show whether such electrophysiological endophenotypes may contribute to the diagnosis of subgroups of ADHD and whether they may serve as endophenotypes to further clarify genetic contributions to the disease.

Executive and mnemonic impairments have been well documented in the high-risk states for development of psychosis and have been pinpointed as a possible core neuropsychological dysfunction. However, their neurofunctional correlates are still not clear.

fMRI was used in 17 patients at risk for developing psychosis (ARMS, “at risk mental state”), 10 patients with a first episode of psychosis (FEP) and 15 age-matched healthy comparison subjects to examine neural responses to increasing difficulty of mnemonic engagement in an object–location paired associate memory task. Groups were matched in terms of age, IQ, gender, and psychopathology ratings. Accuracy and reaction time were recorded during the scan.

As the mnemonic load increased, response latency increased and response accuracy decreased in an approximately linear fashion. No main effect for group was observed. However, a trend towards decreased accuracy in FEP subjects, as compared with controls, was evident. As the task difficulty increased, increased brain activity was observed in the medial frontal cortex and in the medial posterior parietal cortex. Between-groups differences in activation were observed in a cluster spanning the MFG, SFG and SMA and in the right precuneus. However, these neurofunctional abnormalities were more evident in the most demanding level of the task than in the easy level, with the ARMS groups showing less activation than controls and higher activation than FEP.

Abnormal neural activity in medial frontal cortex and posterior parietal cortex during paired associate learning task may represent a neurofunctional substrates of vulnerability to psychosis.

The present study evaluated the association between the WHO (Ten) Well-being index and major depression assessed by the Major Depression Inventory (MDI) and Schedules for Clinical Assessment in Neuropsychiatry (SCAN). The main aim was to examine how well the WHO (Ten) Well-being index worked as a screening instrument for depression in a population-based sample.

A questionnaire including the WHO (Ten) Well-being index and the MDI was sent out to a randomly selected adult Swedish population and 10 441 persons participated. Psychiatrists using SCAN interviewed a selected sample. Sensitivity, specificity, Receiver Operating Characteristics (ROC) and Area Under the Curve (AUC) were calculated.

When a cut-off score ≤ 8 for the Well-being scale was used and depression according to SCAN was the index of validity the sensitivity was 0.81 and the specificity 0.81. When depression according to the algorithm of the MDI was used the sensitivity was 0.89 and the specificity was 0.86 at a cut-off score of ≤ 12. There were no age or gender differences between true positive persons versus false negative persons. The AUC was good (0.86) when using SCAN and when using the DSM-IV algorithm of the MDI excellent (0.93).

The WHO (Ten) Well-being scale can be used as s simple screening instrument for depression in population-based studies. However, the scale needs to be further evaluated in order to examine if the recommended cut-off score in the present study could be replicated in other surveys.

Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (≤1Hz) repetitive transcranial magnetic stimulation (rTMS) diminishes auditory hallucinations. A neuroimaging study elucidating the effect of rTMS in auditory hallucinations has not yet been published.

To evaluate the changes of brain metabolism after low-frequency rTMS in patients with auditory hallucinations.

Low-frequency rTMS (0.9Hz, 100% of motor threshold, 20 min.) applied to the left temporo-parietal cortex was used for ten days in the treatment of medication-resistant auditory hallucinations in schizophrenia (N=12). The effect of rTMS on the brain metabolism (18FDG PET) was measured before and after the treatment.

We found a significant improvement in the total and positive symptoms, and on the hallucination scales (HCS, AHRS). The rTMS decreased the brain metabolism in the left superior temporal gyrus and in interconnected regions and effected increases in the contralateral cortex and in the frontal lobes (SPM).

The findings implicate that the effect is connected with decreased metabolism in the cortex underlying the rTMS site while facilitation of metabolism is propagated by transcallosal and intrahemispheric connections. Stereotactic neuronavigation of rTMS (SN rTMS) is a unique technology to target the rTMS coil with a high degree of anatomic accuracy based on the evaluation of the neuroimaging. Our finding enable the use of stereotactic neuronavigation of rTMS in auditory hallucination and pilot data are presented.

This research was supported by the projects 1M0517 MSMT CR and NR8792 of IGA MZ CR.

AISD (Antipsychotic induced sexual dysfunction) is one of the most important reasons for therapeutic noncompliance. AISD is often described as adverse events of hyperprolactinemia, induced due to immoderate D2 occupancy (more than 72%) in the tuberoinfundibular system. Consequently the sex steroids decrease. Regulation of Follitropin secretion involves a complex balance between stimulation by GnRH from the hypothalamus, inhibitory feedback by sex steroids, Inhibins A (in both sexes) and B (in male) from the gonads and autocrine/paracrine modulation by Activin and Follistatin within the pituitary.

We have tried to verify the hypothesis that inhibins could be a better marker of sexual dysfunction than prolactinemia in patients (16 men and 11 women) with stable therapy and psychopathology with a diagnosis of schizophrenia, age 18-40 years. Follitropin, Lutropin, Prolactin, TSH, Estradiol, Progesterone, Testosterone, Inhibin A (in women) and B, Activin and Follistatin were used to measure the endocrinological condition. Structured Adverse Effects Rating Scale, UKU (hyperprolactinemia), Arizona Sexual Experience Scale and International Index of Erectile dysfunction in men were used to detect sexual dysfunction.

Inhibin B in men, not in women, correlated with sexual dysfunction (p < 0.05). Prolactinemia did not correlate with this side effect, it correlated with the absence of the menstrual cycle in women.

Inhibin B may be used as a marker of the functional condition in antipsychotic induced sexual dysfunction in men. Results are limited by the sample size. Further study is needed to evaluate the importance and specificity of Inhibin B.

Mirror Neurons (MNs) constitute a system for matching action observation and execution and for recognising socially meaningful gesticulation. Here we explored the possibility that this system also contributes to emotional processing. To test this hypothesis, a novel affective startle paradigm was developed to investigate MNs and emotional processing.

Fifty healthy participants completed a startle experiment where they were presented with 36 emotionally valenced pictures equally split into positive, negative and neutral categories. All pictures were preceded by emotionally congruent primes, half of which consisted of a videoclip showing a biologically meaningful hand-object interaction and half that consisted of a control stimulus showing static images of the interaction. Acoustic startle probes were presented during picture viewing at 2.5, 3, 3.5, 4 and 4.5 second intervals and startle eyeblink responses were recorded.

Startle amplitude was magnified only for emotionally negative pictures. This effect was present when the images were preceded by a prime containing biological motion but not a static prime. This result was found for startle probes presented at 2.5s, but not at longer intervals.

The MN system is involved in emotional processing, as shown by modulation of the startle reflex when a negative picture is primed with emotionally congruent biological motion. Further, this modulation occurs only when the time interval between picture presentation and startle probe is relatively short, suggesting that the MN system may provide an early warning of threat-related actions.

Trail making test (TMT) was developed as a neuropsychological test evaluating frontal lobe function. However, the contribution of frontal lobe in results of TMT is still controversial because studies in patients with brain injuries suggest the role of basal ganglia rather than frontal lobe in results of TMT.

To examine the contribution of frontal lobe in the results of TMT, we measured blood flow in frontal cortex during performance of computer version TMT-A and TMT-B.

Sixteen healthy student volunteers (8 male, 25.9±5.3 year old; 8 female, 22.0±2.9 year old) was used in the study. Seven laser beam probes and 8 sensor probes were put on frontal lobe, and absorbance of 695 nm and 830 nm infrared beams were measured at 10Hz by optic topography (ETG 4000, Hitachi, Medical Corporation, Tokyo, Japan).

Concentration of deoxyhemoglobin was decreased while concentration of oxyhemoglobin was increased in the prefrontal cortex during the performance of TMT-A and TMT-B.

The results suggest that blood flow increases in the prefrontal cortex during the performance of TMT, and possible involvement of this brain region in the performance of TMT.

Malondialdehyde (MDA) is a common biologic marker of oxidative stress used in psychiatric research. Data regarding MDA levels in healthy subjects are controversial. One factor affecting MDA levels may stem from the existence of a circadian rhythm of MDA formation. The objective of this study consists of investigating whether MDA formation has a circadian rhythm of formation in healthy human subjects.

The sample was comprised by 9 healthy male subjects. None of them had a history of medical or neurological disease and routine laboratory parameters were normal. The study was carried out in accordance with the Helsinki Declaration and all subjects gave written informed consent before their inclusion. Blood samples were extracted at 12:00 and 2:00 in December 2004. The same routine was followed during the two experimental sessions. Serum MDA was determined by the thiobarbituric acid reactive substance (TBARS) according to the method of Ohkaba et al (1979).

The sample was comprised by 9 male healthy subjects (age 33.0±11.7). There were significant differences in MDA levels between 12:00 and 2:00 (2.33±1.01 vs. 1.58±0.48, p<0.015).

MDA has a circadian rhythm of formation with higher levels at 12:00 than 2:00. This variation in circadian MDA levels of formation should be accounted when researching in this field.