Nitric oxide (NO) is a gaseous neurotransmitter thought to play important roles in several behavioral domains. On a neurobiological level, NO acts as the second messenger of the Nmethyl-D-aspartate receptor and interacts with both the dopaminergic as well as the serotonergic system. Thus, NO is a promising candidate molecule in the pathogenesis of endogenous psychoses and a potential target in their treatment. Furthermore, the chromosomal locus of the gene for the NO-producing enzyme NOS-I, 12q24.2, represents a major linkage hot spot for schizophrenic and bipolar disorder. To investigate whether the gene encoding NOS-I (NOS1) conveys to the genetic risk for those diseases, five NOS1 polymorphisms as well as a NOS1 mini-haplotype, consisting of two functional polymorphisms located in the transcriptional control region of NOS1, were examined in 195 chronic schizophrenic, 72 bipolar-I patients and 286 controls. Single-marker association analysis showed that the exon 1c promoter polymorphism was linked to schizophrenia (SCZ), whereas synonymous coding region polymorphisms were not associated with disease. Long promoter alleles of the repeat polymorphism were associated with less severe psychopathology. Analysis of the mini-haplotype also revealed a significant association with SCZ. Mutational screening did not detect novel exonic polymorphisms in patients, suggesting that regulatory rather than coding variants convey the genetic risk on psychosis. Finally, promoter polymorphisms impacted on prefrontal functioning as assessed by neuropsychological testing and electrophysiological parameters elicited by a Go-Nogo paradigm in 48 patients (continuous performance test). Collectively these findings suggest that regulatory polymorphisms of NOS1 contribute to the genetic risk for SCZ, and modulate prefrontal brain functioning.

An elevated cue-reactivity evoked by alcohol-related stimuli (cues) in alcohol-dependent patients has been described for different physiological variables, including electrophysiological measures, such as event-related potentials (ERPs). Cue-reactivity has, however, also been reported for social drinkers. The aim of this study is to assess the effect of the drinking behaviours of social drinkers on cue-reactivity as measured with ERPs. Forty alcohol-related and 40 neutral pictures were presented to 15 heavy and 15 light drinkers (all males). ERPs were recorded using 21 scalp electrodes. Stimuli were presented for 500 ms with an inter-stimulus interval of 2000 ms. Heavy social drinkers displayed a cue-reactivity of significantly higher amplitude at the frontal electrode location Fz, elicited by alcohol-related, as compared to neutral, pictures. This effect was not found in light social drinkers. The results indicate that the cue-reactivity previously found in alcohol-dependent patients is also present in social drinkers, and that electrophysiological cue-reactivity is associated with alcohol consumption.

Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), have been associated with ADHD. The rs4570625 G-allele polymorphisms of the TPH2 gene have already been related to altered reactivity of the brain during perception tasks with emotional stimuli in healthy adults. Here we investigated the influence of the ADHD related risk alleles for rs4570625 and for rs11178997 on prefrontal brain function during cognitive response control in large samples of adult ADHD patients (n = 124) and healthy controls (n = 84). Response control was elicited with a Go-NoGo task (continuous performance test; CPT) performed during recording of an ongoing EEG. From the resulting event-related potentials in the Go-and NoGo conditions of the CPT, the NoGo-anteriorization (NGA) has been calculated as a valid neurophysiological parameter for prefrontal brain function. In the current study, ADHD risk alleles of both polymorphisms were found to be associated with a reduction in the NGA in both healthy controls and ADHD patients. These findings are in line with the notion that genetic variations associated with altered serotonergic neurotransmission are also associated with the function of the prefrontal cortex during response inhibition. This mechanism might also be relevant in the pathophysiology of ADHD.

Quantitative electroencephalography (qEEG) and the Folstein Mini Mental State examination (MMSE) were obtained from 31 patients affected by probable dementia of Alzheimer’s type (DAT). qEEG data were examined both by spectral analysis (Fast Fourier Transformation) and by single frequency band topographical centroid, and compared with those of 24 healthy subjects of the same age group. DAT patients were found to have higher absolute power in the slow (delta and theta) frequency bands. Quantitative topographical assessment showed significantly more anteriorly located centers of gravity for the alpha and beta activity. Only alpha anteriorization was correlated with the degree of cognitive impairment as measured by the global deterioration scale and MMSE. It is concluded that quantitative topographical assessment was successful for the statistical handling of the EEG power maps, and to identify a potential parameter for the functional staging of the disease.

Our neuropsychological findings suggest that episodic autobiographical memory is affected in long-term patients with SPMS, possibly due to neurodegenerative processes in functional relevant brain regions.