Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.

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The present study employs a new framework to categorise the heterogeneous findings on the relationship between impaired reward processing and negative and affective symptoms of schizophrenia. Based on previous behavioural and neuroimaging studies we postulate that "wanting" (i.e. anticipation) of a reward is specifically related to apathy, whereas "liking" (i.e. hedonic impact) is related to anhedonia and depression-symptoms commonly observed in schizophrenia. Fifteen patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic drugs and fifteen healthy controls performed a probabilistic monetary incentive delay task while undergoing functional magnetic resonance imaging. At the group level we found no significant differences between patients and controls in neural activation during anticipation or receipt of a reward. However, in patients with schizophrenia specific relationships between ventral-striatal activation and symptoms were observed. Ventral-striatal activation during reward anticipation was negatively correlated with apathy, while activation during receipt of reward was negatively correlated with severity of depressive symptoms. These results suggest that the link between negative symptoms and reward anticipation might specifically relate to apathy, i.e. a lack of motivation and drive. Impaired hedonic reward processing might contribute to the development of depressive symptoms in patients with schizophrenia, but it is not directly associated with self-rated anhedonia. These results indicate the necessity of more specifically differentiating negative and affective symptoms in schizophrenia in order to understand the role of the reward system in their pathogenesis.

Impaired behavioral response shifting in anorexia nervosa seems to be associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop that is involved in motivation-related behavior. In contrast, anorexia nervosa patients showed predominant activation of frontoparietal networks that is indicative of effortful and supervisory cognitive control during task performance.

The electroencephalographic response to transcranial magnetic stimulation (TMS) recently has been established as a direct parameter of motor cortex excitability. Its N100 component was suggested to reflect an inhibitory response. We investigated influences of cerebral maturation on TMS-evoked N100 in 6- to 10-year-old healthy children. We used a forewarned reaction time (contingent negative variation) task to test the effects of response preparation and sensory attention on N100 amplitude. Single-pulse TMS of motor cortex at 105% motor threshold intensity evoked N100 amplitudes of more than 100 microV in resting children (visible in single trials), which correlated negatively with age and positively with absolute stimulation intensity. During late contingent negative variation, which involves preactivation of the cortical structures necessary for a fast response, N100 amplitude was significantly reduced. We conclude that (1) N100 amplitude reduction during late contingent negative variation provides further evidence that TMS-evoked N100 reflects inhibitory processes, (2) response preparation and attention modulate N100, and (3) TMS-evoked N100 undergoes maturational changes and could serve to test cortical integrity and inhibitory function in children. Parallels between the inhibitory N100 after TMS (provoking massive synchronous excitation) and the inhibitory wave component of epileptic spike wave complexes are suggested.

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