Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task.Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100–125 ms) and within ventral visual cortex during the N1 (150–170 ms) visual evoked components. During a later window implicated in visual completion (240–285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS.The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

The 22q11.2 Deletion Syndrome (22q11.2 DS) is one of the highest genetic risk factors for the development of schizophrenia spectrum disorders. In schizophrenia, reduced amplitude of the frequency mismatch negativity (fMMN) has been proposed as a promising neurophysiological marker for progressive brain pathology. In this longitudinal study in 22q11.2 DS, we investigate the progression of fMMN between childhood and adolescence, a vulnerable period for brain maturation. We measured evoked potentials to auditory oddball stimuli in the same sample of 16 patients with 22q11.2 DS and 14 age-matched controls in childhood and adolescence. In addition, we cross-sectionally compared an increased sample of 51 participants with 22q11.2 DS and 50 controls divided into two groups (8–14 and 14–20 years). The reported results are obtained using the fMMN difference waveforms. In the longitudinal design, the 22q11.2 deletion carriers exhibit a significant reduction in amplitude and a change in topographic patterns of the mismatch negativity response from childhood to adolescence. The same effect, reduced mismatch amplitude in adolescence, while preserved during childhood, is observed in the cross-sectional study. These results point towards functional changes within the brain network responsible for the fMMN. In addition, the adolescents with 22q11.2 DS displayed a significant increase in amplitude over central electrodes during the auditory N1 component. No such differences, reduced mismatch response nor increased N1, were observed in the typically developing group. These findings suggest different developmental trajectories of early auditory sensory processing in 22q11.2 DS and functional changes that emerge during the critical period of increased risk for schizophrenia spectrum disorders.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

A large proportion of schizophrenia patients treated with second generation antipsychotics will develop Obsessive Compulsive Disorder (OCD). However, there are few studies about the impact of this comorbidity and who is at higher risk. In this study of clozapine-treated patients, we aimed to determine the impact on outcome of clozapine-induced OCD, as well as the clinical and sociodemographic risk factors related to OCD-onset in clozapine patients. We had strict and novel inclusion criteria to minimise mis-identification of cases. The Obsessive-Compulsive Inventory-Revised (OCI-R) was used to divide 231 clozapine-treated patients into extreme cases of OCD (OCI  ≥ 24 or checking subscale ≥6) versus non-OCD (OCI <15 and checking subscale <4). The Global Assessment of Functioning (GAF), short version of Warwick-Edinburgh Wellbeing scale and Clinical Global Impression for schizophrenia (CGI) scales were used to determine outcome. Socio-demographic information was used to identify the risk factors for OCD development. We found that schizophrenia patients with OCD symptoms had a significantly lower patient rated wellbeing scores ( p < 0.001) only (no difference in clinician rated wellbeing scores), higher CGI positive ( p < 0.01) and higher CGI depressive scores ( p < 0.05). The only risk factors that reached significance level were higher treatment dose ( p < 0.01) and younger paternal age at birth ( p < 0.05). There is scope for future studies based on e.g. imaging and genetic studies to further investigate causality, and in improving clinician screening for OCD.

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