Chris Bervoets

Less cognitive and neurological deficits in schizophrenia patients carrying risk variant in ZNF804A.

Background: The rs1344706 single nucleotide polymorphism in the ZNF804A gene is a common variant with strong evidence for association with schizophrenia. Recent studies show an association of rs1344706 with cognitive functioning, and there is some evidence suggesting that the risk allele may increase susceptibility for a subtype of schizophrenia with relatively spared cognition. Methods: We tested the effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive domains (working memory, processing speed and attention) shown to be severely impaired in schizophrenia. Also we investigated the effect of rs1344706 on the severity of neurological soft signs, subtle impairments in motor and sensory functions highly frequent in schizophrenia patients. Neurological soft signs and cognitive deficits are central features of schizophrenia and are tightly linked with clinical, social and functional outcome. Results: Our results show an association of higher rs1344706 risk allele load with improved performance on processing speed and with fewer neurological soft signs. Conclusions: Together with other studies, our findings suggest that ZNF804A is associated with a subtype of schizophrenia with better cognitive and neurological functioning. Discovery of the specific pathways through which ZNF804A is exerting this effect may lead to better prevention, diagnosis and treatment for a specific group of schizophrenia patients.

The nature of the relationship of psychomotor slowing with negative symptomatology in schizophrenia.

Introduction Psychomotor slowing is an important feature of schizophrenia and the relation with negative symptoms is not fully understood. This study aims, first, to investigate the association between negative symptoms and psychomotor slowing. Second, we want to investigate whether fine motor slowing reflects clinically observable gross motor slowing. Methods In 53 stabilised adult patients with schizophrenia, negative symptoms were assessed using the Positive and Negative Syndrome Scale negative subscale (PANSS-N) with two calculated factors entering the analysis: an expressivity factor and a volitional factor. Psychomotor slowing was assessed by using a modified version of the Salpêtrière Retardation Rating Scale, the Finger Tapping Test, and a writing task measuring fine psychomotor slowing. Results Negative symptomatology is associated with difficulties in the initiation of fine motor movements, r=.334, p<.05, whilst planning and execution are not. The volitional factor, r=−.407, p=.005, but not the expressivity factor, r=.060, p=.689, is significantly associated with psychomotor slowing. No associations between fine and clinically observable gross psychomotor functioning were found. Conclusions These findings indicate that higher values of negative symptomatology—more specifically the volitional deficit cluster—affect motor initiation, indicating a heterogeneity in the PANSS-N factorial structure, and that gross and fine psychomotor functioning are affected independently.

Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders†

The GWAS‐based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage‐dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient‐control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7 kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17–26 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.

Longitudinal evaluation of the psychomotor syndrome in schizophrenia

Little is known about the longitudinal course of psychomotor signs and symptoms after illness onset in schizophrenia. Therefore, a 1-year follow-up study was conducted in which patients with schizophrenia were assessed three times with an extensive battery of psychomotor rating scales and tests. The syndromic structure of psychomotor symptoms was also studied. In accordance with a neurodevelopmental view on schizophrenia, psychomotor functioning was found to remain stable or improve slightly. Prospective studies with longer follow-up periods are needed to rule out the possibility of neurodegeneration in subgroups of patients and to evaluate possible covariation in the course of psychomotor symptoms.

Long-term electrical stimulation of bed nucleus of stria terminalis for obsessive-compulsive disorder.

We previously reported that bilateral electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) effectively reduces symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we used a linear mixed model to investigate the evolution of symptomatic and functional status of our patients (n=24) and examined if baseline variables could predict this evolution. Data were collected during routine, clinical psychiatric visits. Our analysis showed a long-term, sustained effect of electrical stimulation in the IC/BST. After a fast initial decline of OCD symptoms, these symptoms remain relatively stable. In addition, we found a strong ON/OFF effect of stimulation (e.g., due to battery depletion). Our data also show that it is not the surgical procedure but rather the electrical stimulation that drives the improvement in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. The Beck Depression Inventory (BDI) at baseline was the only predictor significantly related to the evolution of the Y-BOCS. A higher BDI at baseline seemed to be related to a smaller decrease of the Y-BOCS over time. In conclusion, electrical stimulation in the IC/BST has a fast and sustained effect on OCD and comorbid symptoms and functional status of patients.