Person:

Finn, Christine

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA) (measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.

Background: Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603]) in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196), schizoaffective disorder (n = 62), bipolar disorder (n = 82), major depression (n = 30), and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24). Results: SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035) with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599), which was significantly underrepresented in this group (p = 0.0033) and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. Conclusion: Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.

A long-standing challenge for scientific and clinical work on suicidal behavior is that people often are motivated to deny or conceal suicidal thoughts. We proposed that people considering suicide would possess an objectively measurable attentional bias toward suicide-related stimuli, and that this bias would predict future suicidal behavior. Participants were 124 adults presenting to a psychiatric emergency department who were administered a modified emotional Stroop task and followed for six months. Suicide attempters showed an attentional bias toward suicide-related words relative to neutral words, and this bias was strongest among those who had made a more recent attempt. Importantly, this suicide-specific attentional bias predicted which people made a suicide attempt over the next six months, above and beyond other clinical predictors. Attentional bias toward more general negatively-valenced words did not predict any suicide-related outcomes, supporting the specificity of the observed effect. These results suggest that suicide-specific attentional bias can serve as a behavioral marker for suicidal risk, and ultimately improve scientific and clinical work on suicide-related outcomes.