SfN 2012—Functional Disturbances and Molecular Alterations in Psychosis
3 December 2012. The Society for Neuroscience Meeting was held on 13-17 October in New Orleans, Louisiana. On Sunday afternoon, October 14, a nanosymposium entitled Brain Alterations in Psychosis: Functional and Molecular was moderated by Sabina Berretta of Boston's Harvard Medical School.
Elena Ivleva of University of Texas Southwestern in Dallas described a study testing whether gray matter phenotypes in schizophrenia and bipolar disorder are similar across diagnoses, and thus whether psychosis is the organizing dimension. Using voxel-based morphometry, the researchers observed divergent gray matter phenotypes between schizophrenia/schizoaffective disorder and bipolar disorder with psychosis. However, the psychosis dimension included overlapping gray matter reductions in probands and relatives with schizophrenia spectrum personality disorders, but not unaffected relatives, suggesting that the dimensional conception of psychosis is a valuable research tool.
Felix Siebenhühner of the University of California, Santa Barbara, described a MEG study of a visual working memory task to examine the interaction between oscillatory frequency bands using a novel method to analyze statistical properties of functional brain networks within and across frequency bands. The work provides further evidence of oscillatory disturbances in schizophrenia, both in networks within frequency bands and those that span multiple frequencies.
Lisa Eyler of the University of California, San Diego, described medial prefrontal resting-state connectivity abnormalities in bipolar disorder. Although previous studies have reported default mode network abnormalities and altered medial prefrontal resting-state connectivity in the illness (Ongür et al., 2010) both used manic subjects. In the current study, Eyler and colleagues examined euthymic subjects, finding a general pattern of underconnectivity of medial prefrontal cortex with other cortical regions, suggesting that these alterations are disease state-independent.
Molly Simmonite of the United Kingdom’s University of Nottingham discussed the use of electroencephalography (EEG) to examine cross-frequency coupling in schizophrenia during an information processing task. Simmonite and colleagues observed decreased delta-theta and theta-gamma phase-amplitude coherence in the illness, providing further evidence that schizophrenia is characterized by a disruption of connectivity.
Joseph Shaffer of the University of North Carolina Chapel Hill described his work examining the relationship between severity of clinical symptoms, cognitive deficits, and resting-state functional connectivity in schizophrenia. These three measures were combined and an independent component analysis was performed in recent-onset schizophrenia subjects, familial high-risk subjects, and controls. Shaffer and colleagues found that schizophrenia symptom severity is associated with changes in connections between several cortical and subcortical regions—fronto-temporal and fronto-parietal connectivity in particular—and that connections in fronto-limbic and fronto-striatal networks are associated with cognitive performance.
Session moderator Sabina Berretta discussed the possible role that homeobox protein Otx2 may play in the maturation of parvalbumin interneurons and their surrounding perineuronal nets (PNNs), both of which are thought to be altered in schizophrenia (Pantazopoulos et al., 2010). Berretta presented data demonstrating that Otx2 is expressed in several cortical and subcortical brain regions and cell populations, and may play a role in both fetal brain development and postnatal brain maturation. Her lab is currently testing the hypothesis that Otx2 is altered in schizophrenia.
Following up on Berretta’s talk, her Harvard colleague Harry Pantazopoulos discussed the chondroitin sulfate proteoglycan aggregan, a critical component of perineuronal nets (PNNs). Using postmortem tissue, the researchers found reductions in the number and density of aggregan-positive PNNs in the amygdala of both schizophrenia and bipolar disorder, although the exact pattern of alterations differed between the two illnesses. Pantazopoulos concluded that these alterations suggest a critical disruption of neuronal functions such as neural oscillations that are subserved by interneurons.
Michelle Mighdoll of the Lieber Institute for Brain Development in Baltimore, Maryland reviewed previous work characterizing cation chloride co-transporter genes NKCC1 and KCC2 across development and in schizophrenia (see SRF related news story). Following up on previous findings demonstrating that the expression of alternative transcripts of NKCC1 was decreased in the prefrontal cortex of subjects with schizophrenia and significantly associated with NKCC1 polymorphisms, Mighdoll and colleagues examined the association between allelic variation in NKCC1 and fMRI signal. They found that one SNP was associated with poorer cognitive performance and less efficient engagement of DLPFC during a working memory task.
Next up was Ilaria Guella of the University of California, Irvine, who examined levels of a microRNA, miR-137, in the dorsolateral prefrontal cortex of schizophrenia, bipolar disorder, and control subjects. Guella and colleagues showed that miR-137 expression is significantly lower in control subjects homozygous for the risk allele of a SNP in miR-137, but not significant in the schizophrenia or bipolar disorder cohorts. Moreover, validated miR-137 target and schizophrenia risk gene TCF4 is expressed at higher levels in homozygous risk allele carriers in all three groups.
Keri Barksdale of the University of Alabama at Birmingham, examined the synaptic organization and mitochondrial morphology of the anterior cingulate cortex in schizophrenia using electron microscopy in postmortem tissue. The researchers observed a reduced synaptic density and proportion of synapses containing at least one mitochondrion in schizophrenia, as well as altered mitochondrial morphology. Taken together, these results are suggestive of impaired cortical connections and decreased synaptic efficiency in schizophrenia.
In a departure from the imaging and postmortem studies in the rest of the nanosymposium, Niran Okewole, of Nigeria’s Neuropsychiatric Hospital, Aro Abeokuta, examined the hand preference of patients with schizophrenia. Previous reports have suggested that there is an excess of left or mixed handedness in the illness (Upadhyay et al., 2004). Given a bias against left-handedness in African cultures, Okewole and colleagues examined whether the effect is present in a Nigerian sample. They observed an increase in left or mixed handedness in patients with schizophrenia compared to those with a mood disorder or healthy controls, suggesting that the effect in schizophrenia is not masked by culture. In addition, those schizophrenia patients who were left or mixed handed performed worse on a verbal fluency test than right-handed patients, indicative a possible relationship between handedness, schizophrenia, and verbal fluency.—Allison Curley.