Is there disproportionate impairment in semantic or phonemic fluency in schizophrenia?

Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs < .79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits.     

Object activation in semantic memory from visual multimodal feature input.

The human brain's representation of objects has been proposed to exist as a network of coactivated neural regions present in multiple cognitive systems. However, it is not known if there is a region specific to the process of activating an integrated object representation in semantic memory from multimodal feature stimuli (e.g., picture-word). A previous study using word-word feature pairs as stimulus input showed that the left thalamus is integrally involved in object activation (Kraut, Kremen, Segal, et al., this issue). In the present study, participants were presented picture-word pairs that are features of objects, with the task being to decide if together they "activated" an object not explicitly presented (e.g., picture of a candle and the word "icing" activate the internal representation of a "cake"). For picture-word pairs that combine to elicit an object, signal change was detected in the ventral temporo-occipital regions, pre-SMA, left primary somatomotor cortex, both caudate nuclei, and the dorsal thalami bilaterally. These findings suggest that the left thalamus is engaged for either picture or word stimuli, but the right thalamus appears to be involved when picture stimuli are also presented with words in semantic object activation tasks. The somatomotor signal changes are likely secondary to activation of the semantic object representations from multimodal visual stimuli.     

Selective application of cervical spine radiography in alert victims of blunt trauma: a prospective study

Four hundred sixty-seven adult victims of blunt trauma undergoing cervical spine radiography (CSR) were prospectively studied to identify any clinical parameters which would aid in the selective application of CSR. Eight persons (1.7%), six of whom were alert and two who presented comatose, sustained cervical spine injuries. In this study, persons injured in falls demonstrated a statistically significant greater risk of cervical spine injury compared to those injured in motor vehicle accidents (p = 0.001). In alert trauma victims, a statistical correlation with cervical spine injury was noted for individuals who had complaints of neck discomfort (p = 0.028) and for patients who manifested tenderness to neck palpation (p = 0.000039). No cervical spine injury was noted in any alert, not intoxicated, neurologically intact patient who had no complaints of neck discomfort upon questioning or palpation. We conclude that alert trauma victims with no complaints of neck discomfort upon questioning and with no tenderness on neck palpation need not undergo CSR.     

Familial and sporadic schizophrenia. A simulation study of statistical power

The importance of genetic factors in schizophrenia is clear but the mechanism involved remains obscure. Etiological heterogeneity may be responsible. Recently there has been interest in a putative distinction between genetic and environmental forms of the illness based on a positive or negative family history of the disorder. Those with a positive family history are classified as 'familial' and are considered to be more likely to have the genetic form of the illness. Those with a negative family history are classified as 'sporadic' and considered more likely to have an environmental form of the illness. This paper reports the results of a Monte Carlo simulation study with varying rates of misclassification to determine the statistical power of comparisons between familial and sporadic groups. For a large sample (n = 175) statistical power was moderate to good for effect sizes greater than or equal to 1.0 standard deviation unit and positive predictive value of 0.3 or greater.     

Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein’s putative involvement in multiple developmental and stem cell maintenance pathways.Subject terms: Disease genetics, Diarrhoea     

Creutzfeldt-Jakob disease presenting with alien limb sign.

Creutzfeldt-Jakob disease is a fatal spongiform encephalopathy, which typically presents with a rapidly progressing dementia and additional neurological findings that can be quite variable and diverse. Here we report the unusual case of a patient who presented with left alien limb sign without overt cognitive impairment and was ultimately diagnosed with pathologically confirmed Creutzfeldt-Jakob disease.     

Development and aging of cortical thickness correspond to genetic organization patterns

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.There is a growing realization that events during development impact brain and cognition throughout the entire lifespan (1). For instance, the major portion of the relationship between cortical thickness and IQ in old age can be explained by childhood IQ (2), and genotype may explain a substantial part of the lifetime stability in intelligence (3). Effects of genes on the organization of the cortex have been shown in adults (4–6), but it is unknown whether and how regional differences in cortical development correspond to these regional genetic subdivisions.Although consensus has not been reached for the exact trajectories, cortical thickness as measured by MRI appears to decrease in childhood (7–12). The exact foundation for this thinning is not known, as MRI provides merely representations of the underlying neurobiology, and available histological data cannot with certainty be used to guide interpretations of MRI results. Although speculative, apparent thickness decrease may be grounded in factors such as synaptic pruning and intracortical myelination, although the link between established synaptic processes (13–15) and cortical thickness has not been empirically confirmed. After childhood, cortical thinning continues throughout the remainder of the lifespan, speculated to reflect neuronal shrinkage and reductions in number of spines and synapses (16), although similar to development, we lack data to support a direct connection between cortical thinning and specific neurobiological events.It has been demonstrated that genetic correlations between thickness in different surface locations can be used to parcellate the adult cortex into regions of maximal shared genetic influence (4). This result can be interpreted according to the hypothesis that genetically programmed neurodevelopmental events cause lasting impact on the organization of the cerebral cortex detectable decades later (4–6). Here we tested how developmental and lifespan changes fit the genetic organization of cortical thickness in a large longitudinal sample with 1,633 scans from 974 participants between 4.1 and 88.5 y of age, including 773 scans from children below 12 y Genetically based subdivisions of cortical thickness from an independent dataset of 406 twins (4) were applied to the data, yielding 12 separate regions under maximum control of shared genetic influences. We hypothesized that thickness in cortical regions with overlapping genetic architecture would show similar developmental and adult age change trajectories and dissimilar trajectories for regions with low genetic overlap.     

A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses.

Evidence for neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia, patients with chronic psychotic bipolar disorder and normal controls. Groups were comparable on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also relatively similar on age at onset and number of hospitalizations. Using multivariate analyses of variance with sex and parental SES as covariates (our primary analyses), patients with schizophrenia were significantly more impaired than controls on seven of eight neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on declarative verbal memory, and showed moderate-to-large effect size decrements on abstraction, perceptual-motor speed and vigilance. Results were not attenuated when IQ was controlled, which was significantly lower in patients with schizophrenia. Analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.