Altered language network activity in young people at familial high-risk for schizophrenia.

BACKGROUND: Abnormalities in language and language neural circuitry are observed in schizophrenia (SZ). Similar, but less pronounced language deficits are also seen in young first-degree relatives of people with SZ, who are at higher familial risk (FHR) for the disorder than the general population. The neural underpinnings of these deficits in people with FHR are unclear. METHODS: Participants were 43 people with FHR and 32 comparable controls. fMRI scans were collected while participants viewed associated and unrelated word pairs, and performed a lexical decision task. fMRI analyses conducted in SPM8 examined group differences in the modulation of hemodynamic activity by semantic association. RESULTS: There were no group differences in demographics, IQ or behavioral semantic priming, but FHR participants had more schizotypal traits than controls. Controls exhibited the expected suppression of hemodynamic activity to associated versus unrelated word pairs. Compared to controls, FHR participants showed an opposite pattern of hemodynamic modulation to associated versus unrelated word pairs, in the left inferior frontal gyrus (IFG), right superior and middle temporal gyrus (STG) and the left cerebellum. Group differences in activation were significant, FWE-corrected for multiple comparisons (p<0.05). Activity within the IFG during the unrelated condition predicted schizotypal symptoms in FHR participants. CONCLUSIONS: FHR for SZ is associated with abnormally increased neural activity to semantic associates within an inferior frontal/temporal network. This might increase the risk of developing unusual ideas, perceptions and disorganized language that characterize schizotypal traits, potentially predicting which individuals are at greater risk to develop a psychotic disorder.

Decreased axial diffusivity within language connections: a possible biomarker of schizophrenia risk.

Siblings of patients diagnosed with schizophrenia are at elevated risk for developing this disorder. The nature of such risk associated with brain abnormalities, and whether such abnormalities are similar to those observed in schizophrenia, remain unclear. Deficits in language processing are frequently reported in increased risk populations. Interestingly, white matter pathology involving fronto-temporal language pathways, including arcuate fasciculus (AF), uncinate fasciculus (UF), and inferior occipitofrontal fasciculus (IOFF), are frequently reported in schizophrenia. In this study, high spatial and directional resolution diffusion MRI data was obtained on a 3T magnet from 33 subjects with increased familial risk for developing schizophrenia, and 28 control subjects. Diffusion tractography was performed to measure white matter integrity within AF, UF, and IOFF. To understand these abnormalities, Fractional Anisotropy (FA, a measure of tract integrity) and Trace (a measure of overall diffusion), were combined with more specific measures of axial diffusivity (AX, a putative measure of axonal integrity) and radial diffusivity (RD, a putative measure of myelin integrity). Results revealed a significant decrease in Trace within IOFF, and a significant decrease in AX in all tracts. FA and RD anomalies, frequently reported in schizophrenia, were not observed. Moreover, AX group effect was modulated by age, with increased risk subjects demonstrating a deviation from normal maturation trajectory. Findings suggest that familial risk for schizophrenia may be associated with abnormalities in axonal rather than myelin integrity, and possibly associated with disruptions in normal brain maturation. AX should be considered a possible biomarker of risk for developing schizophrenia.

Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia.

The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations.

Melengestrol acetate and norgestomet for the induction of synchronized estrus in seasonally anovular ewes.

Two commercially available progestogen products for cattle, melengestrol acetate (MGA) and norgestomet (SMB), were evaluated for their ability to induce synchronized estrus in anovulatory ewes. Seasonally anestrous ewes (n = 232) were randomly assigned to one of seven treatments: 1) control (C); 2) MGA only (OMGA; .3 mg of MGA/d); 3) MGA+zeranol (RMGA; 2.5 mg of zeranol); 4) MGA+PG-600 (PMGA; 400 IU of PMSG + 200 IU of hCG in a 5-mL dose); 5) SMB only (OSMB); 6) SMB + zeranol (RSMB); and 7) SMB + PG-600 (PSMB). Treatments were initiated 10 d before breeding. Immediately preceding progestogen treatment, RMGA and RSMB ewes were given a single i.m. injection of zeranol. Concomitant to progestogen removal, PMGA and PSMB ewes were given a single i.m. injection of PG-600. On May 4, 1992, all treatment groups were combined into one breeding group for a 30-d breeding period. Mating at synchronized estrus was greater (P < .001) for progestogen-treated ewes. Within progestogen treatments, more (P < .001) SMB ewes than MGA ewes were marked within the first 5 d of breeding. Overall, there were no treatment differences in estrus response for the 30-d breeding period. Progestogen-treated ewes had a shorter (P < .001) mean interval from ram introduction to lambing. Fertility and prolificacy were not different for C, MGA, or SMB ewes. Ewes primed with zeranol before MGA or SMB treatment had fertility and intervals from ram introduction to lambing similar to those of ewes receiving an injection of PG-600 after progestogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)