Andrew C. Stanfield

Deficits in facial, body movement and vocal emotional processing in autism spectrum disorders

BACKGROUNDnPrevious behavioural and neuroimaging studies of emotion processing in autistic spectrum disorder (ASD) have focused on the use of facial stimuli. To date, however, no studies have examined emotion processing in autism across a broad range of social signals.nnnMETHODnThis study addressed this issue by investigating emotion processing in a group of 23 adults with ASD and 23 age- and gender-matched controls. Recognition of basic emotions (happiness, sadness, anger, disgust and fear) was assessed from facial, body movement and vocal stimuli. The ability to make social judgements (such as approachability) from facial stimuli was also investigated.nnnRESULTSnSignificant deficits in emotion recognition were found in the ASD group relative to the control group across all stimulus domains (faces, body movements and voices). These deficits were seen across a range of emotions. The ASD group were also impaired in making social judgements compared to the control group and this correlated with impairments in basic emotion recognition.nnnCONCLUSIONSnThis study demonstrates that there are significant and broad-ranging deficits in emotion processing in ASD present across a range of stimulus domains and in the auditory and visual modality; they cannot therefore be accounted for simply in terms of impairments in face processing or in the visual modality alone. These results identify a core deficit affecting the processing of a wide range of emotional information in ASD, which contributes to the impairments in social function seen in people with this condition.

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia

Objective:u2002 We sought to address whether dorsal or ventral prefrontal gyrification is abnormal in bipolar disorder and to determine its diagnostic specificity and cognitive associations.

Orbitofrontal morphology in people at high risk of developing schizophrenia

BACKGROUNDnAbnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.nnnMETHODSnHundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.nnnRESULTSnWe refined Chiavaras classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.nnnCONCLUSIONSnOur results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.

Hypofrontality in subjects at high genetic risk of schizophrenia with depressive symptoms

BACKGROUNDnSubjects at high risk of schizophrenia for genetic reasons were found to demonstrate increased levels of depressive symptoms compared to controls. The current study sought to investigate the neural correlates of depression in these subjects. We hypothesised abnormal activation of dorsolateral prefrontal regions in those at high risk with depression.nnnMETHODSnDepression was rated according to DSM-IV criteria. FMRI data was available from 90 high risk subjects, comprising 78 not depressed (HRD-) and 12 depressed (HRD+) subjects. Activation during the Hayling Sentence Completion Task was compared to 25 healthy control subjects without depression.nnnRESULTSnThe HRD+ group demonstrated reduced activation of the right middle/superior frontal gyrus compared to both healthy controls and the HRD- group. Increased left superior temporal gyrus activation was also found in the HRD+ group versus the HRD- group. These results survived controlling for the presence of positive psychotic symptoms at the time of the scan.nnnCONCLUSIONnReduced activation of dorsolateral prefrontal regions, widely reported in established schizophrenia and seen here in people at high familial risk with depressive features, may be related to the presence of affective symptoms of the disorder rather than to the presence of positive psychotic symptoms. Since studies have indicated that depressive symptoms antecede illness, these findings may be relevant to the early features of developing psychosis.

Amygdala volume in a population with special educational needs at high risk of schizophrenia.

BACKGROUNDnThe mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia.nnnMETHODnAssessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated.nnnRESULTSnRight amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p=0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p<0.05), but not in either control group.nnnCONCLUSIONSnIntellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis.

Anterior cingulate morphology in people at genetic high-risk of schizophrenia.

BACKGROUNDnMorphological abnormalities of the anterior cingulate (AC) occur in patients with schizophrenia and in symptomatic high-risk individuals, and may be predictive of subsequent psychosis. We investigated AC sulcal morphology in the Edinburgh High Risk Study cohort to see if such abnormalities are evident and predict psychosis in patients relatives. We also investigated the association of the cingulate sulcus (CS) and paracingulate sulcus (PCS) variants with intelligence quotient (IQ).nnnPATIENTS AND METHODSnWe compared cingulate and paracingulate sulcal anatomy, using reliable standardised measurements, blind to group membership, in those at high genetic risk (n=146), first episode patients (n=34) and healthy controls (n=36); and compared high-risk subjects who did (n=17) or did not develop schizophrenia.nnnRESULTSnInterruptions of the cingulate sulcus were more common in high-risk individuals and in those with schizophrenia, in both hemispheres, compared to controls. When separated by gender, these results were only present in males in the left hemisphere and only in females in the right hemisphere. A well-formed paracingulate sulcus was less common in high-risk participants and patients with schizophrenia, compared to controls; but this association was only present in males. These morphological variants of the paracingulate sulcus and the continuous cingulate sulcus were also associated with the higher IQ in male high-risk individuals.nnnCONCLUSIONSnAn interrupted cingulate sulcus pattern in both males and females and paracingulate morphology in males are associated with increased genetic risk of schizophrenia. Associations between cingulate and paracingulate morphology and premorbid IQ scores provide evidence that intellectual ability could be related to particular cytoarchitectural brain regions. Given that these sulci develop in early fetal life, such findings presumably reflect early neurodevelopmental abnormalities of genetic origin, although environmental effects and interactions cannot be ruled out.

Dissociation of brain activation in autism and schizotypal personality disorder during social judgements

Abstract Background There are overlaps between autism and schizophrenia but these are particularly pronounced, especially in social domains, for higher functioning individuals with autism spectrum disorders (ASD) or schizotypal personality disorder (SPD). It is not known whether these overlapping social deficits result from shared or distinct brain mechanisms. We therefore compared social cognition in ASD and SPD using functional magnetic resonance imaging (fMRI). Methods Twenty-one individuals with SPD, 28 with ASD and 33 controls were compared with respect to clinical symptoms using the Positive and Negative Syndrome Scale; social cognition, using a social judgment task and Ekman 60 faces task; and brain activation using an fMRI task of social judgment. Results The ASD and SPD groups showed few differences in symptoms or social cognition. However, fMRI showed that, compared to ASD, the SPD group showed significantly greater activation during social compared to gender judgments in the amygdala and 3 clusters: right posterior cerebellum, extending into fusiform and inferior temporal gyri; left posterior cerebellum; and left intraparietal sulcus extending through medial portions of the temporal gyri into the fusiform gyrus (all P < .05 family-wise error corrected). Control activations lay between the ASD and SPD groups. Conclusions Although social cognitive deficits in ASD and SPD appear superficially similar they are the result of different brain mechanisms. These findings have implications for therapeutic interventions targeted at social dysfunction in these conditions.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Endocrine Dysfunction in Female FMR1 Premutation Carriers: Characteristics and Association with Ill Health

Female FMR1 premutation carriers (PMC) have been suggested to be at greater risk of ill health, in particular endocrine dysfunction, compared to the general population. We set out to review the literature relating to endocrine dysfunction, including premature ovarian insufficiency (POI), in female PMCs, and then to consider whether endocrine dysfunction in itself may be predictive of other illnesses in female PMCs. A systematic review and pilot data from a semi-structured health questionnaire were used. Medline, Embase, and PsycInfo were searched for papers concerning PMCs and endocrine dysfunction. For the pilot study, self-reported diagnoses in females were compared between PMCs with endocrine dysfunction (n = 18), PMCs without endocrine dysfunction (n = 14), and individuals without the premutation (n = 15). Twenty-nine papers were identified in the review; the majority concerned POI and reduced fertility, which are consistently found to be more common in PMCs than controls. There was some evidence that thyroid dysfunction may occur more frequently in subgroups of PMCs and that those with endocrine difficulties have poorer health than those without. In the pilot study, PMCs with endocrine problems reported higher levels of fibromyalgia (p = 0.03), tremor (p = 0.03), headache (p = 0.01) and obsessive–compulsive disorder (p = 0.009) than either comparison group. Further larger scale research is warranted to determine whether female PMCs are at risk of endocrine disorders other than those associated with reproduction and whether endocrine dysfunction identifies a high-risk group for the presence of other health conditions.