Differently different?: A commentary on the emerging social cognitive neuroscience of female autism.

Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males. This observed preponderance of males in autistic populations has served as a focussing framework in all spheres of autism-related issues, from recognition and diagnosis through to theoretical models and research agendas. One related issue is the near total absence of females in key research areas. For example, this paper reports a review of over 120 brain-imaging studies of social brain processes in autism that reveals that nearly 70% only included male participants or minimal numbers (just one or two) of females. Authors of such studies very rarely report that their cohorts are virtually female-free and discuss their findings as though applicable to all autistic individuals. The absence of females can be linked to exclusionary consequences of autism diagnostic procedures, which have mainly been developed on male-only cohorts. There is clear evidence that disproportionately large numbers of females do not meet diagnostic criteria and are then excluded from ongoing autism research. Another issue is a long-standing assumption that the female autism phenotype is broadly equivalent to that of the male autism phenotype. Thus, models derived from male-based studies could be applicable to females. However, it is now emerging that certain patterns of social behaviour may be very different in females. This includes a specific type of social behaviour called camouflaging or masking, linked to attempts to disguise autistic characteristics. With respect to research in the field of sex/gender cognitive neuroscience, there is emerging evidence of female differences in patterns of connectivity and/or activation in the social brain that are at odds with those reported in previous, male-only studies. Decades of research have excluded or overlooked females on the autistic spectrum, resulting in the construction of inaccurate and misleading cognitive neuroscience models, and missed opportunities to explore the brain bases of this highly complex condition. A note of warning needs to be sounded about inferences drawn from past research, but if future research addresses this problem of male bias, then a deeper understanding of autism as a whole, as well as in previously overlooked females, will start to emerge. Plain Language Summary: Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males, with oft-quoted ratios of 4M: 1F. This has been reflected in the development of diagnostic criteria for autism and, consequently, of measures of eligibility for autism research programmes, with females being (as is now emerging) disproportionately excluded. As outlined in this review, this issue has been particularly problematic in brain-based studies of autism. Many studies have only tested male autistic participants, or minimal numbers of autistic females. By default, sex differences were not examined. But the impression given by such research reports has commonly been that the findings would be applicable to all autistic individuals. Recent psychological and clinical research has shown that there are a significant number of autistic females who have been missed by traditional diagnostic practices. Their inclusion has increased their eligibility for autism research studies. With respect to brain research, it has become possible to devise studies with matched numbers of autistic females and males, and to replicate studies that have previously only tested males. Newly emerging findings from such studies are demonstrating that the 'robust' autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females. It will be necessary to exercise caution in drawing inferences from previous male-biased studies of the autistic brain. However, the identification and inclusion of previously excluded female autistic participants hopefully offers more accurate insights into this highly complex and heterogeneous condition. Highlights: Several decades of neuroimaging research into autism has been based almost entirely on males; even big data sets show strong evidence of male bias. There is clear evidence that autistic females are being excluded from the research process by failures in diagnostic practices that have been developed on male-biased cohorts. Models of autism which inform research protocols are based on male autism phenotypes; it appears to have been assumed that the substantially fewer females that are diagnosed will present with equivalent, if milder, patterns of autistic differences. Newly emerging findings from social cognitive neuroscience research studies investigating sex/gender differences in autistic behaviour and associated biological correlates are demonstrating that the 'robust' autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females. Autism research programmes should prioritise the exploration of sex/gender effects. [ABSTRACT FROM AUTHOR]