Autism spectrum disorder (ASD) is a persistent deficit in social communication and interpersonal interactions in social, professional, or other settings, with symptoms such as repetitive body movements, limited and obsessive interests, and hypersensitivity or insensitivity to sensory stimuli (American Psychiatric Association, 2013). Previously thought to be a rare disorder, there have been numerous reports in recent years which indicate a higher prevalence than previously thought. In Denmark, 4.26% of males and 1.77% of females had ASD among those born between 1995–2016 (Dalsgaard et al., 2019). In Yokohama, Japan, the cumulative incidence of ASD at age 7 increased from 0.48% to 1.17–1.61% between 1988 and 1994–1996 (Honda et al., 2005). Furthermore, recent data showed that the prevalence of ASD in Japan may exceed 3% (Sasayama et al., 2021a; Sasayama et al., 2021b). ASD is associated with increased comorbidity of mood disorders such as depression and bipolar disorder, with high rates ranging from 11.2–36.1% (Ghaziuddin et al., 1998; Mouridsen et al., 2008). A previous study reported that fluoxetine was not effective for depressive symptoms in adults on the autistic spectrum (Williams et al., 2013). The development of evidence-based practices to treat depression in ASD is a new area of ongoing research (Pezzimenti et al., 2019). Although it is important to identify ASD comorbidity while treating depression, it is often difficult to diagnose ASD in adults because clinicians identify ASD symptoms underlying psychopathology in adulthood and distinguish ASD from other psychiatric disorders (Cochran et al., 2013). Furthermore, given the diagnostic complexity of overlapping symptoms, multimodal information collection is necessary to assess symptoms in multiple settings (Pezzimenti et al., 2019).

In a previous neuroimaging study, patients with ASD showed increased functional connectivity in the salience network and default mode network between the anterior insula and retrosplenial cortex and frontal pole, respectively. Patients with ASD also had increased functional connectivity in the dorsolateral prefrontal cortex to the retrosplenial cortex in the frontoparietal and default mode networks (Hogeveen et al., 2018). On the other hand, a resting-state functional neuroimaging study of individuals with depression showed impaired connectivity in the default mode network, central executive network, and salience network, as well as in the cerebellar network and thalamic network (Brakowski et al., 2017). In older patients with depression, regional homogeneity was reported to be decreased in the left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right anterior draft, and increased in the left posterior cerebellar lobe, left superior temporal gyrus, bilateral supplementary motor areas, and right postcentral gyrus (Liu et al., 2012a). There are reports of increased functional connectivity in the cerebellum and temporal lobe of adults with depression, and depression severity scores negatively correlated with functional connectivity between the bilateral lobule VIIb and the right superior frontal gyrus (Liu et al., 2012b). Furthermore, a previous study showed that functional connectivity in ASD was increased in the laterobasal parts and reduced in the centromedial and superficial parts of the amygdala (Kleinhans et al., 2016). They further showed that altered functional connectivity associated with the core features of ASD differed from that associated with depressive and anxiety symptoms in individuals with ASD (Kleinhans et al., 2016). However, no studies have clarified the differences in functional connectivity in patients exhibiting depression with and without ASD.

Early identification of ASD-related comorbidity in patients with depression using functional neuroimaging would be of high therapeutic utility because it would allow immediate treatment of ASD as well as depression. The aim of this study was to determine whether there is a difference in neuroimaging findings in patients diagnosed with depression depending on ASD comorbidity.