Table 5 Reports dealing with neurological pathways and their major finding

Red flags/screening

Genetic neurological pathways

Bhattacharya A, 2020 [15]

Some neuropsychiatric disorders tend to be more associated with AN, such as oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety disorders, obsessive compulsiveness, depressive symptoms, and suicidal ideation. Prior to puberty, the impact of genetics on developing an ED is 50% in males and 0% in females; at puberty it increases to 50% in females with puberty.

As the insula helps to integrate and regulate autonomic, affective, and sensory systems, researchers proposed a theory of insular dysfunction playing an etiologic role in AN.

Red flags/screening

Environment neurological pathways

McAdams CJ, 2022 [18]

Self-esteem and socializing problems are associated with ED symptoms during adolescence. Social stressors often concur with ED symptom onset. Common stressors are bullying about shape/weight/appearance. In Fijian adolescents, social pressures from a changing society correlate to body size concerns and ED. Adolescents with AN presented reduced activation in the superior temporal sulcus. Adolescents who recovered from AN had no whole-brain differences, and less activation in the precuneus one year later. Study in adolescents with AN showed reduced processing in the social condition in the medial prefrontal cortex and less activation in this region at baseline was associated with worse outcomes a year later. In adolescents with AN, dorsolateral prefrontal cortex activation at baseline was related to increased amygdala.

Red flags/screening

Genetics neurological pathways

Grammatikopoulou, 2023 [22]

Children and adolescents with autoimmune or autoinflammatory diseases are at greater risk (HR: 37%) of developing AN. Specific brain-reactive autoantibodies in juvenile SLE correlate with neuropsychiatric disorders. Twin studies indicated heritability. Brain scans of affected persons and genome-wide association studies pointed to the fact that AN is primarily observed in families with perfectionist, obsessive, and competitive traits.

Neurological pathways

Lucherini Angeletti L, 2022 [45]

Abnormalities in the feeling of bodily sensations, namely interoception, may play a role in the pathogenesis of AN. An alteration of the neural interoceptive-processing regions, particularly between subcortical and anterior midline cortical regions, suggest how interoceptive deficits may play a role in altered emotional experience and body-objectification.

In adolescents with AN, resting state was investigated showing almost total hypoconnectivity compared to controls, with decreased activity between subcortical–cortical midline structure. At rest, four subcortical regions (i.e., thalamus, caudate and cerebellum) show decreased resting-state functional connectivity” with cortical areas.

Neurological pathways

Mason TB, 2021 [46]

Adolescent AN showed lower activation in the striatum, frontal and temporal areas for negative images and in precuneus and hippocampus for positive images. Adolescent AN showed more activation in the medial prefrontal gyrus than controls when viewing neutral and positive images and in the cerebellum for negative images.

Neurological pathways

Kot E, 2020

[47]

Considering that sweet pleasantness was lower in adolescents with AN compared with controls and that patients’ gyrus rectus volume, in the frontal lobe, was negatively related to sweet pleasantness rating, the authors suggested that enlarged orbitofrontal cortex could be directly involved in food avoidance in adolescents with AN.

Neurological pathways

Stedal K, 2022 [48]

A meta-analysis on 665 adolescents affected by AN demonstrated a significant difference with controls for the cognitive domains of memory, working memory and visuospatial abilities, revealing a small cognitive underperformance in children and adolescents with AN, compared to controls. A significant effect of age also emerged, revealing that older participants had poorer neuropsychological test performance.

Neurological pathways

Keeler J, 2020 [49]

The scoping review focuses on hippocampus, a structure associated with memory, learning, visuospatial processes, and food intake. It highlights that adolescents with AN have a reduction in hippocampal volume and in all hippocampal subfields apart from the fissure. There is no agreement in literature on normalization in hippocampal volume, after weight recovery.

Neurological pathways

Kappou K, 2021 [50]

When comparing studies conducted in teens to those in adults, greater atrophy in AN adolescent hippocampus compared to adults and resting-state functional alterations. Specific brain regions such as the insula and parietal cortex appear to be consistently affected in young patients, suggesting their potential role in the disease pathophysiology.

Neurological pathways

Iorio Morin C, 2022 [51]

Magnetoencephalography, providing noninvasive measurements of fluctuations in the excitability of neuronal populations, has a potential role in delineating normal and abnormal brain dynamics and in understanding the pathological oscillatory activity that underline disorders including AN in which alpha- and beta-band dysregulation was found.

Neurological pathways

Berchio C, 2022 [52]

A reduced function of neuronal circuits involved in action had been found in AD adolescents, leading to behavioral deficits.

Studies on body and face perception indicate that adolescents with AN process bodies by focusing on local information (i.e., details) and faces by focusing on global information (paying less attention to details/emotional expressions). Brain waves studied in adolescents with AN were consistent with an increased theta activity in parietal-occipital regions after weight restoration, associated with decreased emotional distress. Findings on theta abnormalities appear consistent with evidence in adults with AN and may indicate that adolescents with AN show a different maturational profile on theta waves, reflecting a reduced regulation of top-down control processes.

Body mass index is positively linked with memory-related neural responses but negatively with neural substrates of inhibitory control. Depressive symptomatology is negatively associated with markers of attention and memory in AN.