1. Introduction

Anorexia nervosa (AN) is a particularly serious psychological problem which is characterised by extreme food restriction, a high-level anxiety of weight gain and a distorted cognition of body image. It is commonly seen among teenage and young females and associated with a high relapse rate. In recent years, it has become one of the major reasons causing mortality as a mental illness. Though conventional therapies such as cognitive-behavioral therapy (CBT) and nutritional rehabilitation provide some instructions for the treatment of AN, the underlying neurobiological basis still remains partially understood. However, thanks to the recent developments in neuroscience and molecular biology, elucidating the pathophysiological processes have been implemented to underpin this disorder, particularly in terms of neurotransmitter imbalances, hormonal dysregulation and energy metabolism [1].

Brain chemical systems have been proved to be abnormal due to AN in some research, especially those involving serotonin and dopamine. Firstly, altered serotonin transduction may increase the level of anxiety and result in more obsessive-compulsive behaviors. On the other hand, the blocking of dopamine pathways is the main reason why reward processing does not work and the anhedonia is deficient. Such neurochemical disorders would disturb eating behaviors and more seriously, make the treatment response hard to evaluate. Moreover, AN would cause hormonal imbalances including the decrease of leptin levels and elevated cortisol, which have been evidenced to be related with the abnormal appetite regulation and the disruption of energy homeostasis. All these biological findings lay a foundation for the development of targeted therapeutic strategies and reflect the need in further exploration into how these systems interact in the context of AN [1].

Actually, AN cannot be solely explained by neurobiological factors. Apart from this, psychological and cultural background in society should also be considered. Generally, AN patients often show high levels of perfectionism and rigid cognitive styles, which can be reflected by their exaggerated control of body weight and shape. Another culprit of these psychological features is social pressures like the idealism which equate slim figure with beauty and success. The combined action between all these factors may cause the happen and maintenance of AN and it is the main difference between it and other eating disorders. For example, while patients with bulimia nervosa (BN) and binge-eating disorder (BED) suffer from excessive food intake, BN is often accompanied with compensatory behaviors; AN, on the other hand, is primarily recognized by sustained caloric restriction. Similarly, though avoidant/restrictive food intake disorder (ARFID) also involves food limitation, there is a lack of the strong fear of weight gain and the significant body image disturbances. There two characters distinguish it with AN [2].

This review aims to comprehensively analyze recent advances of the AN pathophysiology. The main focus is the key neurobiological mechanisms which result in the disorder, such as neurotransmitter dysregulation, hormonal imbalances and metabolic disruptions. In addition to traditional psychological interventions, this paper would examine the potential of two new treatment strategies named novel pharmacological and neuromodulatory approaches in view of their possible contribution in addressing AN. By providing neurobiological evidence and considering psychological and sociological perspectives, this paper explores the interaction of genetic, neurobiological, psychological, and sociocultural factors in triggering and maintaining AN. It also examines whether psychological interventions can lead to more effective therapeutic outcomes for AN. Addressing these aspects is essential for developing precision treatments and ultimately improving patient recovery rates.

2. Risk factors for AN

As mentioned above, this disorder caused by an interplay of biological, psychological, and socio-cultural factors. Biologically, many studies indicate that there is a possibility between 50% and 80% that AN would be passed on to the next generation, which show a strong genetic contribution. From the perspective of neurotransmitter, its imbalance especially those involving serotonin and dopamine systems domain in the mood regulation and appetite of those vulnerable individuals with AN. The third major element - hormonal abnormalities such as dysregulation in leptin, cortisol, and sex hormones – worsen the clinical presentation by influencing appetite and stress responses [3].

On a psychological level, anxiety, perfectionism, and obsessive-compulsiveness all increase the risk of suffering from AN. Many victims are prone to develop a distortion of negative self-cognition including the underestimation of self-concept and self-value, which further lead to a phantom anxiety of self-image. The main reason for these early symptoms may be traumatic experiences and high expectations from families. Individual maladaptive coping mechanisms – disordered eating patterns – is thereby motivated unconsciously.

Another key factor is socio-cultural influences. Specifically, adolescents particularly females are under huge pressure and constantly brainwashed by the conventional beauty standard that emphasizes on thinness as well pervasive media representations of idealized bodies. More seriously, the risk is mounting when some families either overtly or subtly reinforce these standards, which enlarge the contradiction between the real self-image and the social expectation. The confluence of these factors underlines the need for multifaceted approaches in both research and treatment.

3. Neurobiological mechanisms

The neuroscience made great process in explaining the disorder (AN) and provided new insight. It has been proved that neural pathways are changed especially in terms of the reward system cognitive control circuits, and emotional regulation networks. Dysfunction in the reward circuitry—particularly in the ventral striatum—impedes the normal processing of rewarding stimulation. This impairment may leadto the reinforcement of restrictive eating behaviors. Since food consumption no longer provides expected joy and pleasure, patients may enhance the level of self-starvation trying to regain control over their reward processing [4].

Meanwhile, it is observed that individuals with AN show increasing activities in brain areas - like the prefrontal cortex- which are responsible for congnitive control. This kind of heightening control may underlie the extreme self-discipline in eating behaviors and enable patients to insist in restrictive diets regardless of physical uncomfort. Furthermore, anxiety and stress would exacerbate symptoms, and this is evidenced by the over-activity of amygdala, a region related to emotional processing. This kind of overactive cognitive control network creates a neurobiological environment in which the patient’s self-imposed restrictions are maintained.

Dysregulation of the hormonal system also contributes to the pathophysiology of AN. Low levels of the satiety hormone, leptin, and high levels of the stress hormone, cortisol, are commonly encountered. Reduced levels of leptin may blunt the normal pangs of hunger, facilitating restriction of food intake in the long term more easily. Concurrently, high levels of cortisol not only increase the stress response but also potentially alter the storage and metabolism of body fat, reinforcing the abnormal body concept and fear of weight gain that characterize AN. The interaction with the neurologic dysfunction reinforces the complex feedback loop in which biological disturbances maintain maladaptive eating behaviors.

4. Treatment strategies

Considering the complexity of AN, the therapeutic strategies need to be proportionally holistic, combining pharmacological, psychological, and novel interventional modalities.

4.1. Pharmacology intervention

While pharmacological treatment options for AN have emerged, they focus on the treatment of comorbid conditions including anxiety and depression rather than treating the core psychopathology of the disorder. SSRIsare commonly prescribed to balance mood and anxiety [5]. However, SSRIs appear to reduce some emotionally-weighted symptoms associated with anorexia but do nothing for the restoration and normalization of a healthy eating pattern. Likewise, atypical antipsychotics (e.g., olanzapine) have been shown to stimulate appetite and decrease anxiety. However, these medications have downsides: metabolic derangements and other toxicities can impact compliance and outcomes [5].

A novel area of nutritional research is the therapeutic application of the leptin molecule. As a means of reinstating the normal controls that govern hunger, leptin therapy may be able to counter the sustained suppression of hunger that characterizes AN. Clinical trials, however, are at an early stage, and there is still a lot to be learned about optimal dosing, long-term safety, and efficiency in patient populations.

4.2. Psychological interventions

Psychological treatments continue to be the cornerstone of AN management. It is widely employed to address the maladaptive thought patterns and cognitive distortions that fuel disordered eating. CBT techniques are designed to help patients identify and challenge irrational beliefs about body image and self-worth, gradually replacing them with more adaptive coping strategies [6].

Family-Based Therapy (FBT) represents another critical component of psychological intervention, particularly for adolescents [7]. FBT aims to involve the family unit in the recovery process, recognizing that familial support can be a powerful catalyst for change. By actively engaging family members in treatment, FBT helps to realign unhealthy dynamics and foster an environment that encourages recovery [7].

Motivational Interviewing (MI) is also gaining traction as a technique to enhance patient engagement and facilitate readiness to change. MI focuses on resolving ambivalence and building intrinsic motivation, which is essential for patients who are often resistant to altering deeply ingrained behaviors [8].

4.3. Emerging treatments

Recent years saw an increase in the research on new therapeutic modalities. Transcranial Magnetic Stimulation (TMS) is a non-invasive method to modify the circuits engaged in AN [9]. TMS, targeting specific brain locations that are engaged in reward and emotion regulation, has the promise to be an adjunctive therapy to supplement standard therapies.

Further, treatments to modify the microbiota in the gut are being researched. New evidence suggests the significance of the gut-brain axis in mood and behaviour control. Restoring the normal equilibrium of the bacteria in the gut using these treatments may indirectly improve metabolic and psychological factors, offering a new avenue for therapy in a disorder where traditional methods have been unsuccessful.

5. Discussion

Besides the significant advances that have been achieved in the pathophysiology of AN, several issues remain in research as well as in the clinic. One of the significant obstacles is the internal complexity of the disorder. The interplay of genetic, neurobiological, and socio-cultural factors creates a heterogeneous sample of patients, and it becomes difficult to develop standardized regimens that are universally effective. This heterogeneity is added to the fact that the majority of pharmacological treatments address only secondary symptoms, e.g., anxiety or depression, but not the primary pathological mechanisms of AN...

Another main concern is the lack of neurobiological models. Neuroimaging and hormonal assays have provided much information about the underlying mechanisms, but the in-time interaction of these factors during the disorder has not been fully understood. For instance, while increased cognitive control has been evidenced as a maintaining factor in restricting eating, whether this is due to neurobiological defect or just an adaptive response to starvation over the long term remains unclear. Similarly, there is still controversy over the contribution of imbalances in the neurotransmitters to the maintenance of disordered eating [10].

Clinically, personal shame and guilt together with the criticism to AN from the public are primary barriers and reasons why some patients avoid seeking treatment. This would exacerbate the severity of the disorder. Furthermore, the chronicity and high relapse rates of AN needs long-term and continued intervention. Despite the availability of therapies, their treatment results are inconsistent and easily relapse. All these call for a need for more specific and individualized treatments.

To solve these problems, the field more focus on precision medical models recently. And future research must aim at developing individualized intervention models integrating genetic, neurobiological, and psychosocial data. Tailored interventions to the patient's situation may allow clinicians to improve the influence of the intervention therefore bringing better long-term outcomes. In addition, the adoption of digital interventions such as telemedicine and mobile health applications brings higher possibilities to increase the engagement of patients and provide continuous monitoring outside of clinical settings.

In short, despite continuous progress, much more remains to be learned in knowing and curing AN. The reality being confronted today is that current treatments are only effective for some aspects of the disorder but cannot cure it in light of pathophysiology. Filling this gap will require joint effort by integrating neurobiological science and innovative therapeutic strategies. Only in this way can more sustainable and efficient outcomes be achieved to benefit those who suffer from this disabling disorder.

6. Conclusion

This paper has comprehensively examined AN in terms of neurobiological, psychological, and sociocultural perspectives, therefore offering an all-round understanding of the pathophysiological mechanisms of AN and possible therapeutic approaches. Also, the interaction of neurobiological disturbances, cognitive rigidity, and social pressures is discussed in terms of how they lead to sustained eating behavior disorder considering neurotransmitter dysregulation, hormonal imbalances, and reward-system dysfunctions.

In addition to those conventional treatments, some new therapies have also been evaluated in this review, pointing out the potential of novel interventions such as neuromodulation and microbiota-targeted therapies, as well as established psychological frameworks including CBT and FBT.

The findings emphasize that the triggers of AN are multiple, reiterating that no single factor can account for its onset or maintenance. Moreover, this review increases recognition of the consistency of the treatment and the disorder’s complexity. By integrating neurobiological data with psychological theory, the review analyses the possibility of developing individualized, precision-based therapies which may solve the key problem mentioned in the introduction considering the limited effectiveness of current treatments.

Nevertheless, some limitations must be acknowledged at the same time. Specifically, the dynamic interaction between various biological markers over time is still not fully understood and explained. Secondly, many proposed novel interventions are just in experimental phases. Additionally, existing research cannot be used to draw causal inferences resulted from the lack of real-time analysis of neurobiological activity during key behavioral episodes.

How to bridge these gaps should be the main focus of the future research both in longitudinal and multimodal dimensions to examine the evolution of genetic, neurochemical, and cognitive factors in different stages of AN. Digital health tools should also be included as a key point as they could improve patient engagement rate and provide continuous monitoring. Ultimately, an interdisciplinary approach is highly needed, which would not only improve treatment outcomes but also help the public fairly view the disorder itself and the timely seeking for medical-care.