Gut-Brain Interaction Disorders and Anorexia Nervosa: Psychopathological Asset, Disgust, and Gastrointestinal Symptoms.

BACKGROUND: Gastrointestinal (GI) symptoms are very common in subjects with eating disorders (EDs). This study aimed to (a) investigate the prevalence of gut-brain interaction disorders (DGBIs) in anorexia nervosa (AN) patients, according to ROME IV criteria; and (b) explore AN psychopathological assets and disgust that might impact GI symptoms. METHODS: Thirty-eight female patients consecutively diagnosed with untreated AN (age 19.32 ± 5.59) in an outpatient clinic devoted to EDs underwent Eating Disorder Inventory-3 (EDI-3), Hospital Anxiety and Depression Scale (HADS), Social Phobia Anxiety Scale (SPAS), Body Uneasiness Test (BUT), and Disgust Scale (DS) questionnaires. The presence of DGBIs was evaluated and GI symptoms were assessed using a standardized intensity-frequency questionnaire. RESULTS: A total of 94.7% of our sample met the diagnostic criteria for functional dyspepsia (FD), of which 88.8% presented the postprandial distress syndrome (PDS) subtype and 41.6% presented the epigastric pain syndrome (EPS) subtype. In addition, 52.6% of the sample met the diagnostic criteria for irritable bowel syndrome (IBS), while for functional constipation (FC), prevalence reached 7.9%. All participants presented a pathological score on the disgust scale. Significant correlations were found between several GI symptoms and psychopathological asset and disgust. CONCLUSIONS: AN is a multifactorial disorder. It is necessary to implement studies with an integrated approach, taking into account DGBIs, as well as to monitor the emotional-cognitive structure that acts as a factor in maintaining the disorder.

Neurobiological Correlates Shared Between Obesity, BED and Food Addiction.

The ubiquity of the obesity condition in the United States, Europe and other regions with developed economies will associate to a significant adverse impact on public health. Numerous data indicate that social, behavioral, neuroendocrine, and metabolic factors may encourage compulsive eating behaviors thus increasing the risk of obesity. Several pathological conditions overlap with excess weight. Among the most common, there are binge eating disorder (BED) and food addiction (FA), which share several neurobiological and behavioral aspects with substance addictions. BED has many features in common with addictive behavior, such as loss of control and the need to frequently repeat the dysfunctional pattern despite negative consequences. The food addiction hypothesis assumes that exposure to highly palatable foods alters the reward circuits of the brain, resulting in a behavioral phenotype similar to substance addiction and facilitating dysfunctional eating behaviors, such as binge eating crises. In this review, over 100 publications, researched on MEDLINE from 2000 until march 2021, were included since they evaluate neuroendocrine changes, emotional homeostatic factors and the reward circuit, associating them with exposure to highly palatable foods, loss of control, the way we eat, the increase in impulsiveness and the inability to change eating behavior despite the negative consequences related to overweight and obesity. Finally, understanding the underlying neurobiological circuits of compulsive eating behaviors and food addiction could result in a great therapeutic potential for patients suffering from ailments nutrition and obesity.

Menstrual Disorders Related to Eating Disorders.

Eating Disorders (ED) are associated with multiple physical complications that strongly affect the physical health of these young and fragile patients and can also cause significant mortality, the highest among psychiatric pathologies. Among the various organic complications, albeit still little known, the gynecological implications, up to infertility, are very widespread. Both among adolescent and adult patients, gynecological symptoms can be very widespread and range from menstrual irregularities to amenorrhea, from vaginitis to ovarian polycystosis, up to complications during the gestational phase and in postpartum, in addition to the possible consequences on the unborn child. Among the most frequent and significant gynecological disorders in women with ED, there are menstrual irregularities that may occur with oligomenorrhea or even amenorrhea. This symptom, although no longer part of the DSM-5 diagnostic criteria for defining Anorexia Nervosa (AN), must be considered a very relevant event in the overall evaluation of young women and adolescents with eating disorders. Functional Hypothalamic Amenorrhea in ED patients is related to psychological distress, excessive exercise, disordered eating, or a combination of these factors which results in suppression of the hypothalamic- pituitary-ovarian axis, resulting in hypoestrogenism. The objective of this paper is to summarize the causes and the mechanism underlying the menstrual disorders and to provide a better understanding of the correlation between the reproductive system and the mechanisms that regulate food intake and eating habits. In addition, early recognition of risk factors for eating disorders for gynecological implications can help put more accurate assessments of patients to prevent potentially fatal complications. The importance of the involvement of specialist gynecologists in the multidisciplinary team that has to follow patients with eating disorders is also discussed.

Obesity and Its Multiple Clinical Implications between Inflammatory States and Gut Microbiotic Alterations.

Obesity is a chronic multifactorial disease that has become a serious health problem and is currently widespread over the world. It is, in fact, strongly associated with many other conditions, including insulin resistance, type 2 diabetes, cardiovascular and neurodegenerative diseases, the onset of different types of malignant tumors and alterations in reproductive function. According to the literature, obesity is characterized by a state of low-grade chronic inflammation, with a substantial increase in immune cells, specifically macrophage infiltrates in the adipose tissue which, in turn, secrete a succession of pro-inflammatory mediators. Furthermore, recent studies on microbiota have postulated new possible mechanisms of interaction between obesity and unbalanced nutrition with inflammation. This intestinal "superorganism" complex seems to influence not only the metabolic balance of the host but also the immune response, favoring a state of systemic inflammation and insulin resistance. This review summarizes the major evidence on the interactions between the gut microbiota, energetic metabolism and host immune system, all leading to a convergence of the fields of immunology, nutrients physiology and microbiota in the context of obesity and its possible clinical complications. Finally, possible therapeutic approaches aiming to rebalance the intestinal microbial ecosystem are evaluated to improve the alteration of inflammatory and metabolic states in obesity and related diseases.

Recent Advances in Treatment of Childhood Obesity.

Childhood obesity has assumed epidemic proportions and is currently one of the most widespread public health problems. Many are the factors involved in the pathogenesis of excess weight with interactions between genetic, environmental and biological factors and therefore, also the therapeutic approach must be multidisciplinary and multidimensional. In this review of the literature, we report the contiguity of childhood obesity with eating disorders and the importance of involving the family context in order to induce stable lifestyle changes, both in relation to dietary and nutritional habits, but also in increasing physical activity. Finally, among the therapeutic options, although for selected cases, pharmacotherapy and bariatric surgery can be used as treatment strategies.

Depression and Obesity: Analysis of Common Biomarkers.

Depression and obesity are very common pathologies. Both cause significant problems of both morbidity and mortality and have decisive impacts not only on the health and well-being of patients, but also on socioeconomic and health expenditure aspects. Many epidemiological studies, clinical studies and meta-analyses support the association between mood disorders and obesity in relationships to different conditions such as the severity of depression, the severity of obesity, gender, socioeconomic status, genetic susceptibility, environmental influences and adverse experiences of childhood. Currently, both depression and obesity are considered pathologies with a high-inflammatory impact; it is believed that several overlapping factors, such as the activation of the cortico-adrenal axis, the exaggerated and prolonged response of the innate immune system and proinflammatory cytokines to stress factors and pathogens-as well as alterations of the intestinal microbiota which promote intestinal permeability-can favor the expression of an increasingly proinflammatory phenotype that can be considered a key and common phenomenon between these two widespread pathologies. The purpose of this literature review is to evaluate the common and interacting mechanisms between depression and obesity.

Obesity: The New Global Epidemic Pharmacological Treatment, Opportunities and Limits for Personalized Therapy.

BACKGROUND: The increase in global obesity rates over the past three decades has been remarkable, a true epidemic, both in developed and in developing countries. The projections, based on current trends, suggest an increase in the prevalence of obesity at 60% in adult men, 40% in adult women and 25% in children in 2050. Given the limitations of lifestyle and surgery interventions bariatric, drug therapy approaches for the treatment of obesity, therefore become important options. AIM: The purpose of this review is a review of the literature, based on research on MEDLINE until 2019, on the possible pharmacological options in the treatment of obesity. RESULTS: Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. All the approved drugs showed, in the different studies, a weight reduction of at least 5%, compared to placebo, in 52 weeks of observation. Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. Liraglutide and naltrexone-bupropion had the lowest rates of therapy discontinuation due to adverse events. CONCLUSION: The drugs, associated with the standard diet and/or exercise protocols, represent a good therapeutic opportunity to allow not only weight loss but also to reduce the risk of developing diseases caused by obesity, particularly cardiovascular diseases, and to maintain the set objectives over time. However, future research on the pharmacological treatment of obesity should encourage greater personalization of therapy, given the differences in safety, efficacy and response to therapy, in the different subpopulations of patients with obesity.

Eating Disorders in Athletes: From Risk Management to Therapy.

BACKGROUND: Balanced sporting activity should be considered a resource in the treatment of eating disorders (ED), in particular of the BED and in obesity and, if conducted and guided by expert preparers and rehabilitators, in some forms of anorexia and in bulimia. OBJECTIVE: To assess the role of excessive physical activity, predominantly interfering with daily activities by ultimately resulting in greater energy consumption leading to weight loss, and study the diagnostic criteria of bulimia and anorexia nervosa. METHODS: A number of literature studies also report the presence of ED among athletes. A 2004 study reported that the prevalence of eating disorders in sports would be 13.5% compared to 4.5% of the control subjects. RESULTS: In general, nutrition is used as a tool for improving performance not only of athletes but also of technicians and coaches. But in the presence of factors of vulnerability towards ED, the tendency to manipulate the weight can result in an eating disorder or the so-called athletic anorexia or the RED-S. CONCLUSION: It is important to emphasize that not only do professional athletes suffer from it, but also good-looking amateurs and laypersons.

Gender Dysphoria, Eating Disorders and Body Image: An Overview.

BACKGROUND: Gender dysphoria is a clinical condition in which a state of inner suffering, stress and anxiety is detected when biological sex and a person's gender identity do not coincide. People who identify themselves as transgender people are more vulnerable and may have higher rates of dissatisfaction with their bodies which are often associated with a disorderly diet in an attempt to change the bodily characteristics of the genus of birth and, conversely, to accentuate the characteristics of the desired sexual identity. AIM: The purpose of this work is to examine the association between dissatisfaction with one's own body and eating and weight disorders in people with gender dysphoria. RESULTS: Gender dysphoria and eating disorders are characterized by a serious discomfort to the body and the body suffers in both conditions. The results of our study suggest that rates of pathological eating behaviors and symptoms related to a disordered diet are high in patients with gender dysphoria and that standard screening for these symptoms must be considered in both populations at the time of evaluation and during the course of the treatment. CONCLUSION: In light of this evidence, clinicians should always investigate issues related to sexuality and gender identity in patients with eating disorders, to develop more effective prevention measures and better strategies for therapeutic intervention.

Medical Complications in Anorexia and Bulimia Nervosa.

BACKGROUND AND OBJECTIVE: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and their variants are characterized by persistent alteration of eating behaviour, such as restricted intake or bingeing and purging, as well as excessive concerns about body shape and body weight. Purging behaviour may include self induced vomiting and/or abuse of laxatives, diuretics and physical hyperactivity. Unlike other psychiatric disorders, patients suffering from AN and BN have a high prevalence of many different medical complications, through the sequelae of undernutrition and purging, often with a serious impairment of health status and quality of life. This article describes the main diagnostic and clinical aspects of medical complications in AN and BN. RESULTS: The medical complications of ED are extremely variable and can occur with only modest biological and physical damage up to extremely serious and life-threatening conditions; the mortality rate of young subjects with AN is 4 - 11% with a risk of death about 12 times higher than that of subjects of the same age of the general population. The management of the medical-internship aspects of AN and BN is rightly placed within complex and articulated programs of interdisciplinary treatment with different levels of intensity of care (outpatient, semi-residential/residential, hospital in cases of emergency/medical and/or psychiatric emergency). CONCLUSION: the results of the investigations carried out, describe the functions of the various organs and apparatuses and the alterations detected, the possible complications and physiological adaptations to malnutrition.

Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders.

BACKGROUND AND OBJECTIVE: Eating Disorder (ED) is characterized by persistently and severely disturbed eating behaviours. They arise from a combination of long-standing behavioural, emotional, psychological, interpersonal, and social factors and result in insufficient nutrient ingestion and/or adsorption. The three main EDs are: anorexia nervosa, bulimia nervosa, and binge eating disorder. We review the role of peripheral endocannabinoids in eating behaviour. DISCUSSION: The neuronal pathways involved in feeding behaviours are closely related to catecholaminergic, serotoninergic and peptidergic systems. Accordingly, feeding is promoted by serotonin, dopamine, and prostaglandin and inhibited by neuropeptide Y, norepinephrine, GABA, and opioid peptides. The endocannabinoid system plays a role in EDs, and multiple lines of evidence indicate that the cannabinoid signalling system is a key modulatory factor of the activity in the brain areas involved in EDs as well as in reward processes. CONCLUSION: Besides their central role in controlling food behaviours, peripheral cannabinoids are also involved in regulating adipose tissue and insulin signalling as well as cell metabolism in peripheral tissues such as liver, pancreas, fatty tissue, and skeletal muscle. Altogether, these data indicate that peripheral cannabinoids can provide new therapeutic targets not only for EDs but also for metabolic disease.

Neuroendocrine and Metabolic Disorders in Bulimia Nervosa.

BACKGROUND AND OBJECTIVE: Bulimia nervosa, is an eating disorder characterized by excessive influence of weight and body shape on the levels of self-esteem, with pervasive feelings of failure and inadequacy. The eating is characterized by the presence of episodes of uncontrolled eating (Binge), during which the person ingests mass wide variety of foods and the feeling of not being able to stop eating. This review focuses on the metabolic and hormonal alterations in the in bulimia nervosa. METHODS: A literature search was conducted using the electronic database Medline and PubMed and with additional hand searches through the reference list obtained from the articles found. Journal were searched up to 2015. Inclusion criteria were: 1) full text available in English; 2) published in a peerreviewed journal and using the following keywords: neurotransmitters (AgRP, BDNF, αMSH, NP Y, endocannabinoids, adiponectin, CCK, ghrelin, GLP-1, insulin, leptin, PP, PYY), hormones (FSH, LH, estrogen, progesterone, testosterone) and bulimia nervosa, eating disorders. RESULTS: All data reported in the present review indicated that changes in the central and peripheral neuroendocrine equilibria may favor the onset and influence the course and prognosis of a DA. However, it is still questionable whether the alterations of the peptides and hormones regulating the mechanisms of eating behavior are the cause or consequence of a compromised diet. CONCLUSION: The results of the present review indicate that the altered balance of the various peptides or hormones can be relevant not only for the genesis and / or maintenance of altered dietary behaviors, but also for the development of specific psychopathological aspects in eating disorders.

[Seeking compulsory treatment as life-saving in the presence of eating disorders: a complex choice]. / Il trattamento sanitario obbligatorio come salvavita in presenza di disturbi dell'alimentazione: una scelta complessa.

Eating disorders (and especially anorexia nervosa) are associated with severe disability, poor quality of life and high mortality rate. Anorexia nervosa ranks among the main causes of death among young women. Despite physical and psycho-social impairment, patients suffering from anorexia nervosa do not recognize low body weight and extreme calorie restriction as a clinical problem and are ambivalent towards treatment. Some patients with anorexia nervosa refuse treatments though presenting severe medical complications and having a high mortality risk. Hence the need to evaluate when it could be appropriate to prescribe a compulsory treatment in the more complex cases who refuse interventions, deemed necessary for them. To date, the compulsory treatment in anorexia nervosa is still under debate: some authors take into account the negative impact on the therapeutic relationship, other authors consider it as a compassionate treatment or as life-saving therapy. Indeed, compulsory treatment for eating disorders must always be weighed very carefully because it is considered by law as the highest form of restriction of personal freedom. Political Institutions must provide a clear framework for the society and for professionals, while the health care services must face the problem of the adequacy of available resources (not only in terms of hospital beds but also of skilled professionals) compared to patients' needs, considering the organization and the integration of clinical services dedicated to the treatment of eating disorders.

Hyperprolactinemia Induced by Antipsychotics: From Diagnosis to Treatment Approach.

Schizophrenia is one of the most severe psychiatric diseases with a significant impact on the psychosocial functioning of the patients. People with schizophrenia are at risk to die prematurely because of their illness with their poor lifestyle contributing to the excess morbidity and higher mortality rate. In particular, lifestyle (e.g. poor diet, low rates of physical activity and increased likelihood to smoke cigarettes) predisposes them to poor physical health and comorbid medical diseases. In addition, the treatment of schizophrenia usually involves the long-term administration of antipsychotic drugs and some of these medications are implicated in the increased risk of metabolic and cardiovascular effects. The antipsychotic-induced hyperprolactinemia was ascertained for the first time by Kleinberg in 1971 and was considered for this treatment. Antipsychotics are the most common pharmacological agents which cause hyperprolactinemia The aim of this review is to describe PRL physiology, PRL biological effects and pathway to the diagnosis, causes, consequences of HPRL focusing on the antipsychotic effects on the PRL. We conducted a review of studies published between 1974 and December 2014. The search was performed using the following PubMed search terms: "Hyperprolactinemia" and "antipsychotic" and 827 papers were detected. The articles were examined and the overlapping or insufficiently clear works were excluded. Finally we chose 104 titles. We added to the selected articles additional articles, including 28 articles regarding the latest international guidelines, the pathophysiology of hyperprolactinemia and the various therapeutic choices.

Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study.

Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.

Flattened cortisol awakening response in chronic patients with schizophrenia onset after cannabis exposure.

Cannabis may play a causal role in the onset of some schizophrenia cases; however, the biological vulnerability that predisposes some individuals to develop schizophrenia after exposure to cannabis is not known. According to the diathesis-stress pathogenetic model, it is likely that the endogenous stress response system, including the hypothalamus-pituitary-adrenal (HPA) axis, could be involved. Therefore, we investigated the saliva cortisol awakening response (CAR) of 16 patients with schizophrenia onset after the exposure to cannabis (Can+) as compared to 12 patients with schizophrenia onset without cannabis exposure (Can-) and to 15 healthy controls. The CAR was assessed by collecting saliva samples at awakening and after 15, 30 and 60 min. As compared to healthy controls, Can+ schizophrenia patients exhibited significantly enhanced baseline saliva cortisol levels and a flattened CAR. No significant abnormality in both baseline cortisol levels and CAR was detected in Can- schizophrenia patients. These findings demonstrate a dysregulation of the HPA axis in chronic schizophrenic patients whose illness started after cannabis exposure but not in those with an illness onset without cannabis exposure. Further studies need to clarify whether this HPA dysregulation is a part of the biological background underlying the increased risk to schizophrenia after exposure to cannabis.

Antipsychotic drugs opposite to metabolic risk: neurotransmitters, neurohormonal and pharmacogenetic mechanisms underlying with weight gain and metabolic syndrome.

Important sources of metabolic diseases such as obesity and metabolic syndrome are significantly more prevalent in patients treated with antipsychotic drugs than the general population and they not only reduce the quality of life but also significantly reduce the life expectancy, being important risk factors for cardiovascular disease. The pathogenic mechanisms underlying these events are not entirely clear they are complex and multi-determined or not tied to a single defining event. In this review we examine the literature on the interactions of antipsychotic drugs with neurotransmitters in the brain, with pharmacogenetics hormones and peripheral mechanisms that may induce, albeit in different ways between different molecules, not only weight gain but also 'onset of major diseases such as diabetes, dyslipidemia and hypertension that are the basis of the metabolic syndrome. Today, the possible metabolic changes induced by various antipsychotic drugs and their major physical health consequences, are among the major concerns of clinicians and it is therefore necessary to monitor the main metabolic parameters to prevent or minimize any of these patients as well as the metabolism events associated with the use of antipsychotic drugs.

Agomelatine efficacy in the night eating syndrome.

Night eating syndrome (NES) is a nosographic entity included among the forms not otherwise specified (EDNOS) in eating disorders (ED) of the DSM IV. It is characterized by a reduced food intake during the day, evening hyperphagia, and nocturnal awakenings associated with conscious episodes of compulsive ingestion of food. Frequently, NES patients show significant psychopathology comorbidity with affective disorders. This paper describes a case report of an NES patient treated with agomelatine, an antidepressant analogue of melatonin, which acts by improving not only the mood but also by regulating sleep cycles and appetite. After three months of observation, the use of Agomelatine not only improved the mood of our NES patient (assessed in the HAM-D scores) but it was also able to reduce the night eating questionnaire, by both reducing the number of nocturnal awakenings with food intake, the time of snoring, the minutes of movement during night sleep (assessed at polysomnography), and the weight (-5.5 kg) and optimizing blood glucose and lipid profile. In our clinical case report, agomelatine was able both to reduce the NES symptoms and to significantly improve the mood of our NES patient without adverse side effects during the duration of treatment. Therefore, our case report supports the rationale for further studies on the use of Agomelatine in the NES treatment.

Night eating syndrome: an overview.

OBJECTIVES: The purpose of this review is to outline the nosographic characteristics of NES and the most reliable ethiopathogenetic theories in relation to the most recent evidence in the literature. KEY FINDINGS: The night eating syndrome (NES) is a disorder occurring at the stated time, that does not meet the criteria for any specific eating disorder. NES is characterized by a reduced feeding during the day, evening hyperphagia accompanied by frequent nocturnal awakenings associated with conscious episodes of compulsive ingestion of food and abnormal circadian rhythms of food and other neuroendocrine factors. Frequently it is associated with obesity and depressed mood. We highlight the therapeutic possibilities of some drugs, especially selective serotonin re-uptake inhibitors (SSRIs), which reduce the hyperactivity of the serotonin transporter in NES and significantly improve the clinical picture of this disease. CONCLUSIONS: Night eating syndrome is of importance clinically because of its association with obesity. The recognition and effective treatment of NES may be an increasingly important way to treat a subset of the obese population. Treatment of the syndrome, however, is still in its infancy. One clinical trial has reported efficacy with the SSRI sertraline. Other treatments, such as the anticonvulsant topiramate, phototherapy, and other SSRIs, may also offer future promise. Particularly useful would be studies involving brain scans (magnetic resonance imaging or single-photon emission computed tomography) of patients with NES compared with the healthy population, to investigate more thoroughly the possible alterations involved in the pathogenesis of NES.

Recent clinical aspects of hyperprolactinemia induced by antipsychotics.

This review will address the current understanding of the relationship between hyperprolactinemia and antipsychotic drugs. Hyperprolactinemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics. Release of PRL from lactotrope cells is influenced by several factors, such as stress, physical and sexual activity and food assumption. PRL secretion is regulated by hypothalamic-pituitary portal system and its homeostasis is the result of a complex balance between stimulating and inhibitory factors, both endogeneous and esogeneous. The main physiological control mechanism of secretion is played by the inhibitory action of dopamine. Conversely, among stimulation factors, serotonin is probably the main modulator of PRL release. An high number of drugs may cause PRL increase too, such as drugs that reduce dopaminergic functions at SNC level, or drugs with an antagonistic action towards dopaminergic receptors and those increasing serotonergic neurotransmission. Hyperprolactinemia is one of the most frequent endocrine pathologies of the hypothalamic-pituitary axis. Antipsychotics (AP) are the most common cause of druginduced hyperprolactinemia. Not all AP have the same impact on inducing hyperprolactinemia. In this review we will focus on the subdivision of AP in 'PRL-raising' (stimulators) and 'PRL-sparing' (sparers) and on their differences in inducing hyperprolactinemia. Finally we evaluated different complications in patients with antipsychotics induced hyperprolactinemia that may cause not only short-term side effects but also important systemic long-term effects. At the end of the review we finally report the possible options of treatment considering however that at present there are no ideal therapies or evaluations, and decisions have to be made on a case by case basis.