BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II - RADIATION CEREBRO/OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA II ­ RADIATsIINI TsEREBROOFTAL'MOLOGIChNI EFEKTY U DITEI, OSIB, EKSPONOVANYKh VNUTRIShN'O/UTROBNO, ASTRONAVTIV TA INTERVENTsIINYKh RADIOLOGIV.

BACKGROUND: Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis¼. OBJECTIVE: The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists. MATERIALS AND METHODS: The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications. RESULTS: Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital - after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology - cognitivedeficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, andcataracts, as well as early atherosclerosis and accelerated aging. CONCLUSIONS: Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. Part І. THE CONSEQUENCES OF IRRADIATION OF THE PARTICIPANTS OF THE LIQUIDATION OF THE CHORNOBYL ACCIDENT. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa. Chastyna I. TsEREBROOFTAL'MOLOGIChNI EFEKTY OPROMINENNIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES.

BACKGROUND: Exposure to ionizing radiation could affect the brain and eyes leading to cognitive and vision impairment, behavior disorders and performance decrement during professional irradiation at medical radiology, includinginterventional radiological procedures, long-term space flights, and radiation accidents. OBJECTIVE: The objective was to analyze the current experimental, epidemiological, and clinical data on the radiation cerebro-ophthalmic effects. MATERIALS AND METHODS: In our analytical review peer-reviewed publications via the bibliographic and scientometric bases PubMed / MEDLINE, Scopus, Web of Science, and selected papers from the library catalog of NRCRM - theleading institution in the field of studying the medical effects of ionizing radiation - were used. RESULTS: The probable radiation-induced cerebro-ophthalmic effects in human adults comprise radiation cataracts,radiation glaucoma, radiation-induced optic neuropathy, retinopathies, angiopathies as well as specific neurocognitive deficit in the various neuropsychiatric pathology including cerebrovascular pathology and neurodegenerativediseases. Specific attention is paid to the likely stochastic nature of many of those effects. Those prenatally and inchildhood exposed are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. CONCLUSIONS: The experimental, clinical, epidemiological, anatomical and pathophysiological rationale for visualsystem and central nervous system (CNS) radiosensitivity is given. The necessity for further international studieswith adequate dosimetric support and the follow-up medical and biophysical monitoring of high radiation riskcohorts is justified. The first part of the study currently being published presents the results of the study of theeffects of irradiation in the participants of emergency works at the Chornobyl Nuclear Power Plant (ChNPP).

Subthreshold Autism Spectrum in a Patient with Anorexia Nervosa and Behçet's Syndrome.

Recently, increasing research stressed the presence of subthreshold autistic traits in patients with other psychiatric conditions. In this framework, a significant relationship between anorexia nervosa (AN) and the autism spectrum has been frequently reported, in particular among female samples, to the point that AN has been hypothesized to be a female phenotype of autism spectrum disorder (ASD). On the other hand, among subjects with ASD has been reported a higher prevalence of immune diseases and altered immune functions. While these reports seem to support an association between neurodevelopmental and immune system alterations in ASD, the relationship between the immune system and the broader autism spectrum, including its subthreshold manifestations, remains poorly investigated. In this report, we described the presence of autistic traits in a male inpatient with AN and separation anxiety disorder, who also show a diagnosis of Behçet's syndrome (BS). This case seems to further stress the association between AN and the autism spectrum, which may not be limited to the female gender. Moreover, it further suggests a deeper link between neurodevelopmental and immune system alterations. Implications are discussed in light of the more recent neurobiological and psychopathological hypothesis about the autism spectrum.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS: Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age

Comorbidity, age of onset and suicidality in obsessive-compulsive disorder (OCD): An international collaboration.

OBJECTIVES: To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. METHODS: Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. RESULTS: Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. CONCLUSIONS: In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

Ionizing radiation: brain effects and related neuropsychiatric manifestations. / IONIZUIuChA RADIATsIIa: VPLYV NA GOLOVNYY̆ MOZOK TA NEY̆ROPSYKhIATRYChNI PROIaVY.

Recently, an increasing interest has been directed towards the investigation of brain effects of ionizing radiation (IR), as it is now evident that, depending on the doses, the damages character and severity, as well as clinical man ifestations are different. They are generally considered to be the result of a blending of atherosclerotic, cardiovas cular, cerebrovascular and neurodegenerative processes. Further, an ongoing debate has been opened on the pos sible brain abnormalities following medical radiation from X ray in interventional radiology and nuclear medicine procedures that would involve both patients and medical workers. The aim of the present paper is to summarize literature data on brain effects of IR exposure, with a special focus on those gathered by some of the authors after the Chornobyl nuclear plant disaster, and how they can be related to the pathophysiology of different neuropsy chiatric disorders.

Problems following hippocampal irradiation in interventional radiologists - doses and potential effects: a Monte Carlo simulation. / PROBLEMY VNASLIDOK OPROMINENNIa GIPOKAMPA INTERVENTsIYNYKh RADIOLOGIV - DOZOVI NAVANTAZhENNIa TA YMOVIRNI EFEKTY: MODELIuVANNIa METODOM MONTE KARLO.

OBJECTIVE: This study aimed at investigating radiation exposure of hippocampus in interventional medical profes sionals irradiated in the operating room, and to compare doses in the hippocampus with the effective dose (protec tion quantity), as well as with the doses measured by individual dosimeter, in order to estimate probability of reach ing levels of radiation induced cognitive and other neuropsychiatric alterations during their working career, through a Monte Carlo simulation. MATERIALS AND METHODS: A Monte Carlo simulation of hippocampal exposure was used by means of a hybrid voxel mathematical phantom of a doctor irradiated in typical angiographic projections and energy spectra inherent to interventional cardiology procedures. RESULTS: The results showed that cranial irradiation was very heterogeneous and depended on the projection: doses of left and right hippocampi may be different up to a factor of 2.5; under certain conditions, the dose of the left hippocampus may be twice the effective dose, estimated by conventional double dosimetry algorithm. CONCLUSIONS: The professional span doses of the irradiated hippocampus may overcome the threshold able to pro voke possible cognitive and emotional behavioral impairment. Therefore, in depth studies of the effects of brain irradiation in occupationally exposed interventional medical personnel appear urgently needed and crucial.

Mice lacking the Parkinson's related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect.

Non-motor symptoms in Parkinson's disease (PD) have been often described at different stages of the disease but they are poorly understood. We observed specific phenotypes related to these symptoms in mice lacking the PD-associated GPR37/PAEL receptor. GPR37 is an orphan G-protein-coupled receptor highly expressed in the mammalian central nervous system. It is a substrate of parkin and it is involved in the pathogenesis of PD. GPR37 interacts with the dopamine transporter (DAT), modulating nigro-striatal dopaminergic signaling and behavioral responses to amphetamine and cocaine. GPR37 knockout (KO) mice are resistant to MPTP and exhibit several motor behavioral abnormalities related to altered dopaminergic system function. To evaluate non-motor behavioral domains, adult and aged, male and female GPR37 KO mice and their wild-type (WT) littermates were analyzed in a series of cross-sectional studies. Aged GPR37 KO female mice showed mild improvements in olfactory function, while anxiety and depression-like behaviors appeared to be significantly increased. A reduction of the startle response to acoustic stimuli was observed only in adult GPR37 KO mice of both genders. Furthermore, HPLC analysis of major neurotransmitter levels revealed gender differences in the striatum, hippocampus and olfactory bulb of mutant mice. The absence of GPR37 receptor could have a neuroprotective effect in an age and gender-dependent manner, and the study of this receptor could be valuable in the search for novel therapeutic targets.

The relationship between epilepsy and depression: an update.

Several population-based studies and clinical data suggest the presence of strict relationships between epilepsy and depression. The incidence of depressive symptoms in patients with epilepsy is significantly higher than in the general population or in patients with other neurological disorders or chronic diseases, as shown by the majority, albeit not all, findings. Even the rate of suicide is higher in epileptic patients than in the general population. Such observations suggest the existence of common neurobiological substrates involving hyperactivity of the hypothalamus-pituitary-adrenal axis, as well as disturbances of different neurotransmitter systems, particularly serotonin and norepinephrine. The aim of this paper is to review the current literature on the prevalence, clinical manifestations and etiology of depression in epilepsy, with a particular focus on the possible pathophysiological mechanisms shared by the two conditions. In spite of the large amount of data, several questions remain open and further studies are necessary to explore more thoroughly the complex and bidirectional relationships between epilepsy and depression.

Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects.

BACKGROUND: Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. AIM: The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non-mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. RESULTS: The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. CONCLUSIONS: The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

Psychiatric disorders and mitochondrial dysfunctions.

BACKGROUND: Mitochondria play a key role in the production of the cell energy. The final product of this process is adenosine triphosphate (ATP), used as a source of chemical energy. Besides this major role, mithocondria have been shown to be involved in other functions, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. The aim of this paper is to highlight the relationships between psychiatric disorders, especially schizophrenia, bipolar disorder (BD), autism, attention deficit-hyperactivity disorder (ADHD) and Alzheimer's dementia. RESULTS: The review of the available literature indicate that different mitochondrial dysfunctions may accompany and/or be part of the clinical picture of some neuropsychiatric disorders. CONCLUSIONS: Different data would indicate that mitochondrial dysfunctions may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in the cell energy metabolism. Moreover, they would greatly contribute to the process of neural apoptosis that should be at the basis of neurodegenerative disorders, such as schizophrenia, Alzheimer's dementia and the most severe forms of BD. In addition, data are available that mithocondrial abnormalities are present also in developmental disorders, such as autism and ADHD, although the studies aiming at elucidating the role of mithocondria in the onset and pathophysiology of all these conditions should be considered preliminary. In any case, taken together, these scattered findings would suggest novel drugs targeting protecting mitochondria from oxidative stress.

Cognitive, psychological and psychiatric effects of ionizing radiation exposure.

Radiation exposure leads to an increased risk for cancer and, possibly, additional ill-defined non-cancer risk, including atherosclerotic, cardiovascular, cerebro-vascular and neurodegenerative effects. Studies of brain irradiation in animals and humans provide evidence of apoptosis, neuro-inflammation, loss of oligo-dendrocytes precursors and myelin sheaths, and irreversible damage to the neural stem compartment with long-term impairment of adult neurogenesis. With the present paper we aim to present a comprehensive review on brain effects of radiation exposure, with a special focus on its impact on cognitive processes and psychological functions, as well as on their possible role in the pathophysiology of different psychiatric disorders.

Latest advancements in the pharmacological treatment of binge eating disorder.

BACKGROUND: Binge-eating disorder (BED) is a relatively new disorder characterized by binge eating without purging. AIM: The purpose of this article is to review the potential use of the recently proposed compounds for the treatment of BED. MATERIALS AND METHODS: A medline of published articles from 1980 to December 2012 was carried out using the following keywords: BED and treatment, topiramate, zonisamide, ghrelin. RESULTS: The pharmacological treatment of BED is still heterogenous and poorly established, mainly for the lack of controlled studies in large samples of patients. CONCLUSIONS: The data on serotonin and norepinephrine reuptake inhibitors and on novel anticonvulsants seem quite promising in terms of efficacy and tolerability. In addition, the preliminary findings on the possibility of modulating appetite through the interference with the ghrelin system suggest new and intriguing ways of intervention in BED.

Subthreshold mood symptoms in patients with fibromyalgia and rheumatoid arthritis.

OBJECTIVES: Although several findings have highlighted the prevalence of Axis I psychiatric disorders in fibromyalgia (FM) and rheumatoid arthritis (RA), very little information is available on the prevalence of subthreshold mood symptoms in these conditions. Therefore, we aimed at comparing the prevalence of subthreshold mood symptoms in rheumatic patients suffering from FM and RA. The hypothesis is that subthreshold mood symptoms are more represented in FM, given the evidence of higher rates of Axis I psychopathology in FM than in RA. METHODS: Sixty patients suffering from FM and 50 from RA, assessed according to the American College of Rheumatology (ACR) criteria, selected in a Rheumatology Department, were included in the study. The subthreshold affective symptoms were assessed by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS: The results showed that FM patients presented significantly higher scores than RA patients in 'mood depressive', 'cognition depressive' domains and in total depressive component. CONCLUSIONS: The present study demonstrates that subthreshold depressive symptoms are more represented in FM than in RA patients. This fact could play a role in the worse quality of life and in the major perception of pain which characterises FM.

Novel treatment options of binge eating disorder.

Obesity is a major problem of modern societies that sometimes, but not necessarily, is associated with binge-eating disorder (BED), a relatively new disorder characterized by binge eating without purging. The purpose of this article is to review the rationale for the potential use of pharmacological treatments in BED, and the potential use of the recently proposed compounds. Therefore, a careful medline of published articles from 1980 to December 2010 was carried out using the following keywords: BED and treatment, topiramate, zonisamide, sibutramine, venlafaxine, duloxetine, ghrelin, opiate blockers. Single case reports, observational studies, opinion articles, and studies concerning adults with syndromes resulting in BED (i.e., night eating syndrome) were also reviewed. All examined papers would indicate that the pharmacological treatment of BED is still heterogenous and poorly established, mainly for the lack of controlled studies in large samples of patients. In any case, the data on serotonin and norepinephrine reuptake inhibitors and on novel anticonvulsants seem quite promising in terms of efficacy and tolerability. In addition, the preliminary findings on the possibility of modulating appetite through the interference with the ghrelin system suggest new and intriguing ways of intervention in BED.

Mitochondrial alterations and neuropsychiatric disorders.

Mitochondria are membrane-enclosed organelle found in most eukaryotic cells, where they generate the majority of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. In addition, they are involved in a range of other processes, such as signalling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. Mitochondria have been implicated in several neuropsychiatric disorders, in particular, depression, anxiety, schizophrenia, autism, and Alzheimer's dementia. Furthermore, the presence of mutations at the level of mitochondrial or nuclear DNA (mtDNA and nDNA, respectively) has been linked to personality disorders, behavioral disturbances, thought alterations, impulsivity, learning impairment, cognitive failures until dementia. The aim of this paper is to review the literature on the relationship between psychiatric symptoms or syndromes and mtDNA mutations or mitochondrial alterations, while highlighting novel therapeutic targets for a broad range of disorders.

Serotonin receptors of type 6 (5-HT6): what can we expect from them?

The serotonin (5-HT) receptors of type 6 (5-HT6) are relatively new. They are quite different from all other 5-HT receptors, as they are characterized by a short third cytoplasmatic loop and a long C-terminal tail, and contain one intron located in the middle of the third cytoplasmatic loop. After some initial controversies, the available findings are now apparently more congruent. Nevertheless, discrepancies still exist, such as those in binding affinity, effects of 5-HT6 ligands on brain catecholamines and behavioral syndromes mediated by them. Much interest in 5-HT6 receptors was triggered by the evidence that some antipsychotics could bind to them. Subsequently, despite the lack of complete information on metabolic patterns of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic and anti-obese drugs. In any case, the available information on both the pharmacology of 5-HT6 receptors is still quite scant. Therefore, with the present paper we aimed at reporting a comprehensive review on the status of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.

Is androstadienone a putative human pheromone?

On the basis of different evidences, androstadienone, a steroid compound produced in the armpit, has been proposed as a human pheromone, although its physiological levels appear too low to induce a response under experimental conditions. For this reason, the majority of researchers in this area puts into question the "legitimacy" of androstadienone, and prefers to consider the axillary extracts in its entirety, like a sort of "medicinal tea", the components of which still remain to be identified, but that taken together may induce a response, or function as a carrier of other active substances. Another option is that androstadienone acts with varying degrees of potency and, at lower concentrations, according to the context and to specific behavioral situations. The aim of this paper is to review all relevant data regarding androstadienone, in order to ascertain whether it may be considered a physiological pheromone and, as such, a possible target of future modulators of some human behaviors.

Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development?

The latest advancement in neurobiological research provided an increasing evidence that inflammatory and neurodegenerative pathways play a relevant role in depression. Preclinical and clinical studies on depression highlighted an increased production of inflammatory markers, such as interleukin (IL)-1, IL-6, tumor necrosis factor-α and interferon- α and γ. On the other hand, acute and chronic administration of cytokines or cytokine inducers were found to trigger depressive symptoms. According to the cytokine hypothesis, depression would be due to a stress-related increased production of pro-inflammatory cytokines that, in turn, would lead to increased oxidative and nitrosative brain damage and to indoleamine 2,3 dioxygenase (IDO) induction, with production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and consequent reduced availability of TRP and serotonin (5-HT). Cytokines would also play a role in the onset of the glucocorticoid resistance, underlying the overdrive of the hypothalamic-pituitary-adrenal axis. Therefore, the activation of the inflammatory and neurodegenerative pathways would lead to the brain damage observed in depression through both reduced neurogenesis and increased neurodegeneration. Besides the 5-HT system, other targets, possibly within the I&ND pathways, should be considered for the future treatment of depression: cytokines and their receptors, intracellular inflammatory mediators, IDO, TRYCATs, glucocorticoid receptors, neurotrophic factors may all represent possible therapeutic targets for novel antidepressants. In addition, it should be also clarified the role of the existing anti-inflammatory drugs in the treatment of depression, and those compounds with the anti-inflammatory and anti-oxidative properties should be examined either as monotherapy or adjunctive therapy. In conclusion, the molecular inflammatory and neurodegenerative pathways might provide new targets for antidepressant development and might be crucial to establish a rational treatment of depression aimed, hopefully, to its causal factors.

Past, present and future drugs for the treatment of obsessive-compulsive disorder.

In the last decades, the treatment of obsessive-compulsive disorder (OCD) has been revolutioned by the introduction into the clinical practice of the selective serotonin (5-HT) reuptake inhibitors (SSRIs), following the observation of the unique response of OCD patients to clomipramine. However, if with no doubt the 5-HT system is central to the pharmacological treatment of OCD, it is unlikely that it represents the whole story. In fact, different studies suggest abnormalities of other neurotransmitters, neuropeptides or second messengers, so that it can be hypothesized that the possible heterogeneity of pathophysiological mechanisms might underlie the different clinical pictures and responses to treatment. Moreover, latest developments in the pharmacology of SSRIs have shown that they share the common property of 5-HT reuptake blockade, but, with the exception of citalopram and escitalopram, they do interact with other receptors and systems. In this paper, the latest findings on pharmacological treatments of OCD will be reviewed, together with a focus on putative targets for future drugs, such as the glutamate system or second messengers, and the problems related to treating OCD in different ages.