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Objective The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive–compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. Design The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. Results Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors. Conclusions Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive–compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact. Copyright © 2015 John Wiley & Sons, Ltd.

Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity.We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF).At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P0.001 and P0.02, respectively).High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated.

Objectives. To review the role of Wnt pathways in the neurodevelopment of schizophrenia. Methods: Systematic PubMed search, using as keywords all the terms related to the Wnt pathways and crossing them with each of the following areas: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action. Results: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established. Conclusions: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Background Dickkopf-1 (DKK1) is an inhibitor of the canonical Wnt pathway, which is known to be impaired in both psychotic and neurodegenerative disorders. Here, we examined serum DKK1 levels as an indicator of ongoing neurodegeneration in psychotic patients, with or without a recent or current history of drug abuse. Methods We measured serum DKK1 levels by ELISA in 22 inpatients with psychosis and no history of drug abuse, 22 with psychosis and drug abuse, and 16 controls. We rated psychopathology using the following rating scales: the Positive and Negative Syndrome Scale (PANSS); the Clinical Global Impressions (CGI) severity scale; and the Global Assessment of Functioning (GAF) scale. Extrapyramidal motor symptoms were assessed by the Simpson-Angus Neurological Rating Scale (NRS). Results Inpatients with psychosis and comorbid substance abuse showed significantly higher serum DKK1 levels than inpatients with psychosis and no comorbid substance abuse or controls. Comorbid patients had earlier onset, longer duration of psychosis, and more severe extrapyramidal motor symptoms. However, we did not find any significant correlation between DKK1 levels and rating scale scores. Conclusion Psychosis led to elevated serum DKK1 levels, and substance abuse led to a further increase. Knowing that there is a correlation between brain and blood levels of DKK1, we speculate that the observed increase in DKK1 levels reflects drug-induced neurotoxicity in our patients.

Background: Intimate partner violence (IPV) is the most frequent type of violence against women. We compared clinical and radiological IPV characteristics to stranger assault (SA). Methods: We retrospectively identified 123 women with IPV from court reports and matched them to 124 SA. Clinical and radiological characteristics were evaluated by testing their sensitivity, specificity, positive and negative predictive value for IPV, and the strength of their association with IPV. Results: IPV women referred with more delay to the emergency department (ED), had more ED accesses, and showed more mismatch between reports to the triage and disclosures to the ED physician. They also displayed more head, neck, and face injuries, and new-plus-old fractures. Conclusion: The identification of specific features may help ED physicians to suspect IPV.

Background and Aim: Obsessive-compulsive disorder (OCD) is a severe, highly prevalent and chronically disabling psychiatric disorder that usually emerges during childhood or adolescence. This paper aims to review the literature on functional neuroimaging in OCD, analysing the reported dysfunctional connectivity in the corticostriatothalamocortical circuitry. Method: This study included papers published in peer-reviewed journals dealing with functional imaging in OCD. Results: Striatal dysfunction, mainly of the caudate nucleus, leads to inefficient thalamic gating, resulting in hyperactivity within the orbitofrontal cortex (intrusive thoughts) and the anterior cingulate cortex (non-specific anxiety). Compulsions consist of ritualistic behaviours performed to recruit the inefficient striatum and neutralise unwanted thoughts and anxiety. Functional neuroimaging findings are discussed against the background of specific cognitive impairments, mainly regarding visuospatial processing, executive functioning and motor speed. Cognitive deficits are partial and specific, matching imaging data. Conclusions: Several studies have targeted brain regions hypothesised to be involved in the pathogenesis of OCD, showing the existence of dysfunctional connectivity in the corticostriatothalamocortical circuitry. Improvements in spatial resolution of neuroimaging techniques may contribute to a better understanding of the neurocircuitry of OCD and other anxiety disorders.

Toscana virus (TOSV) infection may often cause symptomatic meningitides and encephalitides. These usually subside in few days and their sequelae do not last for more than few weeks. We here report the case of a 49-year-old man who developed encephalitis after being bitten by phlebotomi in a region near southern Tuscany, where TOSV is endemic, and who developed postencephalitic seizures and subsequently, persistent personality alterations, characterized by sexually dissolute behavior and aggressiveness. One year after infection, the patient needs a combination of an SSRI antidepressant and a mood stabilizer/anticonvulsant to obtain less than optimal symptom improvement. This points to the need of establishing better preventive measures in Tuscany and nearby regions.

Introduction: Deep transcranial magnetic stimulation (dTMS) is a new form of TMS allowing safe stimulation of deep brain regions. The objective of this preliminary study was to assess the role of dTMS maintenance sessions in protecting patients with bipolar disorder (BD) or recurrent major depressive disorder (MDD) from developing depressive or manic relapses in a 12-month follow-up period. Methods: Twenty-four drug-resistant patients with a current depressive episode and a diagnosis of MDD or BD have been enrolled in the study. All the participants underwent daily dTMS sessions for 4 weeks. One group (maintenance – M group) received additional maintenance dTMS sessions weekly or twice a week. Results: After the first dTMS cycle, a significant reduction of Hamilton Depression Rating Scale (HDRS) scores was observed in all participants. Subsequently, the HDRS mean scores did not significantly change over time in the M group, while it significantly increased in the non-M-group after 6 and 12 months. Discussion: This study confirms previous evidence of a positive therapeutic effect of dTMS on depressive symptoms and suggests that, after recovery from acute episodes, maintenance dTMS sessions may be helpful in maintaining euthymia in a 12-month follow-up period.

A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome.

Background Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. Case report A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. Conclusions dTMS may be an alternative antidepressant strategy in patients with MMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation.

Electroconvulsive therapy (ECT) is effective in treatment-resistant depression (TRD). It may act through intracellular process modulation, but its exact mechanism is still unknown. Animal research supports a neurotrophic effect for ECT. We aimed to investigate the association between changes in serum brain-derived neurotrophic factor (sBDNF) levels and clinical improvement following ECT in patients with TRD. Twenty-one patients with TRD (2 men, 19 women; mean age, 63.5 years; S.D., 11.9) were assessed through the Hamilton Depression Rating Scale (HDRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale, Severity (CGIs) before and after a complete ECT cycle. At the same time-points, patients underwent blood withdrawal for measuring sBDNF levels. ECT significantly reduced HDRS, BPRS, and CGIS scores, but not sBDNF levels. No significant correlation was found between sBDNF changes, and each of HDRS, BPRS, and CGIs score changes. sBDNF levels in TRD patients were low both at baseline and post-ECT. Our results do not support that improvements in TRD following ECT are mediated through increases in sBDNF levels.

The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.

Introduction: Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. Methods: Twelve MDD patients and 11 with concomitant MDD and AUD (MDDþAUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDDþAUD, and functioning with the Global Assessment of Functioning (GAF). Results: There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDDþAUD, and 55.2% and 67.1% for MDD (po0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD þ AUD than in MDD Limitations: The small sample size and factors inherent to site and background treatment may have affected results. Conclusions: High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation.

Several questions arise from the recent use of behavioral genetic research data in the courtroom. Ethical issues concerning the influence of biological factors on human free will, must be considered when specific gene patterns are advocated to constrain court's judgment, especially regarding violent crimes. Aggression genetics studies are both difficult to interpret and inconsistent, hence, in the absence of a psychiatric diagnosis, genetic data are currently difficult to prioritize in the courtroom. The judge's probabilistic considerations in formulating a sentence must take into account causality, and the latter cannot be currently ensured by genetic data.

Background: Craving for alcohol is associated with abnormal activation in the dorsolateral prefrontal cortex. Deep transcranial magnetic stimulation (dTMS) has shown promise in the treatment of depression. There are few treatment options for treatment-resistant dysthymic disorder comorbid with alcohol use disorder. Objective: To investigate the possible anticraving efficacy of bilateral dorsolateral prefrontal cortex high-frequency dTMS in 3 patients with comorbid long-term DSM-IV-TR dysthymic disorder and alcohol use disorder. Method: Three patients with alcohol use disorder with dysthymic disorder in their detoxification phase (abstaining for > 1 month) underwent twenty 20-minute sessions of 20 Hz dTMS over the dorsolateral prefrontal cortex over 28 days between 2011 and 2012. Alcohol craving was rated with the Obsessive Compulsive Drinking Scale and depressive symptoms with the Hamilton Depression Rating Scale. Results: All 3 patients responded unsatisfactorily to initial intravenous antidepressant and antianxiety combinations but responded after 10 dTMS sessions, improving on both anxiety-depressive symptoms and craving. This improvement enabled us to reduce antidepressant dosages after dTMS cycle completion. Discussion: High-frequency bilateral dorsolateral prefrontal cortex dTMS with left prevalence was found to produce significant anticraving effects in alcohol use disorder comorbid with dysthymic disorder. The potential of dTMS for reducing craving in patients with substance use disorder deserves to be further investigated.

A 24-year-old man experiencing comorbid body dysmor- phic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms im- proved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may im- prove symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery.Case description. A 51 years-old man had a history of putative petit mal seizures since adolescence and left frontotemporal lobectomy after a major traffic accident at age 17. He subsequently developed quickly generalizing partial complex seizures, associated with severe behavioural alterations and personality changes; the condition was left untreated. A further seizure-related loss of consciousness led to another traffic accident at age 47.The patient was administered 200 mg/day topiramate, 600 mg/day quetiapine, 1000 mg/day valproate, 1200 mg/day gabapentin and 800 mg/day carbamazepine.The instituted anti-epileptic treatment reduced seizure frequency and severity, but did not affect psychiatric symptomatology, which even worsened. An association between anti-epileptic drugs with mood stabilizing properties and an atypical anti-psychotic dramatically improved psychiatric symptoms, but did not prevent the patient from needing long-term healthcare.Long-term untreated epilepsy may expose to accident proneness and further psychiatric deterioration. Early diagnosis and treatment of epilepsy may help in avoiding a potentially lethal vicious circle.

A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.

Recent functional neuroimaging studies show that the amygdala has a central role in threat evaluation, in response to conditioned and unconditioned stimuli, in fear learning and fear extinction. The amygdala is involved in the pathophysiology of phobias and anxiety. In this review we critically examine the main findings of functional neuroimaging studies reporting data on the amygdala. Findings suggest that the response of the amygdala to threatening stimuli is mainly modulated by the infralimbic and prefrontal cortices, which inhibit activation of the amygdala (top-down inhibition), and by the hippocampus, the function of which is related to stimulus learning. The activity of the amygdala is modulated by various factors, like stimulus type and origin, emotion triggered by stimulus perception, and attention. The neural network comprising the amygdala and the frontal cortex is involved not only in top-down inhibition, but also in the emotional perception of facial expressions. This network also includes the thalamic pulvinar, which is densely interconnected with the amygdala, directly or indirectly, and which is activated by emotional face recognition of scary fear. Both top-down inhibition mechanisms and emotional face recognition are altered in anxiety disorders, particularly in specific and social phobia, resulting in reduced amygdalar activity inhibition after anxiety - or fear - inducing stimulus perception. Future functional neuroimaging studies will be able to provide new insights of normal and altered neurophysiology of the amygdala.

OBJECTIVES To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode. METHODS Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission. RESULTS The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse. CONCLUSIONS Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

Background: The ability to facial emotion recognition (FER), a key component of socioemotional competence, is often impaired in schizophrenic disorders. The purpose of the present study was to examine the relationship between emotion recognition performance and symptoms in a group of patients with schizophrenia spectrum disorders. Sampling and Methods: Seventy-nine patients meeting DSM-IV-TR criteria for schizophrenia, schizophreniform disorder and schizoaffective disorder were assessed by the Positive and Negative Syndrome Scale and a FER task. In schizophrenia patients and healthy control subjects, FER performance was compared. In order to avoid a possible confounding role of cognitive impairment, we carried out partial correlations corrected for an index of global cognition. Results: Patients performed worse than a healthy control group on all negative emotions. Partial correlations showed that cognitive/disorganized symptoms correlated with a worse performance in the FER task, whereas no correlations were found with positive, negative, excitement and depressive symptoms. Conclusions: Our findings support that in schizophrenia FER impairment is specific for negative emotions and that there is a relationship between this deficit and cognitive/disorganized symptoms, regardless of the general cognitive level.

Objective An 18-year-old man with Arnold–Chiari malformation (ACM) type I developed sudden panic attacks. He also manifested sleep disorder, cannabis abuse, and psychosis-risk syndrome (PRS). Although with average–superior intelligence, he had executive dysfunction. This prompted us to explore the relation between ACM, cannabis abuse, PRS and panic disorder. Method We report the case and briefly review the literature focusing on ACM and psychiatric disorders. Results Behavior therapy led to gradual abstinence from cannabis with disappearance of anxiety symptoms. The patient is currently well and maintained on omega-3 polyunsaturated fatty acids. Conclusions Locus coeruleus compression and cannabis abuse may have triggered the symptoms, and the latter might also be PRS-related. PRS and anxiety symptoms should be explored in ACM patients to allow better prevention of psychosis and anxiety disorders.

A 36-year-old man with comorbid panic disorder with agoraphobia, major depression, and histrionic personality disorder since age 21 was resistant to combined drug and psychotherapy treatment. His conditions had progressively worsened with time, causing him to withdraw socially and to simultaneously require continuous physical restraint, which further worsened his functioning. He spent almost 3 consecutive years in restraint, until he consented to receive bilateral ECT treatment. He improved after 13 sessions in all areas (social and role functioning, and panic, depressive, and histrionic symptoms) and is well 3 months later with a lithium-atypical antipsychotic combination.

Functional neuroimaging studies show that hypnosis affects attention by modulating anterior cingulate cortex activation and uncoupling conflict monitoring and cognitive control function. Considering functional changes in the activation of the occipital and temporal cortices, precuneus, and other extrastriate visual areas, which account for hypnosis-induced altered reality perception, the role of mental imagery areas appears to be central under hypnosis. This is further stressed by the fact that motor commands are processed differently in the normal conscious state, deviating toward the precuneus and extrastriate visual areas. Functional neuroimaging also shows that posthypnotic suggestions alter cognitive processes. Further research should investigate the effects of hypnosis on other executive functions and personality measures.

The elderly population is more frequently subjected to depressive mood compared to the general population and show peculiarities affecting responsiveness; furthermore, aged people need also special care. Duloxetine is a relatively new antidepressant that proved to be effective in adult depression, but has received little attention in elderly population heretofore.To review the evidence of duloxetine in late-life major depressive disorder (MDD).A systematic review of studies focusing on the use of duloxetine in MDD in the elderly has been carried out through the principal specialized databases, including PubMed, PsycLIT, and Embase.Only a handful of papers were specifically dedicated to this issue. Duloxetine was found to be effective and safe in old-age MDD, to be better than placebo on many clinical measures in all studies, and to better differentiate from placebo with respect to selective serotonin reuptake inhibitors. Compared to placebo, its side-effect profile is slightly unfavorable and its drop-out rate is slightly higher. Furthermore, when pain is present in old-age MDD, duloxetine is able to reduce it.The efficacy and safety of duloxetine in old-age depression are similar to those encountered in adult MDD. There is a relative lack of comparative studies other than with placebo. The special needs of elderly patients with MDD must be addressed with close patient contact to avoid the perils of inappropriate dosing.

Objectives: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders. Methods: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion. Results: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders. Conclusions: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.

Specific phobias (SPs) are common, with lifetime prevalence estimates of 10%. Our current understanding of their pathophysiology owes much to neuroimaging studies, which enabled us to construct increasingly efficient models of the underlying neurocircuitry. We provide an updated, comprehensive review and analyze the relevant literature of functional neuroimaging studies in specific phobias. Findings are presented according to the functional neuroanatomy of patients with SPs. We performed a careful search of the major medical and psychological databases by crossing SP with each neuroimaging technique. Functional neuroimaging, mostly using symptom provocation paradigms, showed abnormal activations in brain areas involved in emotional perception and early amplification, mainly the amygdala, anterior cingulate cortex, thalamus, and insula. The insula, thalamus and other limbic/paralimbic structures are particularly involved in SPs with prominent autonomic arousal. Emotional modulation is also impaired after exposure to phobic stimuli, with abnormal activations reported for the prefrontal, orbitofrontal and visual cortices. Other cortices and the cerebellum also appear to be involved in the pathophysiology of this disorder. Functional neuroimaging identified neural substrates that differentiate SPs from other anxiety disorders and separate SP subtypes from one another; the results support current Diagnostic and Statistical Manual of Mental Disorders, 4th edition-Text Revision (DSM-IV-TR) diagnostic subtyping of SPs. Functional neuroimaging shows promise as a means of identifying treatment-response predictors. Improvement in these techniques may help in clarifying the neurocircuitry underlying SP, for both research and clinical-therapeutic purposes.

We describe a case of factitious disorder with physical and psychological symptoms comorbid with bipolar I disorder in a 37-year-old woman. Since the onset of bipolar disorder, which occurred at the age of 31, she increasingly complained of physical symptoms, compulsively seeking medical and surgical interventions. She has been hospitalised several times and her Munchausen-type factitious disorder recently appeared to be developing into Munchausen by proxy, involving her 11-year-old daughter. The patient adhered poorly to stabilising and antipsychotic drug treatment and did not improve through the years. We here analyse her mood phases, which were always associated with changes in the quality of factitious symptoms, according to whether the disorder was in its depressive phase (somatic complaints and suicidal ideation prevail), or in its manic or mixed phase (medical intervention-seeking and manipulation of clinicians to obtain surgical interventions). We also briefly discuss some important forensic issues to consider in similar cases, mainly stemming from the psychotic aspects of these two co-occurring disorders. Clinicians should be aware of some patients’ ability to produce signs and symptoms of physical and/or psychological illness and consult psychiatrists before giving consent to invasive diagnostic procedures or surgery.

A woman with bipolar disorder I, histrionic personality disorder, and suicidal ideation with repeated suicide attempts, who had been treated for 2 years with mood stabilizers, antipsychotics, and benzodiazepines, received a total of 8 bitemporal-biparietal electroconvulsive therapy sessions. Her suicidal ideation and self-harm behavior disappeared immediately after the first session and her psychopathology soon after. This supports the existence of a relatively independent suicidal syndrome and confirms data on its immediate responsiveness to electroconvulsive therapy. Electroconvulsive therapy must not be long withheld from patients with such characteristics to reduce unnecessary sufferance and suicidality.

Objective A patient presenting with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar disorder was found to be affected by high iron hemochromatosis. This prompted us to explore the relation between bipolar disorder and iron overload. Method We report the case and review the peer-reviewed literature focusing on mood symptoms in patients with hemochromatosis or iron overload. Animal studies of brain effects of iron overload are summarized. High iron hemochromatosis was confirmed by genetic testing, and treatment was instituted to address iron overload. Results Patient's bipolar symptoms completely subsided after phlebotomic reduction of iron overload. Conclusion Clinicians should explore the possibility of iron overload and seek genetic confirmation of hemochromatosis in resistant bipolar disorder to avoid unnecessary medication.

The perception of fear and subsequent appropriate behavioral responding are crucial for the adaptation of species to their living environment. Functional neuroimaging studies of the neural basis of fear during the last few decades in humans contributed to significant advancement in the understanding of its mechanisms. Imaging studies help us delineating the role of amygdala-based neurocircuitry in fear activation and attention capture. The aim of this paper was to briefly review the most recent functional neuroimaging studies of fear perception, modulation and learning. Important knowledge was acquired about the factors that set fear in motion, including the role of nonconscious processes and the character of fear in guiding attention. A subcortical network interacts with the prefrontal cortex to modulate emotional response that allows better coping with environmental and social circumstances. Fear learning reduces the need to relearn about danger, and flexibility processes readjust fear behavior when external circumstances change. Future improvement of functional and other neuroimaging techniques may promote better clarification of the neurocircuitry involved in fear perception, learning and modulation.