AIM:Neurological Soft Signs (NSS) represent minor neurological signs related to non-specific cerebral alterations. They have been documented in many psychiatric disorders including schizophrenia (SCZ) and obsessive-compulsive disorder (OCD). Aim of this study was to determine and compare the incidence and severity of NSS in patients with SCZ, in patients with OCD, and healthy control subjects (HCs). METHODS:Using the Neurological Evaluation Scale (NES), this study investigated NSS in 15 SCZ patients, 14 OCD patients, and 15 HCs. PANSS and Y-BOCS were used to evaluate clinical picture in both groups. RESULTS:Patients with SCZ showed significantly higher scores compared to HCs in the NES total and each of the three NES subscales (Integrative Sensory Function, Motor Coordination, and Sequencing of Complex Motor Acts). Patients with OCD also showed significantly higher scores compared to HCs in the NES total, Motor Coordination and Sequencing of Complex Motor Acts, but not in Integrative Sensory Function. No significant differences emerged in the NES total and the various subscales scores between the two patients' groups. CONCLUSIONS:Our results seem to confirm the presence of NSS in both SCZ and OCD. The different types of NSS presented by the two patients' groups versus HCs further supports the findings of widespread cerebral alterations in SCZ, on the other hand, with a preferential involvement of prefrontal and frontal cortex in OCD.

Objective Endocannabinoids have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and might represent potential targets for therapeutic intervention. Objectives of the study were: (1) to measure plasma levels of endocannabinoids in a group of antidepressant-free depressed outpatients; (2) to explore their relationship with the severity of depressive symptoms as subjectively perceived by the patients; and (3) to investigate the effect of the selective serotonin reuptake inhibitor escitalopram on endocannabinoid levels. Methods We measured plasma levels of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anadamide), in 12 drug-free outpatients diagnosed with MDD and in 12 matched healthy controls. In the patient group, endocannabinoids plasma levels were assessed at baseline and after 2 months of treatment with escitalopram. Results Baseline plasma levels of the two endocannabinoids did not differ between depressed patients and healthy controls. However, there was a significant inverse correlation between 2-arachidonoylglycerol levels and the severity of subjectively perceived depressive symptoms. Treatment with escitalopram did not change endocannabinoid levels in depressed patients, although it caused the expected improvement of depressive symptoms. Conclusions Our results suggest that 2-arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms, and raise the interesting possibility that 2-arachidonylglycerol and anandamide are differentially regulated in patients affected by MDD. Also, our data suggest but do not prove that the endocannabinoid system is not regulated by serotonergic transmission, at least in depressed patients.

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.00 and 20.00 hours of the day in healthy men and women, and the neurotrophins concentration was measured in the serum by ELISA. A further aim of the study was to evaluate whether or not the NGF/BDNF variations might be related to specific physiological or psychological traits as mood, feeling good and feeling rested, sexual desire and energy. Heart rate and blood pressure were also monitored at the same hours in each enrolled subject. The anxiety (STAI-T and STAI-S score) and sleeping quality were once evaluated in the morning too. We found that serum BDNF increases in men and decreases in women from morning to evening, while NGF shows a similar ultradian profile between men and women, but with higher concentrations in women. Both neurotrophins also show gender-related associations with psychophysiological variables. High NGF levels correlated with a high score for all the psychological variables in men, but with a low score in women. An inverse correlation was found between BDNF and energy and sexual desire in women, while no correlations were found in men. These data disclose that the condition of well-being (or activity/arousal status) is featured by an increasing NGF profile in men and a negative BDNF/NGF trend in women. The clinical relevance of the present data is discussed.

Background Electroconvulsive Therapy (ECT) has been widely applied to treat schizophrenia (SCZ) in the presence of resistance to pharmacotherapy. The mechanism of action of ECT in schizophrenia has not been fully clarified, though its intrinsic mechanism presents analogies with some neurobiological processes mediated by nerve growth factor (NGF). Objectives The aim of this study was to investigate in patients with treatment-resistant schizophrenia (TRS) the effect of ECT on acute and long-term NGF serum levels and the association with the clinical outcomes. Methods Twelve male inpatients with TRS underwent eight sessions of ECT. Blood samples were collected during the first and the eighth ECT at the following time points: 5 minutes before the induction of seizure and then at 0, 5, 15 and 30 minutes after seizure. Results Following ECT treatment, a substantial clinical improvement in symptom severity was indicated by a significant reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscales scores. Even though the baseline NGF levels showed an increase over time, there were no statistical differences in NGF at time 0 at the first and the eighth ECT session. Furthermore, no correlation was observed between the severity of schizophrenic symptoms and NGF levels. Conclusions This is the first study addressing peripheral NGF during ECT treatment in TRS, as well as the first study in which NGF has been evaluated in different ECT sessions at various time points. These findings may potentiate the knowledge about the neurotrophic effects of ECT and the role of NGF in synaptic plasticity related to possible mechanisms of schizophrenia treatment.

Since 2004, vagus nerve stimulation (VNS) has been used in treatment-resistant or treatment-intolerant depressive episodes. Today, VNS is suggested as possible therapy for a larger spectrum of psychiatric disorders, including schizophrenia, obsessive compulsive disorders, and panic disorders. Despite a large body of literature supports the application of VNS in patients' treatment, the exact mechanism of action of VNS remains not fully understood. In the present study, the major knowledges on the brain areas and neuronal pathways regulating neuroimmune and autonomic response subserving VNS effects are reviewed. Furthermore, the involvement of the neurotrophins (NTs) Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) in vagus nerve (VN) physiology and stimulation is revised. The data on brain NGF/BDNF synthesis and in turn on the activity-dependent plasticity, connectivity rearrangement and neurogenesis, are presented and discussed as potential biomarkers for optimizing stimulatory parameters for VNS. A vagus nerve-neurotrophin interaction model in the brain is finally proposed as a working hypothesis for future studies addressed to understand pathophysiology of psychiatric disturbance.

In the last years, scientific interest has grown towards new types of addiction, especially the Internet Addiction (IA). The IA is characterized by the continuous and compulsive use of the internet, causing significant consequences to everyday life. The IA is not included in the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5). An excessive use of the internet can have major consequences: loss of sleep time, worse working or school outcomes, progressive detachment from real relationships, isolation, loss of interest and irritability. The most widely used instrument to assess IA is the Internet Addiction Test (IAT), introduced by Kimberly Young; however, different factor structures were reported for the instrument. The aim of this study was to analyse the prevalence of IA among 200 Italian university students (F = 100, M = 100; aged 19-40) using the IAT. Our findings indicate that the 9% (18 subjects) has a moderate risk to develop the IA, but no subjects obtained a test score between 80 and 100. The correct use of internet is present in the 23% of the sample (46 subjects), whereas the 68% (136 subjects) spend great amounts of time online. The collected data were analysed using the Italian two-factor structure model, according to Servidio et al. Our results confirm higher levels of problematic internet use in male than in female subjects and among young compared to older people. According to our results, however, the youth age is stronger than male gender in determining the level of problematic internet use. In addition, higher rates of problematic Internet use are present in young girls compared to old girls, while in male subjects the problematic internet use is independent from youth age or adulthood. As far as we are aware no previous studies analysed the relationship between the IAT factors (interpersonal, emotional and obsessive conflict, online time management and compromised personal wellbeing), age and gender.

Graves' disease (GD) is an autoimmune chronic thyroiditis frequently associated with development of Graves' orbitopathy (GO) characterized by proptosis, strabismus, impairment of visual function, ocular surface inflammation and dry eye. As consequence, patients with GO experience impairment of quality of life and social function and could develop a neurobehavioral syndrome, ranging from anxious to depressive or psychotic disorders. To date, the pathogenic mechanism underlying neuropsychiatric disorders in patients with GD has not been clearly understood. In fact, the development of neuropsychiatric disorders in patients with GO has been associated with both the detrimental effects of the altered circulating thyroid hormones on the nervous system, and with the psychological discomfort caused by poor quality of life, reduced social interactions and relapsing course of the disease. This paper summarizes current evidence on neuropsychiatric abnormalities in Graves' disease focusing on its impact on QoL and psychosocial function. We remark the importance of a multidisciplinary approach and we emphasize the potential benefit of neuropsychiatric approach on disease perception, patient compliance to medical and/or surgical treatment and clinical outcomes.

Schizophrenia is a maldevelopmental disease with multifactorial etiopathogenesis linked to disturbances in the prenatal/ perinatal environment and to social factors and/or addictive drugs consumption during adolescence/young adulthood. Adolescence has been demonstrated to represent a very sensitive period for brain development. Exposure to adverse life events (chronic social isolation and/or instability) and/or addictive drugs (opioids, cocaine, cannabinoids, alcohol, nicotine) during adolescence has been linked to deviations in the normal neurodevelopment, producing a brain particularly at risk of mental diseases. Several psychopharmacological drugs and environmental factors have been reported to protect against the detrimental effect on neurogenesis caused by the aforementioned genetic and/or epigenetic vulnerabilities. Nerve growth factor (NGF) is one of the strongest stimuli of adult/adolescent neurogenesis and a promising neuromodulator to prevent and/or ameliorate the various behavioral and cognitive schizophrenic symptoms. Biomed Rev 2017; 28: 62-69. Key words: schizophrenia, neurodevelopment, adolescence, stem cells, adult neurogenesis, addictive drugs, life events, NGF

Several recent research findings indicate that schizophrenia (SCZ) may begin with an abnormal neuro-genesis from embryonic Neural Stem Cells (NSCs) and that this process may be particularly vulnerable to a number of genetic and/or environmental disturbances of early brain development. Since it is now well known that neurogenesis is not confined to the womb, but is a protracted process continuing in postnatal life well into adolescence and beyond, and since in the majority of subjects diagnosed with SCZ the first psychotic break occurs in late adolescence or early adulthood, the aim of our paper is to summarize the main findings supporting a possible link between changes in developmental postnatal neurogenesis and SCZ, with a specific focus on the critical period of adolescence and associated environmental risk factors. Establishing a significant role of adult neurogenesis in the emergence of psychosis will help us not only to better understand the pathogenesis of this neuopsychiatric disorder, but also to provide the key to potential strategies toward possible treatments and/or early corrective interventions.

Introduction: Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD.Methods: A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry "A. Fiorini" Hospital, Terracina (Latina, Italy), was performed.Results: The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium-high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records.Conclusion: Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications.

The present cross-sectional study investigates the relation between Cannabis and the development of a psychotic disorder. The main objective is to explore the relations between Cannabis use and psychosis onset, premorbid adjustment cognitive impairment and familiarity. Forty-three patients with a diagnosis of Psychotic Disorder were recruited and divided in two groups based on Cannabis use before onset: Cannabis-using patients (PCU, N=21) and Cannabis-free patients (PCF, N=22). Cognitive functioning was evaluated by Trail Making Test A and B (TMT), Rey-Osterrieth Complex Figure Test (ROCF), and the Rey Auditory-Verbal Learning Test (RAVLT). Premorbid functioning was assessed retrospectively through the Premorbid Adjustment Scale (PAS). PCU group showed earlier onset of the psychotic disorder compared to PCF (p=0.008). This finding was not influenced by age or positive family history for psychiatric illness. PCU subjects showed a worse premorbid functioning respect to PCF and this difference was found to impact on the early onset in the PCU group. In conclusion the present study suggests the hypothesis of an interactive role of Cannabis and poor premorbid school adjustment in the development of psychotic disorders.

The monovalent cation lithium,whose introduction in psychiatry dates back at the end of the 1940s,remains the first-line agent in the management of patients with bipolar disorder(BD).It is effective in the treatment of moderate-to-severe acute mania,prophylactic for recurrent manic and depressive episodes,and reduces the risk of suicide.It can also boost antidepressants effects

Objective Accumulating evidence is delineating a neuroprotective/neurotrophic role for lithium. However, its primary effects on cognition remain ambiguous. We sought to investigate the profile of cognitive impairment in patients with bipolar disorder and to determine whether continued treatment with lithium preserves cognitive functioning.Methods In this cross-sectional study, we tested 15 euthymic patients with bipolar I disorder undergoing long-term clinical maintenance treatment with lithium (for at least 12 months), 15 matched patients treated with other mood-stabilizing drugs and who had never received lithium, and 15 matched healthy subjects on the Cambridge Neuropsychological Test Automated Battery. Investigated cognitive domains were visual memory, executive functions, attention, decision-making/impulsivity, and response inhibition. We controlled for age, gender, intelligence, and residual psychiatric symptomatology.Results Taken together, bipolar patients demonstrated robust deficits in visual memory and executive functions. Once subdivided in treatment subgroups, only non-lithium bipolar patients demonstrated impairments in visual memory. Attention, decision-making, and response inhibition were preserved in both groups. No correlation emerged between neuropsychological tests performance, clinical, and psychological variables.Conclusions This study is the first to our knowledge to have demonstrated, by means of a highly sensitive test of visual memory, a potential hippocampus neuroprotective effect of lithium in patients with bipolar disorder. Besides, it confirms prior findings of cognitive deficits in euthymic bipolar patients. Copyright (C) 2015 John Wiley & Sons, Ltd.

The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders, with a specific focus on depression, and neurotrophins are reviewed and discussed herein in terms of their circadian significance, and potential translation into clinical practice. Keywords: retinal ganglional cells, mesocorticolimbic circuits, chronotherapy, ocular eye drops administration, neurotrophins

INTRODUCTIONSleep disturbances have long been considered as a cardinal symptom of endogenous depression and dreams in depressed patients usually differ from those of healthy people. The aim of the present study was to investigate dream subjective experiences and their modifications in relation to clinical response in a group of escitalopram-treated depressed patients.METHODSTwenty-seven female patients meeting DSM-IV-TR criteria for Major Depressive Disorder (MDD) and starting SSRI therapy were included in the study. Data about psychopathological status and dreaming subjective experiences were collected at baseline (T0), 4 weeks after the beginning of the treatment (T1) and after further 4 weeks of therapy (T2).RESULTSAt T0 dream experience was impaired and negatively toned. Concomitantly with the decrease of symptoms severity, the 8-week escitalopram treatment yielded to significant improvements in the recall of both quantity and quality of dreams; those patients whit lower clinical benefits kept on reporting impaired dream experiences.DISCUSSIONThe results of the present study evidence how the changes in some specific dreaming characteristics, such as the subjective recall of dream activity, the dream recall quality, the dream emotional content and the dream complexity represent reliable markers of the effectiveness of antidepressant therapy.

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto–striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention, and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto–striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful.

Summarycorpus callosum, which is the largest white matter structure in the brain of all placental mammals, connects the left and right cerebral hemispheres. An alteration in its morphology, hypoconnectivity or hyperconnectivity is a common marker of various neuropsychiatric pathologies. One of these is Aicardi syndrome, which is characterized by a triad of callosal agenesis, infantile spasms and chorioretinal lacunae. Patients affected by Aicardi syndrome frequently display other malformations together with congenital defects of the eyes, ribs and vertebrae. Based on the current clinical knowledge, this syndrome is now recognized as a complex neurodevelopmental disorder that includes neurological and constitutional symptoms. However, literature data have not yet defined the presence of a particular set of symptoms in psychiatric patients with this condition. The present case is the first report in which an on-going compulsive behaviour focused on the insistence to order objects has been observed in Aicardi

Introduction It has recently been highlighted that patients affected by schizophrenia (SCZ) and those affected by bipolar disorder (BD) undergo gradual chronic worsening of cognitive and social functioning. The objective of the current study was to evaluate and compare (using the Facial Action Coding System [FACS]) the way by which patients with the two disorders experience and display emotions in relation to specific emotional stimuli. Materials and methods Forty-five individuals participated in the study: 15 SCZ patients, 15 BD patients, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. Results SCZ and BD patients presented similar incongruent emotive feelings and facial expressions (significantly worse than healthy participants); SCZ patients expressed the emotion of disgust significantly less appropriately than BD patients. Discussion BD and SCZ patients seem to present a similar relevant impairment in both experiencing and displaying emotions; this impairment may be seen as a behavioral indicator of the deficit of social cognition present in both the disorders. As the disgust emotion is mainly elaborated in the insular cortex, the incongruent expression of disgust of SCZ patients can be interpreted as a further evidence of a functional deficit of the insular cortex in this disease. Specific remediation training could be used to improve emotion and social cognition in SCZ and BD patients.