A preliminary study on similarities and dissimilarities of Neurological Soft Signs in schizophrenic and obsessive-compulsive disorders suggests a common maldevelopmental model.

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.

Gender differences in ultradian serum levels of NGF and BDNF correlate with psychophysical traits in healthy humans.

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.

Inverse correlation between plasma 2-arachidonoylglycerol levels and subjective severity of depression.

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.

Vagus nerve stimulation and Neurotrophins: a biological psychiatric perspective.

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.

Quality of life and neuropsychiatric disorders in patients with Graves' Orbitopathy: Current concepts.

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 and neurogenesis: A stem cell approach.

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.

Cannabis use related to early psychotic onset: Role of premorbid function.

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.

Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder.

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.

Potential neuroprotective effect of lithium in bipolar patients evaluated by neuropsychological assessment: preliminary results.

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.

Changes in dream experience in relation with antidepressant escitalopram treatment in depressed female patients: a preliminary study.

INTRODUCTION: Sleep 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. METHODS: Twenty-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). RESULTS: At 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. DISCUSSION: The 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.

Facial expression in patients with bipolar disorder and schizophrenia in response to emotional stimuli: a partially shared cognitive and social deficit of the two disorders.

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.

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: on the scent of the orbitofronto-striatal model.

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.

Comparison of facial expression in patients with obsessive-compulsive disorder and schizophrenia using the Facial Action Coding System: a preliminary study.

BACKGROUND: Research shows that impairment in the expression and recognition of emotion exists in multiple psychiatric disorders. The objective of the current study was to evaluate the way that patients with schizophrenia and those with obsessive-compulsive disorder experience and display emotions in relation to specific emotional stimuli using the Facial Action Coding System (FACS). METHODS: Thirty individuals participated in the study, comprising 10 patients with schizophrenia, 10 with obsessive-compulsive disorder, and 10 healthy controls. All participants underwent clinical sessions to evaluate their symptoms and watched emotion-eliciting video clips while facial activity was videotaped. Congruent/incongruent feeling of emotions and facial expression in reaction to emotions were evaluated. RESULTS: Patients with schizophrenia and obsessive-compulsive disorder presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Correlations between the severity of psychopathological condition (in particular the severity of affective flattening) and impairment in recognition and expression of emotions were found. DISCUSSION: Patients with obsessive-compulsive disorder and schizophrenia seem to present a similarly relevant impairment in both experiencing and displaying of emotions; this impairment may be seen as a chronic consequence of the same neurodevelopmental origin of the two diseases. Mimic expression could be seen as a behavioral indicator of affective flattening. The FACS could be used as an objective way to evaluate clinical evolution in patients.

[Internet addiction disorder and social networks: statistical analysis of correlation and study of the association with social interaction anxiousness]. / Internet addiction disorder e social network: analisi statistica di correlazione e studio dell'associazione con l'ansia da interazione sociale.

INTRODUCTION: Internet Addiction Disorder (IAD) is an emerging psychiatric disorder, assimilable to impulse control problems and related to maladaptive use of new networks and social and virtual technologies. AIM: Our study aims to analyze the presence of IAD among adolescents and to study the correlation with social interaction anxiousness. We investigated also the possibility that the Social Network (SN) represent a source of risk for the development of IAD. MATERIALS AND METHODS: The test group was composed of 250 subjects, aged between 14 and 18 years. They were administered: Young's IAT; IAS (Interaction Anxiousness Scale), AAS (Audience Anxiousness Scale) and SISST (Social Interaction Self-Statement Test) to analyze the dimension of social interaction anxiousness. RESULTS: We found a rate of 2% of the IAD. The SN are the most common use of the Net in our sample, but not the most clicked sites by subjects with IAD. It should be noted, finally, a correlation between social interaction anxiety and IAD, but not a significant difference in scores of social anxiousness scales based on the SN use/non-use. CONCLUSIONS: The use of SN intended as single variable doesn't correlate with increased risk for IAD, or for increased social interaction anxiousness. However, if associated with prolonged use of the net for 5-6 hours or more, or concomitant use of chat rooms and/or net gambling, we find a more significant risk of psychopathology. The data presented require further investigations, in order to guide new pathogenetic models and appropriate intervention strategies.

[Dissociative symptoms in patients with mood and anxiety disorders]. / Presenza di elementi dissociativi in pazienti con disturbi dell'umore e disturbi d'ansia.

AIM: The objective of this study was to evaluate the occurrence of dissociative symptoms in outpatients affected by mood or anxiety disorder and their potential implication in general psychopathology and treatment response. METHODS: The sample was recruited at Italian and Spanish psychiatric outpatient services. The sample consisted in 40 (13 Male, 27 Female) outpatients, 22 Italians (55%) and 18 Spanish (45%). Inclusion criteria were the Axis I diagnosis of any DSM-IV-TR mood or anxiety disorder and Clinical Global Impression/Global Severity Index (CGI) baseline scores > or = 3 and Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) baseline scores > or = 18. General psychopathology, dissociative symptoms and personality traits were respectively assessed by the self-report symptom inventory Symptom Check-List 90 (SCL-90), the Dissociative Experience Scale (DES) and the Cloninger's Temperament and Character Inventory (TCI). RESULTS: Dissociative symptoms emerged as relatively frequent in mood and anxiety disorders. Globally, depression symptoms seem to correlate positively with the dissociative experiences and the severity of global psychopathology. Dissociative symptoms seem to correlate positively with some personality traits and the severity of global psychopathology and should receive further investigation in clinical practice, as might be a predictor of poor response to conventional drug treatment.

Corpus callosum abnormalities and potential age effect in men with schizophrenia: an MRI comparative study.

The goal of this investigation was to evaluate corpus callosum (CC) morphometry in schizophrenia. In consideration of possible confounders such as age, gender and handedness, our study sample was restricted to right-handed male subjects, aged 18-55 years. In addition, we controlled for age at onset, illness duration and exposure to antipsychotic medication. Midsagittal CC linear and area Magnetic Resonance Imaging (MRI) measurements were performed on 50 subjects with schizophrenia and 50 healthy controls. After controlling for midsagittal cortical brain area and age, Analysis of Covariance (ANCOVA) revealed an overall effect of diagnosis on CC splenium width and CC anterior midbody area and a diagnosis by age interaction. Independent Student t tests revealed a smaller CC splenium width in the 36- to 45-year-old age group among the patients with schizophrenia and a smaller CC anterior midbody area in the 18- to 25-year-old age group among the patients with schizophrenia compared with controls. Age, age at onset, illness duration and psychopathology ratings did not show any significant correlations with the whole CC MRI measurements. A negative correlation was found between CC rostrum area and the estimated lifetime neuroleptic consumption. The results are discussed in terms of the possibility that CC structural changes may underlie the functional impairments, frequently reported in schizophrenia, of the associated cortical regions.

Neurological soft signs and cerebral measurements investigated by means of MRI in schizophrenic patients.

Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic prevalence in schizophrenic patients, and correlations between NSS and the most frequently cerebral alterations. The aim of this study was to investigate, by means of MRI, the quantitative alterations of cortical and subcortical structures and their correlation with NSS in a sample of schizophrenic patients. Linear measures of lateral ventricular (Evans ratio), third ventricular (Third Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan and Heinrichs's Neurological Evaluation Scale (NES). Lateral ventricular enlargement showed to be correlated with right stereoagnosia item (p=0.001). Hippocampal atrophy, with right stereoagnosia item (p=0.023), with forefinger-right thumb opposition (p=0.004), forefinger-left thumb opposition (p=0.029 and face-hand extinction (0.26). Third ventricle enlargement showed to be correlated with forefinger-right thumb opposition (p=0.001), forefinger-left thumb opposition(p=0.021) and total sensorial integration (p=0.012). Cerebellar atrophy showed to be correlated with rhythmic drumming item (p=0.042), forefinger-right thumb opposition (p=0.007), forefinger-left thumb opposition (p=0.026), left specular movements (p=0.049), face-hand extinction (p=0.001), right-left confusion (p=0.005) and with left forefinger-nose index (p=0.032). Results obtained confirm the correlation between NSS and neuroanatomical alterations in schizophrenia.

Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness.

Several investigations have suggested pineal gland abnormalities in the pathogenesis of schizophrenia. The pineal volume on brain magnetic resonance imaging scans was calculated in 15 male schizophrenic inpatients and in 16 matched control subjects. The statistical comparison found a significant difference of pineal gland volume between schizophrenics and controls (P = 0.022), with a smaller pineal volume in the schizophrenics. These results do not confirm the previous data of Schizophrenia Res. 14 (1995) 253, showing no significant pineal volumetric differences between schizophrenics and normal controls. Since the present study is based on a smaller but more homogeneous sample of patients, this could reduce the heterogeneity features of the schizophrenic disease. No correlation was found between pineal volume and clinical and psychopathological features of the schizophrenic subjects. Volume reduction in schizophrenia could be at least partially included in the wider brain developmental abnormalities of the illness or in the late effects of previous neuroleptic treatments.