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Background: The gastrointestinal system hosts roughly 1,800 distinct phyla and about 40,000 bacterial classes, which are known as microbiota, and which are able to influence the brain. For instance, microbiota can also influence the immune response through the activation of the immune system or through the release of mediators that are able to cross the brain blood barrier or that can interact with other substances that have free access to the brain, such as tryptophan and kynurenic acid, which is a metabolite of tryptophan and which has been involved in the pathogenesis of schizophrenia. Objectives: This paper reviews the possible relationships between microbiome, schizophrenia and treatment resistance. Given the possibility of a role of immune activation and alterations, we also describe the relationship between schizophrenia and immune inflammatory response. Finally, we report on the studies about the use of probiotic and prebiotics in schizophrenia. Methods: Cochrane library and PubMed were searched from the year 2000 to 2018 for publications about microbiome, immune-mediated pathology, schizophrenia and neurodevelopmental disorders. The following search string was used: (microbiome or immune mediated) AND (schizophrenia OR neurodevelopmental disorder). Associated publications were hand-searched from the list of references of the identified papers. A narrative review was also conducted about the use of probiotics and prebiotics in schizophrenia. Results: There exists a close relationship between the central nervous system and the gastrointestinal tract, which makes it likely that there is a relationship between schizophrenia, including its resistant forms, and microbiota. This paper provides a summary of the most important studies that we identified on the topic. Conclusions: Schizophrenia in particular, remain a challenge for researchers and practitioners and the possibility of a role of the microbiome and of immune-mediated pathology should be better explored, not only in animal models but also in clinical trials of agents that are able to alter gut microbiota and possibly influence the mechanisms of gastrointestinal inflammation. Microbiome targeted treatments have not been well-studied yet in patients with mental illness in general, and with schizophrenia in particular. Nonetheless, the field is well worth of being appropriately investigated.

Background: Intermittent explosive disease (IED) is a psychiatric disorder characterized by intermittent attacks of rage and violence frequently resistant to pharmacological therapy. Deep brain stimulation (DBS) of the posteromedial hypothalamus has been applied with fair results and clinical improvement with some surgical morbidity due to neurovegetative side effects. The anterior limb of the internal capsule/ventral capsule/ventral striatum (VC/VS) has never been used alone as a target for this disease. Objectives: The aim of this study is to evaluate the efficacy of bilateral DBS of the VC/VS for the treatment of IED. Methods: We performed bilateral DBS of the VC/VS in a 21-year-old patient with IED. This young man had a traumatic birth complicated by hypoxia, and he showed a mild mental impairment. Different pharmacological treatments were carried out with no results before DBS was proposed to the patient's relatives after multidisciplinary approval. Results: After 22 months of high-frequency monopolar bilateral DBS of the VC/VS, the patient showed a significant improvement. Postoperative 18F-FDG PET-CT studies ruled out a reduction of the hypermetabolic areas located in the limbic system previously detected in pre-operative investigations. Conclusions: Bilateral DBS of the VC/VS may be considered for the treatment of IED without the risk of neurovegetative side effects.

A number of MRI studies have shown focal or diffuse cortical gray matter (GM) abnormalities in patients with post-traumatic stress disorder (PTSD). However, the results of these studies are unclear regarding the cortical regions involved in this condition, perhaps due to the heterogeneity of the PTSD population included or to the differences in the methodology used for the quantification of the brain structures. In this study, we assessed differences in cortical GM volumes between a selected group of 25 drug-naive PTSD patients with history of adulthood trauma and 25 matched non-traumatized controls. Analyses were performed by using two different automated methods: the structural image evaluation using normalization of atrophy (SIENAX) and the voxel-based morphometry (VBM), as we trusted that if these complementary techniques provided similar results, it would increase the confidence in the validity of the assessment. Results of SIENAX and VBM analyses similarly showed that cortical GM volume decreases in PTSD patients when compared to healthy controls, particularly in the frontal and occipital lobes. These decreases seem to correlate with clinical measures. Our findings suggest that in drug-naïve PTSD patients with a history of adulthood trauma, brain structural damage is diffuse, with a particular prevalence for the frontal and occipital lobes, and is clinically relevant.

Nell'ultimo decennio la qualita della vita ha acquisito una sempre maggiore rilevanza come misura di esito sociale e clinico (Katschnig, 1997) dei disturbi mentali. Vi e un ampio consenso sul fatto che il costrutto della qualita della vita è multidimensionale e comprende la percezione che il paziente ha delle relazioni sociali, della propria salute fisica, della capacità di svolgere le attivita quotidiane domestiche e lavorative e del proprio benessere in generale (Patrick & Erickson, 1988). Mentre le misure di funzionamento si propongono di quantificare la compromissione in modo oggettivo, le misure della qualita della vita valutano la capacita del soggetto di trarre soddisfazione e piacere da varie attivita e richiedono una valutazione soggettiva. La definizione di qualita della vita del Quality of Life Group dell'Organizzazione

The Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is increasingly used in psychiatry because it gives emphasis to the subjective perspective of patients on physical, psychological and social domains. This paper reports on the validation of the Italian version of the Q-LES-Q in a large multicenter study (EQUIP) conducted at five Italian sites on outpatients in treatment for anxiety disorders. Study participants underwent a broad assessment of psychopathology including the MINI-International Neuropsychiatric Interview, the Symptom Checklist (SCL-90) and the Clinical Global Impression (CGI). Cronbach’s alpha was used to determine the internal consistency of the Q-LES-Q areas and Pearson’s r was used to analyze the correlation between the areas of Q-LES-Q and those of the other instruments. The internal consistency of the Q-LES-Q proved to be substantial (>0.80 in each of the areas) as well as the test–retest reliability. The convergent validity of the Q-LES-Q vs. the Work and Social Adjustment Scale was examined. High correlations were found between scales measuring similar constructs in the two instruments and lower correlation between scales measuring different constructs. In conclusion, the Italian version of the Q-LES-Q proved to be as valid and reliable as the original English version.

In normal subjects, the secretion of melatonin, the pineal hormone that regulates the rhythm of many functions, exhibits a circadian pattern synchronized with the day-night cycle. An alteration of this secretory pattern has been found in various psychiatric disorders (seasonal affective disorder, bipolar disorder, unipolar depression, bulimia, anorexia, schizophrenia, panic disorder, obsessive compulsive disorder). At present, it is not known if such alterations have an etiological role or are secondary to the dysfunctions underlying the different disorders. In addition, we do not know if the involvement of melatonin in several disorders has the same significance in the pathophysiology of each disorder. An understanding of the role of the pineal hormone and of its alterations in psychiatric diseases could help to identify the biological mechanisms underlying such disorders.

Psychiatrists have always maintained that there is a relationship between aggressive behaviour and suicide in depressed patients. However, this relationship is based on inconsistent and undocumented hypotheses, not on reliable clinical experimental data. The present study was designed to investigate the relationship between aggressive behaviour assessed by means of the Buss and Durkee Hostility Inventory (BDHI), and suicide in a sample of 134 depressed out-patients. The group with a higher level of suicidal behaviour was of younger age. The association between depressive subtypes (major depression, recurrent; major depression, single episode; bipolar disorder, depressive episode; dysthymia) and suicidality was found to be statistically significant. In contrast, there was no correlation between depressive subtypes and aggressive behaviour. The relationship between suicide and guilt as measured by the BDHI suggests that, in depression, suicidal behaviour becomes part of a symptom pattern in which aggression does not appear to be the main component. The suicide dimension arises when the cognitive sphere is involved. In fact, in depression, suicide is included among the cognitive disturbances, together with guilt, paranoid and obsessive-compulsive symptoms, depersonalization/derealization and agitation.

Numerous studies suggest that seasonal birth may play a pathogenic role in the development of mental disorders. A birth excess of 10% during winter and spring has been shown in schizophrenia. The few studies carried out on affective disorders revealed a significant increase of births in the first quarter of the year in bipolar disorders and major depressive disorder. Subjects with seasonal affective disorder show a peak of births in May. Data on personality, eating and ‘neurotic’ disorders are less consistent. At the moment there are no data in the literature about anxiety disorders.

Most brain imaging studies have showed smaller hippocampal volume in adults with chronic PTSD; however, some other studies have not replicated this finding. Most of these investigations included subjects with other psychiatric comorbidities, such as major depression or alcohol abuse. The prevalence of psychiatric comorbidities in PTSD is generally high and this makes it difficult, if not impossible, to disentangle the contribution of other disorders to hippocampal volume. Therefore, the main goal of the current study is to compare hippocampal volumes of healthy subjects and drug-naive patients with PTSD caused by different types of mixed civilian traumas (i.e. car accident, physical abuse, sudden death of a family member, assault or robbery, natural disaster and traumatic abortion) and without comorbidity conditions. Magnetic resonance imaging (MRI) was used to measure the hippocampi, total cerebrum, gray matter, white matter and cerebrospinal fluid volumes in 34 patients with single diagnosis of PTSD, and 34 case-matched non-PTSD comparison subjects. The patients with single diagnosis of PTSD had an 11.8% smaller left hippocampus (p

Background Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. Methods Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. Results Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS. Limitations Limitations of this study are the open design and the small sample size. Conclusions Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

Abnormal light-related behaviors have been described for patients with panic disorder (PD). The present study was undertaken to investigate the retinal light response in PD using electroretinography (ERG). The authors conducted bwave ERG measurements with a bright light (after dark adaptation) in 28 patients with PD and 28 control subjects. There were no significant differences in the mean b-wave amplitude between the two groups, but the retinal response to light in PD patients was generally lower than in healthy subjects. A large interindividual variability was found; also noted was a significant difference in the mean b-wave amplitude between the right and left eyes in the control group. The data indicate subtle variation of retinal photosensitivity in a subgroup of patients with PD. Because dopaminergic retinal activity affects b-ERG amplitude, the authors hypothesize that the dopaminergic system is involved in the response to light in PD patients.

A dysfunctional relationship between parents and children can influence cognitive and emotional development and contribute to the development of psychiatric disorders, particularly panic disorder (PD). With the aim of exploring childhood experiences of parenting in PD patients, we compared subjectively perceived climate and objective recall by administering the Parental Bonding Instrument and 10 adjunctive items to 22 out-patients and 22 matched controls. Our analysis showed that DSM-III-R-diagnosed PD patients reported their parents to be significantly less caring than did the control group, while there was no significant difference in objective recall of parenting experiences.

Several studies have investigated the seasonal distribution of the birth dates of patients with psychiatric diseases. Our purpose was to verify if there is a specific distribution (by month) of birth dates in subjects with panic disorder (PD). The birth dates of 843 outpatients with a diagnosis of PD were compared with those of 1,181 subjects with other mental diseases. The birth dates of psychiatric patients were compared to those of the general Tuscane and Italian populations. The monthly distribution of birth in patients with PD (with and without comorbidity) peaked in September to December, while no relevant deviation in birth rate was observed in other mental diseases. Our results suggest a pathogenic role of birth seasonality in the development of PD.

In order to verify if task-dependent EEG asymmetry is related to emotivity or personality traits, the relationship between EEGraphic (EEG mapping) asymmetry, personality aspects, and emotional-affective state in 12 healthy volunteers was evaluated by means of standardized methods (SAD and CPI). Our subjects show an EEG asymmetry which is currently attributed in the literature to anxiety. In our subject the absence of anxiety and the presence of hyperthymic characteristics suggests that the different individual trends observed in various studies which have used methods similar to ours, could, at least partly, depend on interference on these variables.

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.