Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review.

BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated. OBJECTIVE: The objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity. METHODS: A systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics 'PCR' and 'Schizophrenia', by using MESH terms. RESULTS: An immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation. CONCLUSION: CRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia.

Bupropion Augmentation in a Case of Compulsive Buying Disorder.

BACKGROUND: Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition. CASE: A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion. CONCLUSIONS: Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

A matter of life and death: substance-caused and substance-related fatalities in Ibiza in 2015.

OBJECTIVES AND METHODS: In the framework of the EU-funded project "EU-Madness," we collected and analysed all the reports of fatalities directly or indirectly related to substances of abuse registered in Ibiza from January to September 2015, in order to analyse the characteristics of the sample, the identified substances, and the nature of deaths associated with their consumption. RESULTS: A significant increase of substance-caused deaths with respect to the previous 4 years has been highlighted. Most of the subjects were young males, more than half were not Spanish. Males prevailed also amongst the victims of traffic accidents and suicides. The most commonly involved substances included MDMA, alcohol, cocaine, THC, opiates and prescription drugs. CONCLUSIONS: Although the use of NPS is rapidly increasing in Europe, according to the results from our sample, alcohol and well-known stimulants (MDMA and cocaine) are still the substances of abuse mainly involved in the cases of substance-caused and substance-related fatalities. The significant increase of fatalities in Ibiza in the last 5 years is an issue that must be taken into account and should be better investigated, as other theories besides NPS-increased diffusion should be proposed, and therefore, targeted prevention strategies should be designed.

Substance-related psychopathology and aggressiveness in a nightlife holiday resort: Results from a pilot study in a psychiatric inpatient unit in Ibiza.

OBJECTIVES: We aimed to describe a sample of subjects admitted to a psychiatric unit after the intake of psychoactive substances for recreational purposes. METHODS: Between June and September 2015, 49 subjects were included. Sociodemographic characteristics and psychopathological aspects were investigated, and urine samples for further analysis were collected. Three subgroups (cannabinoids, stimulants, and depressors users) were identified, according to the structured interview regarding substance use and urinalysis. RESULTS: Level of aggressiveness was found to be significantly higher (p < .05) in the cannabinoids subgroup. Self-reported symptom severity was comparable among groups, but trends could be identified: SCL-90 results showed a prevalence of anxiety symptoms among depressors users, hostility or aggression in the tetrahydrocannabinol subgroup, and psychoticism in the stimulants subgroup. CONCLUSIONS: The use of psychoactive substances was be characterised by poly-use of both traditional and novel substances. The presence of aggressiveness emerged as a main feature associated with the use of cannabis and other cannabinoids. Binge drinking and sleep deprivation also represented a relevant component in almost all the evaluated subjects.

Resilience and cross-network connectivity: A neural model for post-trauma survival.

Literature on the neurobiological bases of Post-Traumatic Stress Disorder (PTSD) considers medial Prefrontal cortex (mPFC), a core region of the Default Mode Network (DMN), as a region involved in response regulation to stressors. Disrupted functioning of the DMN has been recognized at the basis of the pathophysiology of a number of mental disorders. Furthermore, in the evaluation of the protective factors to trauma consequence, an important role has been assigned to resilience. Our aim was to investigate the specific relation of resilience and PTSD symptoms severity with resting state brain connectivity in a traumatized population using magnetoencephalography (MEG), a non-invasive imaging technique with high temporal resolution and documented advantages in clinical applications. Nineteen Trauma Exposed non-PTSD (TENP) and 19 PTSD patients participated to a resting state MEG session. MEG functional connectivity of mPFC seed to the whole brain was calculated. Correlation between mPFC functional connectivity and Clinician Administered PTSD Scale (CAPS) or Connor-Davidson Resilience Scale (CD-RISC) total score was also assessed. In the whole group, it has been evidenced that the higher was the resilience, the lower was the cross-network connectivity between DMN and Salience Network (SN) nodes. Contrarily, in the TENP group, the negative correlation between resilience and DMN-SN cross-interaction disappeared, suggesting a protective role of resilience for brain functioning. Regarding our findings as a continuum between healthy and pathological after trauma outcomes, we could suggest a link between resilience and the good dialogue between the networks needed to face a traumatic event and its long-term consequence on individuals' lives.

Alcohol drinking patterns in young people: A survey-based study.

Binge drinking represents a major clinical and public health concern. Here, we investigated the prevalence of binge drinking and its related consequences, in a population of young adults. A questionnaire was administered to a sample of 4275 healthy subjects. In the overall sample, the percentage of binge drinkers was 67.6 per cent; among regular alcohol users, 79.5 per cent reported episodes of binge drinking. Among binge drinkers, several serious consequences were identified (staggering and stuttering, amnesia, loss of control, aggressiveness, sexual disinhibition). Raising awareness about the seriousness of binge drinking may help health care providers to identify cases early on and provide appropriate treatments.

A Case of Resistant Schizophrenia Successfully Treated With Clozapine/Long-acting Injectable Aripiprazole Combination.

BACKGROUND: Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole. CASE: A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events. CONCLUSIONS: Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.

Premenstrual Dysphoric Disorder Without Comorbid Psychiatric Conditions: A Systematic Review of Therapeutic Options.

OBJECTIVES: Premenstrual dysphoric disorder (PMDD) is a disabling condition affecting approximately 2% to 8% of women during reproductive age. It has been recently included in the mood disorder section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, but its treatment as a primary psychiatric illness is still debated, because of the high prevalence of other mental disturbances in PMDD patients. On the other hand, clear clinical guidelines for PMDD patients not suffering from comorbid mental conditions are not yet available. The aim of the present study was therefore to systematically review the original articles pertaining to the treatment of PMDD in adult women free of any current or previous psychiatric comorbidity. METHODS: We searched PubMed to identify published studies on PMDD, including randomized controlled trials, open-label trials, and case series or case reports involving adult women with no history of comorbid mental conditions. The search was conducted in April 2015. RESULTS: We found 55 studies fulfilling our inclusion criteria, 49 of them focused on pharmacological/chemical agents and the remaining 6 on nonpharmacological interventions. CONCLUSIONS: Based on the results of our qualitative synthesis, the best therapeutic option in the treatment of adult PMDD patients free of other mental disorders are selective serotonin reuptake inhibitor antidepressants (especially paroxetine and fluoxetine) and low doses of oral estroprogestins. Other interventions, such as light therapy, cognitive behavioral therapy, food supplements, and herbal medicines, showed promising effects, but other investigations are needed to confirm their efficacy.

Bupropion as an add-on therapy in depressed bipolar disorder type I patients with comorbid cocaine dependence.

OBJECTIVES: The treatment of bipolar disorder type I (BD-I) with a comorbid cocaine dependence disorder (CDD) is a challenge in current psychiatric practice. Drugs with proven efficacy in manic/mixed episodes, such as atypical antipsychotics and mood stabilizers, sometimes do not prevent depressive relapses; on the other hand, the use of antidepressants during acute depressive episodes may increase the risk of a manic switch. The aim of the present study was to investigate the short-term efficacy of bupropion augmentation in acutely depressed BD-I patients with co-occurring CDD. METHODS: Twelve depressed BD-I patients, with a comorbid CDD, treated with valproate 1000 to 1500 mg/d and aripiprazole 10 mg/d, were randomly assigned to receive bupropion 150 mg/d as an open-label add-on therapy (n = 5) or to continue their previous treatment (n = 7). RESULTS: After 4 weeks of observation, patients receiving add-on therapy with bupropion have improved in terms of Hamilton Depression Rating Scale scores and Drug Abuse Screening Test scores, with respect to those of the comparison group, whereas no significant increase of Young Mania Rating Scale scores over time was observed. CONCLUSIONS: Our preliminary findings suggest that combining bupropion with mood stabilizers and atypical antipsychotics may be a good therapeutic option in short-term treatment of depressed BD-I patients with comorbid CDD.

The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.

Pregabalin is an anticonvulsant drug that binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.

The endocannabinoid system: a putative role in neurodegenerative diseases.

BACKGROUND: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. OBJECTIVES: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. MATERIALS AND METHODS: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. RESULTS: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington's, Parkinson's and Alzheimer's diseases. CONCLUSIONS: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.