Behavioral dysregulations by chronic alcohol abuse. Motivational enhancement therapy and cognitive behavioral therapy outcomes.

Patients with alcohol use disorder (AUD) do not manifest homogeneous clinical symptoms. Various studies described both cognitive impairments and psychiatric disorders among people with AUD. This disorder is one of the most frequent mental disorders in developed countries, due to excessive alcohol consumption. Alcohol is toxic as it increases the production of reactive oxygen species (ROS) and can cause dependence. This causes negative effects on brain development and cognitive functions that affect the individual's work, health, and social life. Current pharmacology treatment for alcohol addiction is based on direct action against the neurotransmitters involved in alcohol dependence. AUD patients without comorbid psychiatric disorders or severe cognitive deficits are defined as "pure alcoholics". To date, poor is known about effective treatments for this typology of AUD patients. Psychotherapy is largely used in resolving many psychiatric disorders, including substance use disorders. Motivational enhancement therapy (MET) and cognitive-behavioral therapy (CBT) are two psychotherapies used to achieve and maintain abstinence in patients affected by substance use disorders. This short review aims to describe two CBT and MET and to present the advantages and disadvantages of these two psychotherapies in the treatment of AUD.

Cancer screenings among sexual and gender minorities by midwives' point of view.

INTRODUCTION: Although women belonging to sexual and gender minorities are more at risk of gynecological and breast cancer, pieces of evidence have been provided that this population finds hardships getting involved in cancer screening programs. This happens because they tend to avoid clinical settings because of fear of discrimination, heteronormative assumptions, heterosexism, classism, and homophobic slurs by healthcare professionals. On the other hand, medical programs that allow healthcare providers to have experience with LGBTQ people are scarce and there are no specific tools to assess sexual cancer risks in this population. EVIDENCE ACQUISITION: Studies included were obtained searching MEDLINE with keywords "lesbians," "queer women," "trans women," "LGBTQ women," "cervical cancer screening," "pap test," "oncology screening," "mammogram" and "prevention." Furthermore, 1577 papers were found. After filtering for species, sex, language, and time range, 820 papers were left. The number of works included was 24 after title screening and 20 after abstract screening and full-text screening. EVIDENCE SYNTHESIS: More research will be needed to develop tools with an inclusive, non-judgmental, and open language capable of engaging the LGBTQ community. Cancer screening programs involve a large variety of healthcare providers including midwives. CONCLUSIONS: Midwives are multifaceted healthcare professionals whose large competence spectrum includes a variety of knowledge and skills going from antenatal care to education and research and they may efficiently provide cancer screenings. Midwives have been asking for more specialistic roles and calling for specific instruction to face the complex and ever-changing reality.

Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients.

BACKGROUND: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS. METHODS: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity. RESULTS: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus). CONCLUSIONS: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders.

BACKGROUND: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. HYPOTHESIS/OBJECTIVE: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). METHODS: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as Free Oxygen Radicals Test (FORT) and Free Oxygen Radicals Defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-ß, and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. RESULTS: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. CONCLUSION: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Case Report: Treatment of Kratom Use Disorder With a Classical Tricyclic Antidepressant.

Kratom or Mitragyna speciosa (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal. Its leaves are smoked, chewed, or infused, or ground to yield powders or extracts for use as liquids. It contains more than 40 alkaloids; among these, mitragynine and 7-hydroxymitragynine are endowed with variable mu, delta, and kappa opioid stimulating properties (with 7-hydroxymitragynine having a more balanced affinity), rhynchophylline, which is a non-competitive NMDA glutamate receptor antagonist, but is present in negligible quantities, and raubasine, which inhibits α1-adrenceptors preferentially over α2-adrenceptors, while the latter are bound by 7-hydroxymitragynine, while mitragynine counters 5-HT2A receptors. This complexity of neurochemical mechanisms may account for kratom's sedative-analgesic and stimulant effects. It is commonly held that kratom at low doses is stimulant and at higher doses sedative, but no cut-off has been possible to define. Long-term use of kratom may produce physical and psychological effects that are very similar to its withdrawal syndrome, that is, anxiety, irritability, mood, eating, and sleep disorders, other than physical symptoms resembling opiate withdrawal. Kratom's regulatory status varies across countries; in Italy, both mitragynine and the entire tree and its parts are included among regulated substances. We describe the case of a patient who developed anxiety and dysphoric mood and insomnia while using kratom, with these symptoms persisting after withdrawal. He did not respond to a variety of antidepressant combinations and tramadol for various months, and responded after 1 month of clomipramine. Well-being persisted after discontinuing tramadol.

Developmental trajectories in psychiatric disorders: does substance/alcohol use moderate the effects of affective temperaments as moderators of age at onset? A study in post-acute, hospitalized patients with psychotic or DSM-5 bipolar or major depressive disorders.

BACKGROUND: Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years ± 11.82 men, 43.21 years ± 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 ± 10.09 vs. 27.73 ± 10.35, respectively, p = 0.001, η2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 ± 4.08, p < 0.001, η2 = 0.069) and irritable (8.26 ± 4.69, p < 0.01, η2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (ß = -0.55, p < 0.005) and hyperthymic (ß = -0.95, p < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations. Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.

The effect of paliperidone palmitate long-acting injectable (PP-LAI) on "non-core" symptoms of schizophrenia: a retrospective, collaborative, multicenter study in the "real world" everyday clinical practice.

BACKGROUND: Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. AIM: The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. RESULTS: Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. DISCUSSION: The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. CONCLUSIONS: PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life.

BACKGROUND: To overcome nonadherence in patients with psychosis switch to long-acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus LAI comparisons showed similar antipsychotic responses. Psychoses often overlap with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto focused only on non-comorbid populations. OBJECTIVE: The objective of this study was to compare two LAIs, administered for 12 months, in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life (QoL) outcomes. PATIENTS AND METHODS: Inpatients were recruited during 2016 and switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients were discharged and followed up for 12 months. Patients were rated at baseline and after 1 year through the Clinical Global Impression scale - severity (CGIs), substance craving intensity was rated through a visual analog scale for substance craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We addressed confounders with backward stepwise logistic regression and three-way analysis of variance. RESULTS: PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM, but AM had a stronger craving for substances at baseline. Both LAIs were associated with significant improvements in all outcomes, with AM displaying stronger effect sizes than PP. The two groups did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year follow-up, AM fared better on all domains. The two groups did not differ in final severity, but PP scored higher than AM in craving at the 1-year endpoint.Limitation: The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias. CONCLUSION: 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity. AM, compared to PP, improved craving and QoL at the 1-year follow-up.

Nalmefene in Alcohol Use Disorder Subjects with Psychiatric Comorbidity: A Naturalistic Study.

INTRODUCTION: Nalmefene is the first drug to be approved for reducing alcohol consumption in alcohol use disorder (AUD) patients at high drinking risk. In real-world settings, there is a high prevalence of concurrent psychiatric disorders in AUD subjects, with associated increased morbidity and worse prognosis. This study evaluated the use of nalmefene in AUD patients with stabilized psychiatric comorbidity previously treated unsuccessfully for alcohol dependence, and assessed craving reduction and safety. METHODS: Sixty-five AUD outpatients treated with as-needed 18 mg nalmefene for 24 weeks were included. Primary outcome measures were: changes in heavy drinking days (HDDs) and total alcohol consumption (TAC, g/day). Secondary outcome measures were: changes in drinking risk level and craving (obsessive-compulsive drinking scale and visual analogue scale for craving). RESULTS: Forty-two AUD subjects (64.6%) had one or more stabilized psychiatric comorbidity. There was a significant reduction in HDDs, TAC and craving measures (p < 0.001), with no differences between subjects with and without psychiatric comorbidity. Nalmefene was safe and well tolerated in all patients. CONCLUSION: As-needed nalmefene reduced drinking and craving in AUD subjects with and without psychiatric comorbidity. These findings suggest that nalmefene is a valid therapeutic option in real-world clinical settings, where comorbid conditions are common, and has the potential to engage AUD patients who may otherwise not have sought help. FUNDING: Lundbeck Italia S.P.A.

Dreams and age.

This work evaluated the association of age and dream reports. The verbal reports of 148 dreams of elderly people (M age=75.8 yr.) were compared with 151 dreams of a group of young people (M age=22.0). The dreams were analyzed according to the Jungian vision (which looks at the dream as a text produced by the dreamer's unconscious while sleeping), using processing techniques derived from textual analysis. Significant differences were found between the number of words denoting emotion, with the young people reporting more explicit statements regarding emotional states. Significant differences were found also in use of verb tenses. When older people explicitly expressed an emotional state in a dream text, they shifted between present and past tense more frequently than young people. A significant prevalence in the semantic field of visual sense was evident as younger subjects used more sentences referring to sight than the elderly participants.

[Gambling Disorder: epidemiology, diagnosis, interpretative models and intervention]. / Disturbo da gioco d'azzardo: epidemiologia, diagnosi, modelli interpretativi e trattamento.

Gambling disorder is a frequently underdiagnosed and disabling disorder with a prevalence greatly increased in recent decades. For various reasons, only a small part of pathological gamblers seek a support making difficult an early identification and delaying the administration of appropriate treatment. In DSM-5, the disorder has been reclassified from an "Impulse-Control Disorder not elsewhere classified" to one of the "Substance-Related and Addictive Disorders" with the intention of improve the diagnosis, to better targeting the treatment and to stimulating further research efforts directed to the disorder. This article reviews assessment techniques, psychosocial and neurobiological factors in the development of pathological gambling and treatment strategies.

Intramuscular aripiprazole in the acute management of psychomotor agitation.

STUDY OBJECTIVE: To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation. DESIGN: Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response. SETTING: Acute psychiatric care wards in a single university hospital. PATIENTS: A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I). INTERVENTION: Aripiprazole 9.75 mg IM injection. MEASUREMENTS AND MAIN RESULTS: We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24 hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30 minutes. ACES improved after 90 minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2 hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure. CONCLUSION: Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time.

An improved simple LC-MS/MS method for the measurement of serum aripiprazole and its major metabolite.

BACKGROUND AND OBJECTIVES: Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection. METHOD: We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection. RESULTS: Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 ± 4.5% for Ar and 97.6 ± 7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs. CONCLUSION: Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods.