Physical and cognitive correlates, inflammatory levels, and treatment response in post-COVID-19 first-onset vs. recurrent depressive episodes.

Psychiatric symptoms have been frequently reported in patients affected by COVID-19, both as new occurring and recurrences of pre-existing diseases. Depressive symptoms are estimated to affect at least 30% of patients following infection, with specific physical and cognitive features and relevant immune-inflammatory alterations. This study aimed to retrospectively characterize post-COVID-19 first-onset and recurrent major depressive episodes (MDE) and to evaluate the effects of antidepressants on physical and cognitive correlates of depression, in addition to mood, anxiety, and underlying inflammatory status. We evaluated 116 patients (44.8% males, 51.1 ± 17 years) with post-COVID-19 first-onset (38.8%) and recurrent (61.2%) MDE at baseline and after one- and three-month treatment with antidepressants (31% SSRIs, 25.9% SNRIs, 43.1% others). We assessed sociodemographic and clinical features and psychopathological dimensions through: Hamilton Depression and Anxiety Rating Scales; Short Form-36 Health Survey Questionnaire; Perceived Deficits Questionnaire-Depression 5-items. The systemic immune-inflammatory index was calculated to measure inflammation levels. Alongside the reduction of depression and anxiety (p < 0.001), physical and cognitive symptoms improved (p < 0.001) and inflammatory levels decreased (p < 0.001) throughout treatment in both groups. Post-COVID-19 recurrent MDE showed a significantly more severe course of physical and cognitive symptoms and persistently higher levels of inflammation than first-onset episodes. Antidepressants proved to be effective in both post-COVID-19 first-onset and recurrent MDE. However, a sustained inflammatory status might blunt treatment response in patients with recurrent depression in terms of physical correlates and cognition. Therefore, personalized approaches, possibly involving combinations with anti-inflammatory compounds, could promote better outcomes in this clinical population.

Effect of vortioxetine in subjects with major depressive and alcohol use disorders: a 6-month retrospective analysis.

BACKGROUND: Major depressive disorder (MDD) and alcohol use disorder (AUD) are highly comorbid, with greater clinical complexity and psychosocial impairment. Several antidepressants have been used in this population, with mixed results. This preliminary study aims to investigate the effects of the multimodal antidepressant vortioxetine in MDD + AUD subjects. METHODS: We retrospectively evaluated 57 MDD + AUD and 56 MDD outpatients, matched for baseline characteristics. Patients were assessed after 1, 3, and 6 months treatment with vortioxetine (10-20 mg/d, flexibly dosed) in combination with continuous psychosocial support. The primary outcome was improvement in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale. We also investigated changes in anxiety, anhedonia, cognition, functioning, quality of life, and clinical global severity using the following instruments: Hamilton Anxiety Rating Scale, Snaith-Hamilton Pleasure Scale, Digit Symbol Substitution Test, Perceived Deficits Questionnaire-Depression, Functioning Assessment Short Test, Quality of Life Index, and Clinical Global Impression-Severity Scale. RESULTS: Vortioxetine significantly improved mood in MDD + AUD patients (P < .001), with no differences when compared to MDD (P = .36). A substantial rate (45.6%) of comorbid subjects obtained clinical remission at endpoint (P = .36 vs MDD). We additionally observed baseline to endpoint improvements on all secondary outcomes (P < .001), with no significant difference between groups. Overall, vortioxetine was safe and well tolerated. CONCLUSIONS: Given its effectiveness on mood, cognition, and functioning, its good safety and tolerability profile, and low potential for abuse, vortioxetine could represent a valid pharmacological intervention in MDD + AUD patients as part of an integrated therapeutic-rehabilitation program.

Predictors of clinical severity in subjects attending the Emergency Department for substance use: a ten-year cross-sectional study.

OBJECTIVE: Substance-related referrals to the Emergency Department (ED) are rising. Multiple substance use is frequent, and psychiatric patients represent a high-risk population. Our study aimed at identifying risk factors for increased severity in ED attendances for substance use. METHODS: We retrospectively evaluated consecutive patients attending the ED over ten years for substance-related problems, subdivided according to the triage code as having a life-threatening (LT), potentially life-threatening (P-LT), and non-life-threatening (N-LT) condition. RESULTS: Substance/drug intake for deliberate self-harm was a risk factor for being classified as LT compared to both P-LT (OR = 6.357; p ≤ 0.001) and N-LT (OR = 28.19; p ≤ 0.001). Suicide attempts (OR = 4.435; p = 0.022) and multiple substance use (OR = 1.513; p = 0.009) resulted as risk factors for P-LT, compared to N-LT. Psychiatric diagnosis (OR = 1.942; p = 0.042) and multiple substance use (OR = 1.668; p = 0.047) were risk factors for being classified as LT rather than N-LT. CONCLUSIONS: In our sample, self-harming overdoses were the strongest risk factor for highest overall severity in a real-world setting. Psychiatric disorders and multiple substance use also increased the risk for greater severity at presentation. Substance use worsens patients' clinical picture and management, suggesting the need for consultation-liaison psychiatry services in emergency contexts and highlighting the role of EDs as key sites for identification and early intervention.

Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus.

Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the prefrontal cortex or corpus striatum, as compared to both groups of control rats. No changes in the expression of mGlu3 receptor mRNA levels or mGlu1α and mGlu5 receptor protein levels were found with exception of an increase in mGlu1α receptor levels in the striatum of SD rats. Moving from these findings we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA (30mg/kg, i.p.). SD rats were also treated with sodium valproate (300mg/kg, i.p.) as an active comparator. Both BINA and sodium valproate were effective in reversing the manic-like phenotype evaluated in an open field arena in SD rats. BINA treatment had no effect on motor activity in control rats, suggesting that our findings were not biased by a non-specific motor-lowering activity of BINA. These findings suggest that changes in the expression of mGlu2 receptors may be associated with the enhanced motor activity observed with mania.

Childhood sexual abuse and suicide attempts in patients with substance use disorders: The mediating role of emotion dysregulation.

BACKGROUND: Suicide attempts (SA) are a public health concern because of increasing prevalence and clinical implications. Childhood trauma (CT) and emotion dysregulation (ED) have been proposed as predictors of SA, but few data are available in patients with Substance Use Disorder (SUD). OBJECTIVE: Our study aims to investigate the association of sociodemographic/clinical variables, CT typologies, and ED features with SA in SUD patients. PARTICIPANTS AND SETTING: Subjects with SUD were screened in an outpatient setting. The final sample consisted of 226 patients, subdivided according to the presence of lifetime SA (SUD, n = 163 vs. SUD-SA, n = 63). METHODS: Participants were compared for sociodemographic and clinical information. CT and ED were assessed through the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Difficulties in Emotion Regulation Scale (DERS), respectively. We performed a mediation analysis to test the effect of CT and ED on SA. RESULTS: Patients with a history of SA (27.9 %) displayed more psychiatric comorbidities (p = 0.002) and hospitalizations (p < 0.001), higher scores at CTQ-SF sexual abuse (p < 0.001) and DERS 'impulse' (p = 0.002), 'goals', 'non-acceptance', 'strategies' (p < 0.001) subscales. The relationship between CTQ-SF sexual abuse and SA was significantly mediated by DERS 'strategies' (p = 0.04; bootstrapped 95 % LLCI-ULCI = 0.004-0.024). CONCLUSIONS: CT and different dimensions of ED were associated with SA in SUD patients. In our sample, the effects of childhood sexual abuse on SA were mediated by limited access to emotion regulation strategies. SUD patients are burdened with higher all-cause mortality, and CT and lifetime SA can worsen clinical outcomes. Clarifying the reciprocal interactions of psychopathological dimensions may help deliver targeted interventions and reduce suicide risk in specific populations.

Neurodevelopment in schizophrenia: the role of the wnt pathways.

OBJECTIVES: To review the role of Wnt pathways in the neurodevelopment of schizophrenia. METHODS: SYSTEMATIC PUBMED SEARCH, USING AS KEYWORDS ALL THE TERMS RELATED TO THE WNT PATHWAYS AND CROSSING THEM WITH EACH OF THE FOLLOWING AREAS: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action. RESULTS: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established. CONCLUSIONS: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.

Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone.

BACKGROUND: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. METHODS: One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. RESULTS: Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. CONCLUSION: Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.

Impulsivity and alexithymia predict early versus subsequent relapse in patients with alcohol use disorder: A 1-year longitudinal study.

INTRODUCTION: Longitudinal psychopathological predictors of relapse in alcohol use disorder are unclear. METHODS: Relapses, sociodemographic and psychopathological risk factors were assessed in 171 alcohol use disorder outpatients within a 1-year follow up. Impulsivity and alexithymia were evaluated using the Barratt Impulsiveness Scale and the Toronto Alexithymia Scale, respectively. RESULTS: At endpoint, 39% of patients maintained abstinence, 30.9% relapsed at ≤1 month from detoxification (early), 30.1% at >1 month (subsequent). Baseline Barratt Impulsiveness Scale score was predictive of early versus subsequent relapse (odds ratio 1.12, p = 0.005) and versus abstinence (odds ratio 1.17, p < 0.001). Toronto Alexithymia Scale score was a risk factor for subsequent versus early relapse (odds ratio 1.13, p = 0.003) and versus abstinence (odds ratio 1.21, p < 0.001). DISCUSSION AND CONCLUSIONS: Impulsivity predicted relapse within the first 4-weeks; alexithymia showed delayed effects. Time-varying effects of specific relapse factors emphasise the need for preliminary careful assessment and personalised interventions to promote long-term abstinence.

Predictors of polysubstance use in patients with severe alcohol use disorder: the role of reward craving.

BACKGROUND: Different craving typologies (i.e., reward, relief, obsessive) have been identified in alcohol use disorder (AUD) but have been less investigated in specific populations like AUD patients with polysubstance use (PSU). The role of dysfunctional personality traits and reward pathways has been reported in both AUD and PSU. We hypothesized that patients with AUD-PSU might show a prevalent reward craving, alongside specific sociodemographic, clinical, and personality features, and aimed at investigating differences in 423 severe AUD outpatients with and without PSU. METHODS: One hundred fifteen patients (27.1% of the sample, 67% males, 42 ± 11.6 years old) displayed PSU. Sociodemographic, clinical features and psychopathological/personality dimensions were assessed through: Craving Typologies Questionnaire (CTQ); Obsessive-Compulsive Drinking Scale (OCDS); UPPS-P Impulsive Behavior Scale (S-UPPS-P); Difficulties in Emotion Regulation Scale (DERS). A binomial logistic regression explored factors associated with PSU. RESULTS: We found higher CTQ 'reward' scores (p < 0.001) in AUD-PSU patients, and a significant association between reward craving and PSU through logistic regression (OR:1.13; p = 0.005). Earlier AUD onset (p < 0.001), greater rates of binge drinking (p = 0.029), more legal problems (p = 0.015), but no significantly higher S-UPPS-S and DERS scores, were detected in AUD-PSU patients. CONCLUSIONS: Reward craving was associated with increased risk for PSU in severe AUD patients. Given AUD-PSU participants greater severity and detrimental treatment responses imputed to PSU, identifying prevalent craving types among risk factors for PSU in AUD may help to implement therapeutic strategies. Addressing neurobiological and behavioral mechanisms through combined psychotherapies, pharmacological and neuromodulation treatments could support tailored interventions with better long-term outcome.

The wnt pathway in mood disorders.

OBJECTIVES: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders. METHODS: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion. RESULTS: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders. CONCLUSIONS: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.

Integrating Psychophysiology within Clinical Practice: A Pilot Cross-sectional Study on Prodromal Symptoms of Schizophrenia, Emotion Regulation, and Personality Functioning.

OBJECTIVE: To investigate the association between prodromal symptoms of schizophrenia, autonomic activity, and personality functioning. METHOD: 10 adolescents underwent semi-structured interviews assessing prodromal symptoms of schizophrenia and personality functioning. Cardiac activity was recorded at baseline, during the clinical interviews, and at recovery to assess concurrent changes in autonomic functioning. RESULTS: During the assessment of prodromal symptoms of schizophrenia, participants increased sympathetic activation compared to the recovery condition, and reduced vagal activation compared to the assessment of interpersonal functioning. CONCLUSIONS: The findings highlight the importance of integrating the autonomic assessment in clinical psychiatric and psychological practice.

Mixed States in Patients with Substance and Behavioral Addictions.

Mixed affective states occur in approximately 40% of patients with mood disorders and are burdened with a significant rate of comorbidities, including addictive disorders (AD). The co-occurrence of mixed features and AD represents a challenge for clinicians because the reciprocal, negative influence of these conditions leads to a worse course of illness, treatment resistance, unfavorable outcome, and higher suicide risk. This article discusses clinical presentation, possible common pathogenetic pathways, and treatment options. Further investigations are required to clarify the determinants and the implications of this co-occurrence, and to detect suitable approaches in clinical management.

Sensitivity to Climate and Weather Changes in Euthymic Bipolar Subjects: Association With Suicide Attempts.

BACKGROUND: Climate and weather are known to affect multiple areas of human life, including mental health. In bipolar disorder (BD), seasonality represents an environmental trigger for mood switches, and climatic variables may contribute to recurrences. Several studies reported seasonal and climatic-related variations in the rate of suicide attempts. Suicide risk is relevant in BD, with approximately 25% of patients attempting suicide. Therefore, this study aimed to assess sensitivity to weather and climatic variations in BD subjects and its relationship with lifetime suicide attempts. METHODS: Three hundred fifty-two euthymic BD and 352 healthy control subjects, homogeneous with respect to socio-demographic characteristics, were enrolled. All participants were administered the METEO-Questionnaire (METEO-Q) to evaluate susceptibility to weather and climatic changes. We also investigated the potential relationship between sensitivity to climate and weather and lifetime suicide attempts in BD patients. RESULTS: METEO-Q scores and the number of subjects reaching the cut-off for meteorosensitivity/meteoropathy were significantly higher in BD patients. Within the clinical group, BD subjects with lifetime suicide attempts obtained higher METEO-Q scores, with no differences between BD-I and BD-II. The number of suicide attempts directly correlated with METEO-Q scores. The presence of suicide attempts was associated with the physical and psychological symptoms related to weather variations. DISCUSSION: Our findings support the relevance of sensitivity to weather and climate variations in a large sample of BD subjects and point out the association of this feature with lifetime suicide attempts.

Pharmacological and Psychosocial Treatment of Adults With Gambling Disorder: A Meta-Review.

BACKGROUND AND OBJECTIVES: Gambling disorder (GD) leads to impaired socioeconomical functioning and increased social costs. Although the research on GD has been rising over the years, approved treatment guidelines are currently not available. The aim of this study was to systematically review the literature on the pharmacological and psychosocial treatment of adults with GD, and to identify possible agreed-upon standards of care. METHODS: MEDLINE, PubMed, Cochrane, Web of Science, Embase, and CINAHL electronic databases were searched up to April 2019 for systematic reviews on pharmacological, psychosocial, and combined treatment of adults with GD. Twenty-six studies were eventually included in this meta-review. RESULTS: Studies reported promising results of opioid antagonists and mood stabilizers in reducing GD-related symptomatology. Lithium was particularly effective in subjects with comorbid bipolar disorders. Cognitive behavioral therapy (CBT) was the most commonly used psychological intervention and reduced global severity, gambling frequency, and financial loss. Motivational interviewing (MI) seemed to improve several GD domains, alone or in combination with CBT. Self-help interventions (SHIs) showed some efficacy in promoting treatment-seeking, and in combination with other treatments. CONCLUSIONS: We found moderate evidence of effect for CBT, but weaker evidence for pharmacotherapy and SHIs. Results suggested some efficacy for MI in the short but not in the long term. It is likely that certain interventions might be more effective than others on specific features of GD. Further studies are needed to compare the efficacy and acceptability of individual and combined psychosocial and pharmacological interventions, to deliver patient-tailored treatments.

Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine.

Recent studies have implicated brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression and the activity of antidepressant drugs. Serum BDNF levels are lower in depressed patients, and increase in response to antidepressant medication. However, how BDNF responds to different classes of antidepressant drugs is unknown. We assessed serum BDNF levels in 21 patients with major depressive episode treated with sertraline, escitalopram, or venlafaxine and 20 healthy controls. Serum samples were collected between 10 a.m. and 12 p.m. at baseline, 5 weeks, and 6 months of treatment. BDNF levels were measured via immunoassay. The severity of symptoms and response to treatment were assessed by the Hamilton rating scales for depression (HRSD). Baseline serum BDNF levels were significantly lower in depressed patients compared to controls. Sertraline increased BDNF levels after 5 weeks and 6 months of treatment. Venlafaxine increased BDNF levels only after 6 months. Escitalopram did not affect BDNF levels at either time point. A significant negative association was found between percentage increase in BDNF levels and percentage decreased in HRSD scores after 6 months of treatment. In conclusion, these results suggest that different antidepressant drugs have variable effects on serum BDNF levels. This is true even though the three different drugs were equally effective in relieving symptoms of depression and anxiety.

Childhood trauma and resilience in psoriatic patients: A preliminary report.

AIMS: Psoriasis is a chronic inflammatory skin disease with a complex etiology, involving the immune system, genetic factors, and external/internal triggers, with psychosomatic aspects. The aim of the study was to investigate childhood trauma and resilience in a psoriatic sample compared with healthy controls. Correlations between childhood trauma, resilience, quality of life, clinical data and psoriatic features were also evaluated. METHODS: Seventy-seven psoriatic patients and seventy-six homogeneous healthy controls were enrolled. We used the Psoriasis Area and Severity Index (PASI) to assess the severity of psoriasis and the Skindex-29 to measure health-related quality of life. The psychometric battery included the Childhood Trauma Questionnaire (CTQ) and the Connor-Davidson Resilience Scale (CD-Risc) to assess trauma exposure and resilience, respectively. RESULTS: Psoriatic patients showed a significant prevalence of childhood trauma and a lower resilience level compared to healthy controls. Associations between traumatic experiences, low resilience and reduced quality of life in psoriatic subjects were also observed. CONCLUSIONS: A multidisciplinary approach is helpful to investigate clinical aspects, trigger factors and psychophysiological stress response in psoriatic subjects. Improving resilience with an early psychological intervention focused on self-motivation and strengthening of self-efficacy could facilitate the management of psoriasis.

Gender Differences and Psychopathological Features Associated With Addictive Behaviors in Adolescents.

BACKGROUND: The aims of the study were to assess prevalence and gender differences of addictive behaviors (substance- and non-substance-related) in an adolescent population, and their association with psychopathological features and academic performance. MATERIAL AND METHODS: A sample of high school Italian students (n = 996; M = 240, F = 756) was examined using a self-report survey concerning sociodemographic characteristics, cigarette smoking, alcohol and substance use, perceived academic performance, activities, and behaviors (Internet use, gambling, and physical exercising). The Internet Addiction Test, the South Oaks Gambling Screen-revised Adolescent, and the Exercise Addiction Inventory-Short Form were administered to identify problematic behaviors. The Barratt Impulsiveness Scale for Adolescent, the Snaith-Hamilton Pleasure Scale, the Dissociative Experience Scale for Adolescent, and the Toronto Alexithymia Scale were used to investigate psychopathological dimensions. RESULTS: Frequent alcohol intake and lifetime substances consumption were more common among males. The occurrence of other addictive behaviors was 22.1% for problematic Internet use (M = F), 9.7% for at-risk/problematic gambling (M > F), and 6.2% for maladaptive physical exercise (M = F). We also found an association between substance-/non-substance-related addictive behaviors and psychopathological dimensions. Addictive behaviors were more frequent among students reporting poor school performance. CONCLUSION: Our study showed a relevant prevalence of addictive behaviors in a sample of Italian high school students, with specific gender differences. We underlined the cooccurrence of substance and non-substance-related addictive behaviors, and their association with worse school performance. Dissociative proneness, anhedonia, alexithymia, and impulsivity were associated with addictive behaviors in adolescents and might represent vulnerability factors for the development of psychiatric disorders in adulthood. A better understanding of psychopathological features associated with addictive behaviors might be useful for the prevention/early intervention.

Neurobiological Evidence for the Primacy of Mania Hypothesis.

BACKGROUND: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania. OBJECTIVE: To identify evidence in literature that supports or falsifies this hypothesis. METHOD: We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies. RESULTS: Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so. LIMITATIONS: Only few studies compared manic with depressive phases, with the majority including patients in euthymia. CONCLUSION: It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.

Metabotropic Glutamate 2/3 Receptors and Epigenetic Modifications in Psychotic Disorders: A Review.

Schizophrenia and Bipolar Disorder are chronic psychiatric disorders, both considered as "major psychosis"; they are thought to share some pathogenetic factors involving a dysfunctional gene x environment interaction. Alterations in the glutamatergic transmission have been suggested to be involved in the pathogenesis of psychosis. Our group developed an epigenetic model of schizophrenia originated by Prenatal Restraint Stress (PRS) paradigm in mice. PRS mice developed some behavioral alterations observed in schizophrenic patients and classic animal models of schizophrenia, i.e. deficits in social interaction, locomotor activity and prepulse inhibition. They also showed specific changes in promoter DNA methylation activity of genes related to schizophrenia such as reelin, BDNF and GAD67, and altered expression and function of mGlu2/3 receptors in the frontal cortex. Interestingly, behavioral and molecular alterations were reversed by treatment with mGlu2/3 agonists. Based on these findings, we speculate that pharmacological modulation of these receptors could have a great impact on early phase treatment of psychosis together with the possibility to modulate specific epigenetic key protein involved in the development of psychosis. In this review, we will discuss in more details the specific features of the PRS mice as a suitable epigenetic model for major psychosis. We will then focus on key proteins of chromatin remodeling machinery as potential target for new pharmacological treatment through the activation of metabotropic glutamate receptors.