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Longitudinal psychopathological predictors of relapse in alcohol use disorder are unclear.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.At endpoint, 39% of patients maintained abstinence, 30.9% relapsed at ≤1 month from detoxification (early), 30.1% at1 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).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.

Abstract: 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 ob- served in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazo- done 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 de- pressive 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.

La pandemia da COVID-19 ha avuto un impatto particolar¬mente severo sulla salute mentale degli adolescenti. In questo lavoro, gli autori osservano che le manifestazioni di disagio emotivo sono emerse soprattutto a partire dell'autunno 2020, quando cioè le restrizioni si sono allentate ed è stato tentato un graduale ritorno all'incontro con l'Altro. Ed è proprio il timore dell'incontro con l'Alterità che sembrerebbe aver portato alla luce le profonde fragilità identitarie dei più giovani. Di una generazione che, alla continua ricerca di un Simile rassicurante, fatica a completare fisiologicamente il percorso di sog¬gettivazione, e in cui persino l'angoscia pare incapace di prendere una forma, in una continua e inafferrabile "erranza del sintomo".

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.

BackgroundMajor 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.MethodsWe 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.ResultsVortioxetine significantly improved mood in MDD + AUD patients (P 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 ConclusionsGiven 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.

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.

We present a new decoding algorithm based on error locating pairs and correcting an amount of errors exceeding half the minimum distance. When applied to Reed--Solomon or algebraic geometry codes, the algorithm is a reformulation of the so--called {\em power decoding} algorithm. Asymptotically, it corrects errors up to Sudan's radius. In addition, this new framework applies to any code benefiting from an error locating pair. Similarly to Pellikaan's and K\"otter's approach for unique algebraic decoding, our algorithm provides a unified point of view for decoding codes with an algebraic structure beyond the half minimum distance. It permits to get an abstract description of decoding using only codes and linear algebra and without involving the arithmetic of polynomial and rational function algebras used for the definition of the codes themselves. Such algorithms can be valuable for instance for cryptanalysis to construct a decoding algorithm of a code without having access to the hidden algebraic structure of the code.

Traumatic experiences during childhood may lead to the development of several psychiatric diseases, including mood disorders, different forms of psychosis, and post-traumatic stress disorders. Psychiatric patients with a history of childhood trauma (CT) show increased severity of symptoms, worse outcome, and poor treatment response. These features might be due to neurobiological, endocrinological, and immunological alterations occurring as a consequence of early exposure to stressors and mediated by the hypothalamus–pituitary–adrenal (HPA) axis. Pharmacological approach for the management of CT is usually employed as one component of integrated treatments, including psychotherapeutic and psychosocial interventions. However, subjects with CT often show inadequate response to different classes of psychiatric medications, especially antidepressants and mood stabilizers. Since a higher degree of activation of the immune system has been consistently observed both in psychiatric patients and in subjects exposed to early stressors, future research should test if immunomodulatory interventions could improve the treatment of psychiatric patients with a history of CT.

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.

Alcohol use disorder (AUD) represents a frequent comorbidity in patients with bipolar disorder (BD), with a prevalence rate of 30%–35%. AUD and BD show common genetic and neurophysiological pathways. Alcohol misuse negatively affects long-term mood stability, influencing several neurotransmitter functions and disrupting sleep architecture. Alcohol may also aggravate bipolar disorder neuro-progression via oxidative stress. Allostatic changes in the brain reward system may render BD patients more vulnerable to drug addiction. Patients with AUD-BD comorbidity show earlier onset, a more severe course of illness, higher impulsivity levels, worse treatment response, and increased suicide risk compared to patients with BD alone. Despite the prevalence and clinical impact of AUD-BD comorbidity, there is still a lack of evidence on effective treatments for patients with AUD and BD. Divalproex is the only medication that has been found significantly effective in reducing alcohol intake in bipolar patients. Psychotherapy and Integrated Group Therapy are also indicated.

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.

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 socio-demographic characteristics, cigarette smoking, alcohol and substance use, perceived academic performance, activities and behaviors (Internet use, gambling, physical exercising). The Internet Addiction Test (IAT), the South Oaks Gambling Screen - revised Adolescents (SOGS-rA), the Exercise Addiction Inventory - Short Form (EAI-SF) were administered to identify problematic behaviors. The Barratt Impulsiveness Scale Adolescent Version (BIS-11-A), the Snaith-Hamilton Pleasure Scale (SHAPS), the Dissociative Experience Scale for adolescents (A-DES), the Toronto Alexithymia Scale (TAS-20) 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), 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. Conclusions. Our study showed a relevant prevalence of addictive behaviors in a sample of Italian high school students, with specific gender differences. We underlined the co-occurrence 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.

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.

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.

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.

Background Dickkopf-1 (DKK1) is an inhibitor of the canonical Wnt pathway, which is known to be impaired in both psychotic and neurodegenerative disorders. Here, we examined serum DKK1 levels as an indicator of ongoing neurodegeneration in psychotic patients, with or without a recent or current history of drug abuse. Methods We measured serum DKK1 levels by ELISA in 22 inpatients with psychosis and no history of drug abuse, 22 with psychosis and drug abuse, and 16 controls. We rated psychopathology using the following rating scales: the Positive and Negative Syndrome Scale (PANSS); the Clinical Global Impressions (CGI) severity scale; and the Global Assessment of Functioning (GAF) scale. Extrapyramidal motor symptoms were assessed by the Simpson-Angus Neurological Rating Scale (NRS). Results Inpatients with psychosis and comorbid substance abuse showed significantly higher serum DKK1 levels than inpatients with psychosis and no comorbid substance abuse or controls. Comorbid patients had earlier onset, longer duration of psychosis, and more severe extrapyramidal motor symptoms. However, we did not find any significant correlation between DKK1 levels and rating scale scores. Conclusion Psychosis led to elevated serum DKK1 levels, and substance abuse led to a further increase. Knowing that there is a correlation between brain and blood levels of DKK1, we speculate that the observed increase in DKK1 levels reflects drug-induced neurotoxicity in our patients.

We examined the interaction between the selective serotonin reuptake inhibitor, fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor cells isolated from cultured cerebellar granule cells, considered as an in vitro model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3 receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R-APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the activation of 5-HT(1A) receptors. We found a strong synergism between fluoxetine and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The increased cell proliferation induced by fluoxetine+LY379268 was abrogated by the cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly, fluoxetine and LY379268 also acted synergistically in promoting neuronal differentiation when progenitor cells were incubated in the presence of serum. These data support the hypothesis that a combination between classical antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental treatment of depression.

Antidepressant drugs have a clinical latency that correlates with the development of neuroadaptive changes, including down-regulation of β-adrenergic receptors in different brain regions. The identification of drugs that shorten this latency will have a great impact on the treatment of major depressive disorders. We report that the time required for the antidepressant imipramine to reduce the expression of β-adrenergic receptors in the hippocampus is reduced by a co-administration with centrally active ligands of type 2/3 metabotropic glutamate (mGlu2/3) receptors. Daily treatment of mice with imipramine alone (10 mg/kg, i.p.) reduced the expression of β-adrenergic receptors in the hippocampus after 21 days, but not at shorter times, as assessed by western blot analysis of β1-adrenergic receptors and by the amount of specifically bound [3H]CGP-12177, a selective β-adrenergic receptor ligand. Down-regulation of β-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive. This intriguing finding suggests that neuroadaptation to imipramine – at least as assessed by changes in the expression of β1-adrenergic receptors – is influenced by drugs that interact with mGlu2/3 receptors and stimulates further research aimed at establishing whether any of these drugs can shorten the clinical latency of classical antidepressants

The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.

Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer’s disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies cast doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer’s disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder.

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.

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.

Group-II metabotropic glutamate receptor ligands as adjunctive drugs in the treatment of depression: a new strategy to shorten the latency of antidepressant medication?

Neuroinflammation has been proposed as a strong biological factor underlying the development of neuropsychiatric diseases. A role for dysregulation of the immune system was initially suggested in depressive disorders and subsequently extended to other illnesses, including bipolar disorder (BD). Indeed, there is growing evidence confirming the presence of a generalized pro-inflammatory state in BD patients, involving alterations in cytokine, acute-phase proteins, and complement factor secretion, white blood cell differentiation, microglial activation, arachidonic acid signaling pathways, and increased oxidative stress markers. Medications commonly used to treat BD, such as lithium, antiepileptics and antipsychotics, show some immunoregulatory activity both in vitro and in vivo. The aim of our study was to review the role of different inflammatory mechanisms, specifically in the development of excitatory symptoms, via a systematic PubMed search of the literature. Despite the high variability of results among studies, we found evidence indicating specific alterations of the inflammatory response during manic and mixed states of BD. These findings may help to clarify some of the complex mechanisms underlying the development of excitatory symptoms and suggest a potential role for drugs targeting the inflammatory system as new therapeutic options.

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.