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The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients' perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients' view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith-Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients' and clinicians' perspectives, although with some differential effects on specific symptoms at given time-points. Including patients' viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.

Background: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine., Methods: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI)., Findings: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores., Conclusions: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted., Competing Interests: M.D.N. is/has been a consultant and/or a speaker for and/or has received research grants from: Angelini, Idorsia Pharmaceuticals, Janssen, Lundbeck, Neuraxpharma, Otsuka. G.S. is/has been a consultant and/or a speaker for and/or has received research grants from: Angelini, Janssen, Lundbeck, Neuraxpharma, and Otsuka. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The COVID-19 pandemic, which has affected a significant number of individuals worldwide, is generating serious mental health issues. Recovered COVID-19 patients have experienced traumatic events related to their symptoms, isolation, possible hospitalization, bereavement, fear of infecting loved ones and the physical consequences of COVID-19. One effective psychological treatment for these patients is Eye Movement Desensitization and Reprocessing (EMDR). The aim of this paper is to describe the therapeutic intervention and effects of EMDR in a pool of COVID-19 survivors referred to an integrated psychological/psychiatric outpatient service. Twelve patients, comprising of nine males and three females, underwent EMDR psychotherapy from October 2020 to February 2022. Each patient received 8-16 weekly treatment sessions. The standard EMDR protocol of eight stages was administered to enable desensitization and reprocessing of four main targets: first positive swab, hospitalization, isolation and fear for relatives' health. Efficacy of EMDR was demonstrated by the significant improvement at clinical scale for subjective distress caused by traumatic events. For the therapists, carrying out these treatments was an intense and challenging experience. In fact, the perceived distance between therapist and patient was less defined than in other hospital settings because the pandemic affects everyone equally. However, with the widespread availability of vaccines and although the pandemic is still ongoing with the emergence of new variants, a window of improvement in the mental health landscape is starting to open up., (© 2022 John Wiley & Sons, Ltd.)

(1) Background: During the SARS-CoV-2 (COVID-19) pandemic, cannabis use increased relative to pre-pandemic levels, while forced home confinement frequently caused sleep/wake cycle disruptions, psychological distress, and maladaptive coping strategies with the consequent appearance of anxiety symptoms and their potential impact on substance use problems. (2) Aim: Long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. The present work aims to investigate the effectiveness of trazodone in optimizing the condition of people with cannabis dependence under pandemic conditions. (3) Methods: All cases with cannabis use disorder were uniformly treated with long-acting trazodone 150 mg or 300 mg/day; their craving and clinical status were monitored through appropriate psychometric scales. Side effects were recorded as they were reported by patients. We described the cases of three young patients-one man and two women-who were affected by chronic cannabis use disorder and who experienced lockdown-related psychological distress and sought psychiatric help. (4) Results: The described cases highlight that the once-a-day formulation of trazodone seems to have a therapeutic role in patients with cannabis use disorder and to guarantee tolerability and efficacy over time. No significant side effects emerged. (5) Conclusions: The use of long-acting trazodone (150 mg or 300 mg daily) has a potential benefit as monotherapy in patients with cannabis use disorder. Trazodone deserves to be studied in terms of its efficacy for cannabis use disorder.

Functional movement disorders (FMD) involve a broad range of abnormal involuntary movements not consistent with neurological diseases. These conditions often occur in combination with mood and anxiety disorders and are associated with poor clinical outcomes. We report the case of a 57-year-old woman diagnosed with treatment-resistant depression (TRD) and comorbid FMD treated with weekly intranasal administrations of esketamine over a six-month follow-up period. A comprehensive clinical and psychometric assessment was carried out at different time points. After 2 months of treatment, a complete remission of motor and axial functional disturbances (athetosis, trunk torsion and genuflections) was detectable, along with a progressive improvement in depressive symptoms during follow-up until full remission. According to novel lines of evidence, glutamatergic transmission might play a role in the pathophysiology of FMD through aberrant limbic-motor interactions. We report that treatment with esketamine, a noncompetitive N-methyl-d-aspartate glutamatergic receptor antagonist, was associated with remission of FMD symptoms in a patient with TRD. Pharmacological compounds modulating brain glutamatergic activity may be of potential benefit in the clinical management of FMD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Major depressive disorder (MDD) has different clinical presentations and is associated with neurobiological alterations. Hopelessness, anhedonia, and dissociation represent some of the most pervasive psychopathological symptoms that often lead to suicidal thoughts, attempts, and actions. To further research on the concept of depression endophenotypes, this study aimed to assess the possible relationships between hopelessness and other clinical and biological correlates (i.e., striatal dopaminergic dysfunction) in depressed patients. Methods: We recruited 51 subjects with MDD. All subjects underwent 123 I-FP-CIT SPECT to assess striatal dopamine transporter (DAT) availability and a psychometric evaluation using the psychometric scale to assess depressive, anxious, dissociative, and hopelessness symptoms aside from suicidal ideation. Result: An inverse correlation between the hopelessness score and dopamine transporter availability in all basal ganglia was bilaterally found. (Right Putamen, r = -0.445, p < 0.01; Left Putamen, r = -0.454, p < 0.01; Right Caudate, r = -0.398, p < 0.01; Left Caudate, r = -0.467, p < 0.01) Moreover, a positive correlation was also found between hopelessness and dissociative symptoms. Conclusions: These results provide important evidence on the neurobiological and clinical correlates of different psychopathological symptoms of depression with potential implications in terms of devising more effective treatment programs.

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., (Copyright © 2020 Di Nicola, Mazza, Panaccione, Moccia, Giuseppin, Marano, Grandinetti, Camardese, De Berardis, Pompili and Janiri.)

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed 123 I-FP-CIT Single-photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward-based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (-13.30% in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down-regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system., (© 2018 Society for the Study of Addiction.)

Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15 Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Aim of the study was the validation of the Bipolar Disorder Rating Scale (BDRS) in an Italian population. Secondary aim was the evaluation of differences between unipolar and bipolar depression and between bipolar I and II depressed patients. Method: 125 Bipolar Disorder and 60 Major Depressive Disorder patients were administered an Italian translation of the BDRS (I-BDRS), Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Temperament and Character Inventory-Revised (TCI-R). Results: I-BDRS showed considerable validity and reliability. Factor analysis found 3 subscales, two linked to depressive symptoms and one to mixed symptoms. Measures concerning depression (MADRS and HAM-D) were positively related to the I-BDRS's subscales, but mostly to the two subscales measuring depression. In mixed symptoms, the mean of the bipolar group was significantly higher than the unipolar group suggesting that the BDRS was able to distinguish between unipolar and bipolar depressed patients. Conclusion: I-BDRS is a valid scale for the measurement of depression in BD patients, with a notable internal consistency (Cronbach's α 0.82), a significant consistency between items/total (Cronbach's α from 0.80 to 0.82) and positive correlation with other scales (MADRS r = 0.67, p < 0.001; HDRS r = 0.81, p < 0.001; YMRS r = 0.46 p < 0.0001). The mixed state sub-scale shows usefulness in differentiating bipolar from unipolar patients. I-BDRS could be a sensitive tool, both in pure depression and in mixed states, and could be used in the everyday screening and treatment of Bipolar Disorder.

The present study describes a new mixed program of psychoeducational and psychological interventions for bipolar patients, applicable during everyday practice. Thirty-two bipolar patients recruited at a psychiatric day-hospital service have been admitted to a program consisting of 30 meetings and 2 follow-ups at 6 and 12 months. The psychoeducational support determined a general improvement of all included patients. At baseline, patients with residual depression had higher Hamilton Depression Rating Scale (HDRS) scores than euthymic patients (mean score ± SD: 21.25 ± 3.92 vs. 7.00 ± 2.95, respectively). After psychoeducation sessions, the HDRS scores of euthymic patients remained stable (mean ± SD: 7.00 ± 3.74), whereas the HDRS scores of depressed patients demonstrated a statistically significant improvement (mean ± SD: 14.00 ± 6.72, t = 2.721, p = 0.03). Results of the Connor-Davidson Resilience scale and specifically constructed questionnaire Questionario per la Valutazione della Conoscenza e dell'Apprendimento per il Disturbo Bipolare showed a statistically significant improvement in resilience and insight in all recruited patients. Psychoeducational intervention as adjunctive treatment to pharmacotherapy seems to be very effective in bipolar patients, not only for those in the euthymic phase, but this model could also be extended to patients with an ongoing mild or moderate depressive episode.

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.5) or SHAM (n.6) treatment. Clinical and SPECT evaluations were then carried out after four weeks of rTMS sessions (T1). At baseline, AUD patients showed higher striatal DAT availability than healthy control subjects (HC). Patients receiving the REAL stimulation revealed a reduction in DAT availability at T1, whereas the SHAM-treated group did not. In addition, patients receiving the REAL stimulation had a decrease in alcohol intake. The results of this longitudinal pilot study may suggest a modulatory effect of deep rTMS on dopaminergic terminals and a potential clinical efficacy in reducing alcohol intake in AUD patients. Further investigations are required to confirm these preliminary data., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Background: Recently there is increasing recognition of cognitive dysfunction as a core feature of Major Depressive Disorder (MDD). The goal of the current meta-analysis was to review and examine in detail the specific features of cognitive dysfunction in Melancholic (MEL) versus Non-Melancholic (NMEL) MDD., Methods: An electronic literature search was performed to find studies comparing cognitive performance in MEL versus NMEL. A meta-analysis of broad cognitive domains (processing speed, reasoning/problem solving, verbal learning, visual learning, attention/working memory) was conducted on all included studies (n=9). Sensitivity and meta-regression analyses were also conducted to detect possible effects of moderator variables (age, gender, education, symptom severity and presence of treatments)., Results: MEL patients were older and more severly depressed than NMEL subjects. The MEL group was characterized by a worse cognitive performance in attention/working memory (ES=-0.31), visual learning (ES=-0.35) and reasoning/problem solving (ES=-0.46). No difference was detected in drug-free patients by sensitivity analyses. No effect was found for any of our moderators on the cognitive performance in MEL vs NMEL., Conclusion: Our findings seem to support a moderate but specific effect of melancholic features in affecting the cognitive performance of MDD, in particular as regards visual learning and executive functions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Mismatch negativity (MMN) is thought to reveal several abnormalities of cognitive functioning. Although depression often affects cognitive functioning, previous studies concerning MMN in depressed patients provided conflicting results. In recent reports, it has been suggested that depressed patients may show abnormal auditory response to regular auditory stimuli presented with at a relatively high intensity. We thus recorded acoustic MMN in 16 drug-free patients suffering from moderate depression and in 10 healthy subjects at 2 different stimulus intensities. Differences in MMN latency and amplitude between depressed patients and healthy subjects reached the significance level only for high intensity stimulation, and they were consistent with a dysfunction of frontal MMN subcomponents in depressed patients. This finding suggests that consistent MMN abnormalities can be observed in depressed patients by using high-intensity stimulation; moreover, it supports the hypothesis of disturbances of frontal networks in depression even in early stages of disease., (© EEG and Clinical Neuroscience Society (ECNS) 2015.)

Background and Aims: This study aimed to test the effectiveness of an individualized, integrated, day-care treatment programme for the acute phase of "difficult-to-treat depression" (DTD) in a sample of bipolar and unipolar subjects with a complex co-morbidity pattern., Methods: A total of 291 patients meeting criteria for DTD were consecutively recruited. All participants underwent a 12-week day-care intervention including individual psychological support and group psycho-education. Subjects were assessed for depressive symptom severity by the 21-item Hamilton Depression Rating Scale (HDRS) at the baseline (T0) and after 4 (T1) and 12 (T2) weeks of treatment. A repeated measures general linear model was performed to test for interactive effects among variables., Results: An overall significant improvement was detected in the majority of cases (F = 138.6, p < 0.0001). Responders reported lower rates of personality disorders and higher baseline depressive severity. An interaction between bipolarity and co-morbidity was associated with a poorer outcome (F = 5.9, p = 0.0034). Family involvement was the only significant predictor for symptom improvement (F = 7.9, adjusted p = 0.0025)., Conclusions: Our intervention proved to be effective in the treatment of complex and severe forms of depression. Our results on the role of family support require further investigation to better define suitable targets for tailored therapeutic approaches.

Aim: Aim of this study was to evaluate the association between attachment style, compliance, quality of life and renal function in adult patients after kidney transplantation., Methods: A total of 43 adult patients who received a kidney transplant more than 3 months before were enrolled and were asked to complete two Self-Report questionnaires: Attachment Style Questionnaire (ASQ-40) and Short Form Health Survey (SF-36). Also compliance was measured using appropriate questions., Results: Linear regression analysis showed associations between the confidence in relationships (ASQ-40) and compliance [beta = -0.37; B = -0.02; t(41) = -2.51; p = 0.02]; aspects of anxious attachment style (ASQ-40) and creatinine levels [beta = 0.3; B = 0.13; t(41) = 2.03; p = 0.04]; aspects of avoidant attachment style (ASQ-40) and compliance [beta = -0.37; B = -3.15; t(41) = -2.35; p = 0.02]. Patients who exhibited avoidant attachment had a significantly better perception of their own general health than patients with anxious [F(2,37) = 6.8; p < 0.05] or secure attachment; however, they had a worse perception regarding role limitations due to emotional problems, compared to patients with anxious attachment [F(2,37) = 6.4; p < 0.05]., Discussion: The results of this study suggest that the evaluation of the attachment style in adult kidney transplant patients can contribute to plan a goal-directed psychological support program for these patients, in order to increase their compliance. The association between aspects of anxious attachment style and creatinine level needs more investigations.

Unlabelled: Recent studies show that alexithymia may influence compliance and quality of life in different clinical situations. The aim of this study was to evaluate the associations between alexithymia or emotional self-efficacy and compliance, quality of life (QoL) and renal function in renal transplant patients., Methods: Forty-three patients were enrolled during a follow-up visit (>3 months post-transplant) and were asked to complete three self-report questionnaires (TAS-20, SF-36, RESE) to answer the following items: "In the past four weeks, how many times did you fail to take your prescribed dose?" and "How would you rate your adherence levels from 0 to 100?" (visual analogue scale)., Results: Alexithymia was positively correlated with non-compliance (r=.314; p=.04), and negatively with QoL dimensions. Analysis of variance confirmed that patients with high levels of alexithymia reported a negative perception of their QoL (mental health: F(1,41)=7,6; p=.008) and lower levels of compliance (F(1,41)=12,5; p=.001) compared with patients with low levels of alexithymia. The self-efficacy in the management of negative emotions was significantly correlated (r=-.314; p=.04) with creatinine levels and positively with the QoL (mental health: r=.421; p=.005)., Discussion: The inability to recognize and express emotions, as well as the ability to manage negative emotions, may influence compliance and QoL of renal transplant patients. Focused psychological support could be useful in these patients in order to increase their compliance and QoL., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The goal of the current meta-analysis was to review and examine in detail the features of cognitive performance in psychotic (MDDP) versus non-psychotic (MDD) major depressive disorder., Methods: An electronic literature search was performed to find studies comparing cognitive performance in MDDP versus MDD. A meta-analysis of broad cognitive domains (processing speed, reasoning/problem solving, verbal learning, visual learning, attention/working memory) and individual cognitive tasks was conducted on all included studies (n=12). Demographic and clinical features were investigated via meta-regression analysis as moderators of cognitive performance., Results: No difference in socio-demographic and clinical variables was detected between groups. In general, a poorer cognitive performance was detected in MDDP versus MDD subjects (ES=0.38), with a greater effect size in drug-free patients (ES=0.69). MDDP patients were more impaired in verbal learning (ES=0.67), visual learning (ES=0.62) and processing speed (ES=0.71) tasks. A significantly poorer performance was also detected in MDDP patients for individual tasks as Trail Making Test A, WAIS-R digit span backward and WAIS-R digit symbol. Age resulted to have a negative effect on tasks involved in working memory performance., Conclusion: In line with previous meta-analyses, our findings seem to support an association between psychosis and cognitive deficits in the context of affective disorders. Psychosis during the course of MDD is associated with poorer cognitive performance in some specific cognitive domains, such as visual and verbal learning and executive functions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and affective disorders has been consistently reported in adults. Less data regarding the role of personality traits and the influence of ADHD co-occurrence on clinical characteristics and outcome of mood disorders are currently available. One hundred and six remitted major depressed, 102 euthymic bipolar subjects, and 120 healthy controls, homogeneous with respect to demographic characteristics, were included in the study. ADHD diagnosis was based on DSM-IV-TR criteria. Childhood and adult ADHD features were measured with the Wender Utah Rating Scale, the Adult ADHD Self-rating Scale, and the Brown Attention-Deficit Disorder Scale. The Revised NEO Personality Inventory was also administered to the clinical groups, in order to investigate personality dimensions. The occurrence of adult ADHD in subjects with bipolar disorders (BD) or major depressive disorder (MDD) was 15.7 and 7.5 %, respectively, compared to 3.3 % in healthy controls (HC). Significant associations (p < .001) between personality traits (neuroticism, conscientiousness, and extraversion) and ADHD features were observed. Logistic regression analysis of all clinical subjects (n = 208) showed that those with lower levels of neuroticism (OR = 1.031; p = .025) had a lower frequency of ADHD comorbidity. The present study emphasizes the close relationship between affective disorders, especially BD, and ADHD in adults. Our findings support the need to assess subjects with mood disorders in the clinical setting for possible coexisting ADHD and to further investigate personality traits to better understand the etiology of affective disorders and ADHD co-occurrence.

Background: The co-occurrence of bipolar disorder (BD) and gambling disorder (GD), though of clinical and public health importance, is still scarcely investigated. Comorbid BD-GD subjects experience a more severe course of illness and poorer treatment outcome, due to a range of clinical and psychosocial factors that collectively impede remission and recovery. The aim of our paper is to review the role of pharmacotherapy in the treatment of comorbid BD-GD, in order to support clinical decisions according to the best available evidence., Methods: A qualitative systematic review of studies on pharmacological treatment in comorbid BD-GD was performed. A comprehensive literature search of online databases, bibliographies of published articles and gray literature was conducted. Data on efficacy, safety and tolerability were extracted and levels of evidence were assessed. We also provide a brief overview of current epidemiological, neurobiological and clinical findings, with the intention of proposing a dimensional approach to the choice of available drugs., Results: The only drug with a high level of evidence is lithium. Considering the inclusion of GD in DSM-5 'Substance-related and Addictive Disorders' category, we discuss the use of other drugs with a high level of evidence currently used in BD subjects with co-occurring substance use disorders., Limitations: Only few clinical trials are available and the population is limited; therefore no conclusive evidence can be inferred., Conclusions: Further randomized controlled trials are required to evaluate the efficacy of pharmacological treatment strategies in large samples of patients with comorbid BD-GD. Also, attempts should be made to identify other shared clinical and psychopathological domains that are amenable to treatment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background/aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes., Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment., Results: Depressed patients with and without anhedonia showed significantly lower (123)I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of (123)I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer., Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a 'state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state., (© 2015 S. Karger AG, Basel.)

Background: The aim of our study was to assess hedonic capacity in euthymic bipolar subjects, identifying possible differences compared to remitted unipolar depressed patients and healthy controls., Methods: 107 subjects with bipolar disorders, 86 with major depressive disorder and 106 healthy controls, homogeneous with respect to demographic characteristics, were enrolled. The following scales were administered: the Snaith-Hamilton pleasure scale (SHAPS), the subscale for 'anhedonia/asociality' of the scale for the assessment of negative symptoms (SANS) and the visual analogue scale (VAS) for hedonic capacity., Results: Scores on SHAPS total, interests and social interactions, SANS 'anhedonia/asociality' and VAS were all significantly higher in affective disorder patients compared to healthy controls. No difference was found between clinical groups. 20.5% (n=22) of bipolar disorder subjects and 24.5% (n=21) of major depressed subjects showed a significant reduction in hedonic capacity (SHAPS total score ≥ 3), compared to 7.5% (n=8) of healthy controls (χ(2)=12.03; p=.002)., Limitations: Limitations include heterogeneity with respect to pharmacological status and longitudinal course (i.e., 'single' vs. 'recurrent' affective episodes)., Conclusions: The major finding of our study is that euthymic bipolar patients and remitted major depressed patients display residual anhedonic symptoms. This suggests that, in affective disorder patients, altered hedonic capacity could represent an enduring trait and that, possibly, dysfunctions in the neurobiological mechanisms underlying hedonic response and reward processing persist, irrespective of mood state., (Copyright © 2012 Elsevier B.V. All rights reserved.)

It is now well established that major depression is accompanied and characterized by altered responses of the immune-inflammatory system. In this study we investigated the pro-inflammatory activation of monocytes isolated from depressed patients as a parameter not influenced by such confounds as the time of day, the nutritional and exercise status or the age and gender of patients. Monocytes from depressed patients and from healthy controls were isolated in vitro; after 24-h incubation under basal conditions, cells were exposed for 24-h to 100 ng/ml of endotoxin (bacterial lipopolysaccharide, LPS). We found that monocytes from drug-free depressed patients and controls release the same amounts of prostaglandin E2 (PGE2) under basal conditions, whereas monocytes from patients are dramatically less reactive to LPS (8.62-fold increase vs previous 24 hrs) compared to healthy controls (123.3-fold increase vs previous 24 hrs). Such blunted prostanoid production was paralleled by a reduction in COX-2 gene expression, whereas other pro-inflammatory mediators, namely interleukin-1β (IL-1 β) and -6 (IL-6) showed a trend to increased gene expression. The above changes were not associated to increased levels of circulating glucocorticoids. After 8 months of antidepressive drug treatment, the increase in PGE2 production after the endotoxin challenge was partially restored, whereas the increase in IL-1 β and -6 levels observed at baseline was completely abolished. In conclusion, our findings show that the reactivity of monocytes from depressed patients might be considered as a marker of the immune-inflammatory disorders associated to depression, although the lack of paired healthy controls at follow-up does not allow to conclude that monocyte reactivity to endotoxin is also a marker of treatment outcome.

Purpose: Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of (123)I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity., Methods: Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific (123)I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects., Results: As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and (123)I-FP-CIT uptake ratios in healthy subjects., Conclusion: We found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the inverse correlation was present in each group of patients, supporting the fascinating perspective that common subcortical substrates may be involved in both anxiety and depression dimensions and movement disorders.

The advent of the Internet is among the most significant changes in recent decades and has greatly affected the entire range of human experience. However, it has, in turn, led to the emergence of psychopathological features of addiction linked to its use. Literature on the clinical management of the distress related to Internet use systematically measures up to an evolving nosography, with ambiguous definitions of the phenomenon and a diversity of diagnostic, prognostic, and therapeutic criteria. To date, case studies on "Internet addiction" treatment are rather limited, and no standard clinical treatment protocols exist. With regard to pharmacological treatment options, empirical or anecdotal assessments are mostly referred to. The aim of this article was to review current literature on Internet addiction treatment and assess the extent to which specific pharmacological interventions alleviate these patients' symptomatic burden, to propose a rationale that may guide the therapeutic approach. To this end, we also explored pharmacological interventions that target patterns of comorbidity and underlying psychopathological dimensions shared with other behavioral or substance addictions.

Objectives: High, normal, or low plasma magnesium (Mg) levels have been observed in depressed patients. The aim of our study was to investigate the relationship of Mg levels with depression severity, specific psychopathological dimensions, and treatment outcome., Methods: A total of 123 outpatients during a major depressive episode were recruited. All patients showed at least two major depressive episodes and did not achieve remission in the former treatment trial. A blood sample was collected to determine total plasma Mg levels. The psychopathological status was assessed using Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression Retardation Rating Scale for psychomotor retardation, and Snaith-Hamilton Pleasure Scale for anhedonia. Hamilton Depression Rating Scale was repeated at 3 months after treatment., Results: All patients showed Mg levels mostly within the normal range. No association between Mg levels and psychopathological severity was reported. Patients who responded to antidepressant treatment showed higher Mg levels and higher retardation scores at basal evaluation in comparison with non-responders., Discussion: Although further studies investigating the relationship between hypomagnesaemia, depression, and treatment outcome are certainly necessary, we have hypothesized that hypomagnesaemia could be an epiphenomenic biochemical trait in less drug-responsive depressed patients. It is also plausible that lower Mg levels and hyperactive traits identify a biological subtype of patients with increased catecholaminergic functioning and a poorer response to aminergic drugs. Moreover, Mg depletion could partly account for the correlation between low Mg levels and poor outcome and this raises the question of Mg's possible therapeutic role in depression.

Numerous studies have been performed on magnesium (Mg) metabolism in patients with mood disorders but consistent results have not been obtained. To date, systematic clinical data about Mg levels in major depressed patients according to the psychopathological profile are not available. In the present study we have investigated the relationship between plasma Mg level severity of symptoms and specific psychopathological dimensions (anhedonia and retardation) in 53 mild-to-moderately depressed patients (M/F = 21/32; mean age 46.49 +/- 13.48). The psychopathological status was assessed using standard psychometric evaluation scales: HAM-D for severity of depression, HAM-A for severity of anxiety symptoms, DRRS for psychomotor retardation and SHAPS for anhedonia. We did not find any significant correlation between total plasma Mg levels (0.86 +/- 0.09 mmol/L), severity of depression (HAM-D = 17.13 +/- 6.76) and anxiety (HAM-A = 16.62 +/- 6.60). A statistically significant correlation between Mg levels and psychomotor retardation was observed. Patients with higher psychomotor retardation scores (DRRS = 20.41 +/- 7.72) showed higher plasma Mg levels (0.89 +/- 0.07 mmol/L), even though they remained in the normal range, in comparison to patients with lower retardation scores (DRRS = 7.29 +/- 3.80; Mg = 0.82 +/- 0.10 mmol/L). A relationship between catecholamines and Mg metabolism has been described and our results support the hypothesis that hypermagnesaemia might lead to hypoactivity and psychomotor retardation which is so often observed in depressed patients.

Central dopaminergic dysfunction has been widely proposed as a common neurobiological correlate of the psychopathological expression of anhedonia. The dopamine transporter (DAT) is a predominantly presynaptic receptor that may play a critical role in the pathophysiology of dopaminergic transmission. The aim of our study was to evaluate DAT binding in a population of depressed patients with anhedonia. Single photon emission computed tomography (SPECT) with the radiotracer DATSCAN was used to evaluate DAT binding in 11 depressed patients with anhedonia and 9 healthy comparison subjects. Compared with healthy subjects, patients showed significantly lower DAT binding. No significant correlation was found between DAT binding ratios and scores on administered psychometric tests. These findings suggest an alteration in DAT density in depressed patients with anhedonia that may be a primary susceptibility factor or a secondary phenomenon to reduced dopamine concentration in the synaptic cleft.

A case of 'dèlire de nègation' that suddenly appeared in a 43-year-old male is presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO-SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2) receptor binding that further decreased after treatment.