BOLD cardiorespiratory pulsatility in the brain: from noise to signal of interest.

Functional magnetic resonance imaging (fMRI) based on the Blood Oxygen Level Dependent (BOLD) contrast has been extensively used to map brain activity and connectivity in health and disease. Standard fMRI preprocessing includes different steps to remove confounds unrelated to neuronal activity. First, this narrative review explores how signal fluctuations due to cardiac and respiratory activity, usually considered as "physiological noise" and regressed out from fMRI time series. However, these signal components bear useful information about some mechanisms of brain functioning (e.g., glymphatic clearance) or cerebrovascular compliance in response to arterial pressure waves. Aging and chronic diseases can cause stiffening of the aorta and other main arteries, with a reduced dampening effect resulting in greater transmission of pressure impulses to the brain. Importantly, the continuous hammering of cardiac pulsations can produce local alterations of the mechanical properties of the small cerebral vessels, with a progressive deterioration that ultimately affects neuronal functionality. Second, the review emphasizes how fMRI can study the brain patterns most affected by cardiac pulsations in health and disease with high spatiotemporal resolution, offering the opportunity to identify much more specific risk markers than systemic factors based on measurements of the vascular compliance of large arteries or other global risk factors. In this regard, modern fast fMRI acquisition techniques allow a better characterization of these pulsatile signal components due to reduced aliasing effects, turning what has been traditionally considered as noise in a signal of interest that can be used to develop novel non-invasive biomarkers in different clinical contexts.

COVID-19 and first manic episodes: a systematic review.

Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the occurrence of several neurological syndromes during and after COVID-19. Growing evidence indicates that Sars-CoV-2 can also trigger the acute onset of mood disorders or psychotic symptoms. COVID-19-related first episodes of mania, in subjects with no known history of bipolar disorder, have never been systematically analyzed. Thus, the present study assesses a potential link between the two conditions. This systematic review analyzes cases of first appearance of manic episodes associated with COVID-19. Clinical features, pharmacological therapies, and relationships with pre-existing medical conditions are also appraised. Medical records of twenty-three patients fulfilling the current DSM-5 criteria for manic episode were included. Manic episodes started, on average, after 12.71±6.65 days from the infection onset. Psychotic symptoms were frequently reported. 82.61% of patients exhibited delusions, whereas 39.13% of patients presented hallucinations. A large discrepancy in the diagnostic workups was observed. Mania represents an underestimated clinical presentation of COVID-19. Further studies should focus on the pathophysiological substrates of COVID-19-related mania and pursue appropriate and specific diagnostic and therapeutic workups.

Characterizing the building blocks of Problematic Use of the Internet (PUI): The role of obsessional impulses and impulsivity traits among Italian young adults.

BACKGROUND: Problematic Use of the Internet (PUI) is a considerable issue of the modern era, but its risk factors are still poorly understood. Impulsivity and obsessive-compulsive symptoms have been associated with PUI, but this relationship is still debated. In this article we focus on the relationships of PUI with obsessive-compulsive and impulsive symptoms in a cohort of Italian young adults, in order to identify possible vulnerability factors for PUI. METHODS: A sample of 772 Italian individuals aged 18-30 (mean age 23.3 ± 3.3 years old; 38% males and 62% females) was assessed via online survey using the Internet Addiction Test (IAT), the Mini International Neuropsychiatric Interview (MINI) Screen, the Padua Inventory-Washington State University Revision (PI-WSUR) and the Barratt Impulsiveness Scale (BIS-11). RESULTS: Ninety-seven subjects (12.6% of the sample) reported IAT scores at risk for PUI. PUI participants reported higher levels of impulsivity, obsessive-compulsive symptoms and a higher burden of co-occurrent psychiatric symptoms. In a logistic regression model, obsessional impulses to harm (OR = 1.108, p < 0.001), attentional impulsivity (OR = 1.155, p < 0.001) and depressive symptomatology (OR = 1.246, p = 0.012) had significant association with PUI. Finally, higher severity of PUI has been associated with manic/psychotic symptoms and with attentional impulsivity. CONCLUSIONS: Our findings confirmed the role of impulsivity in PUI, while also underling the association of obsessional impulses with this pathological behavior. We could hypothesize a trigger role of obsessive impulses for the engagement in PUI, together with factors as negative affective states. Further research is needed with respect to more severe forms of PUI, also for establishing tailored interventions.

Osteopathy modulates brain-heart interaction in chronic pain patients: an ASL study.

In this study we used a combination of measures including regional cerebral blood flow (rCBF) and heart rate variability (HRV) to investigate brain-heart correlates of longitudinal baseline changes of chronic low back pain (cLBP) after osteopathic manipulative treatment (OMT). Thirty-two right-handed patients were randomised and divided into 4 weekly session of OMT (N = 16) or Sham (N = 16). Participants aged 42.3 ± 7.3 (M/F: 20/12) with cLBP (duration: 14.6 ± 8.0 m). At the end of the study, patients receiving OMT showed decreased baseline rCBF within several regions belonging to the pain matrix (left posterior insula, left anterior cingulate cortex, left thalamus), sensory regions (left superior parietal lobe), middle frontal lobe and left cuneus. Conversely, rCBF was increased in right anterior insula, bilateral striatum, left posterior cingulate cortex, right prefrontal cortex, left cerebellum and right ventroposterior lateral thalamus in the OMT group as compared with Sham. OMT showed a statistically significant negative correlation between baseline High Frequency HRV changes and rCBF changes at T2 in the left posterior insula and bilateral lentiform nucleus. The same brain regions showed a positive correlation between rCBF changes and Low Frequency HRV baseline changes at T2. These findings suggest that OMT can play a significant role in regulating brain-heart interaction mechanisms.

Effect of manual approaches with osteopathic modality on brain correlates of interoception: an fMRI study.

The present randomised placebo controlled trial explored the extent to which osteopathic manipulative treatment (OMT) affects brain activity, particularly the insula, during both an "interoceptive awareness" and "exteroceptive awareness" task in a sample of 32 right-handed adults with chronic Low Back Pain (CLBP) randomly assigned to either the OMT or sham group. Patients received 4 weekly sessions and fMRI was performed at enrolment (T0), immediately after the first session (T1) and at 1 month (T2). The results revealed that the OMT produced a distinct and specific reduction in BOLD response in specific brain areas related to interoception, i.e., bilateral insula, ACC, left striatum and rMFG. The observed trend across the three time points appears uncharacteristic. At T1, a marginal increase of the BOLD response was observed in all the above-mentioned areas except the rMFG, which showed a decrease in BOLD response. At T2, the response was the opposite: areas related to interoception (bilateral insula and ACC) as well as the rMFG and left striatum demonstrated significant decreased in BOLD response. The findings of this study provide an insight into the effects of manual therapies on brain activity and have implications for future research in the field.

Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements.

OBJECTIVES: Variants appearing de novo in genes regulating key neurodevelopmental processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may increase the risk for schizophrenia. However, CREs involvement in schizophrenia needs to be explored more deeply. METHODS: We investigated de novo copy-number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands by using the Enhancer Chip, a customised array CGH able to investigate the whole genome with a 300-kb resolution, specific disease loci at a ten-fold higher resolution, and which was highly enriched in probes in more than 1,250 enhancer elements selected from Vista Enhancer Browser. RESULTS: In seven patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements. De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain development, while that involving the enhancer element hs1043, also includes ZIC1, which plays a role in neural development and is responsible of behavioural abnormalities in Zic mutant mice. CONCLUSIONS: These findings provide further evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia and suggest that CNVs affecting regulatory enhancer elements could contribute to the genetic vulnerability to the disorder.

Effect of Continuous Touch on Brain Functional Connectivity Is Modified by the Operator's Tactile Attention.

Touch has been always regarded as a powerful communication channel playing a key role in governing our emotional wellbeing and possibly perception of self. Several studies demonstrated that the stimulation of C-tactile afferent fibers, essential neuroanatomical elements of affective touch, activates specific brain areas and the activation pattern is influenced by subject's attention. However, no research has investigated how the cognitive status of who is administering the touch produces changes in brain functional connectivity of touched subjects. In this functional magnetic resonance imaging (fMRI) study, we investigated brain connectivity while subjects were receiving a static touch by an operator engaged in either a tactile attention or auditory attention task. This randomized-controlled single-blinded study enrolled 40 healthy right-handed adults and randomly assigned to either the operator tactile attention (OTA) or the operator auditory attention (OAA) group. During the five fMRI resting-state runs, the touch was delivered while the operator focused his attention either: (i) on the tactile perception from his hands (OTA group); or (ii) on a repeated auditory stimulus (OAA group). Functional connectivity analysis revealed that prolonged sustained static touch applied by an operator engaged with focused tactile attention produced a significant increase of anticorrelation between posterior cingulate cortex (PCC-seed) and right insula (INS) as well as right inferior-frontal gyrus but these functional connectivity changes are markedly different only after 15 min of touching across the OTA and OAA conditions. Interestingly, data also showed anticorrelation between PCC and left INS with a distinct pattern over time. Indeed, the PCC-left INS anticorrelation is showed to start and end earlier compared to that of PCC-right INS. Taken together, the results of this study showed that if a particular cognitive status of the operator is sustained over time, it is able to elicit significant effects on the subjects' functional connectivity patterns involving cortical areas processing the interoceptive and attentional value of touch.

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials.

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons.

The bridge between two worlds: psychoanalysis and fMRI.

In recent years, a connection between psychoanalysis and neuroscience has been sought. The meeting point between these two branches is represented by neuropsychoanalysis. The goal of the relationship between psychoanalysis and neuroscience is to test psychoanalytic hypotheses in the human brain, using a scientific method. A literature search was conducted on May 2015. PubMed and Scopus databases were used to find studies for the inclusion in the systematic review. Common results of the studies investigated are represented by a reduction, a modulation, or a normalization of the activation patterns found after the psychoanalytic therapy. New findings in the possible and useful relationship between psychoanalysis and neuroscience could change the modalities of relating to patients for psychoanalysts and the way in which neuroscientists plan their research. Researchers should keep in mind that in any scientific research that has to do with people, neuroscience and a scientific method cannot avoid subjective interpretation.

BDNF concentration and impulsiveness level in post-traumatic stress disorder.

Among the symptoms of post-traumatic stress disorder (PTSD), impulsiveness has been observed in patients with high levels of hyperarousal. Recent literature reveals the importance of investigating the role of neurotrophins, such as brain-derived neurotrophic factor (BDNF), in several psychiatric disorders. Specifically, contrasting findings have been reported on the levels of serum BDNF in subjects with PTSD. The aim of the present study was to investigate the correlation between BDNF serum levels and impulsiveness in PTSD. To this end, we measured BDNF serum levels in 23 PTSD patients and a control group of 19 trauma-exposed non-PTSD subjects. Results indicate a positive correlation in the PTSD group; that is, the higher the BDNF levels the higher the impulsiveness score, as measured by the Barratt Impulsiveness Scale (BIS-11), suggesting that impulsiveness could be associated with greater BDNF production. Alternatively, it is also possible that high impulsiveness acts as a psychological mechanism that counteracts the negative effects exerted by the traumatic experience and the associated obsessive thoughts. The present paper discusses both hypotheses.

Neural correlates of negative emotion processing in bipolar disorder.

INTRODUCTION: Bipolar disorder type I (BD-I) is characterized by a severe impairment in emotional processing during both acute and euthymic phases of the illness. The aim of the present study was to investigate negative emotion processing in both euthymic patients and non-affected first-degree relatives, looking for state and trait markers of BD-I. METHODS: 22 healthy relatives of BD-I patients (mean age 31.5±7.3 years; 15 females), 23 euthymic BD-I patients (mean age 35.2±7.9 years; 14 females), and 24 matched controls (mean age 32.5±6.2 years; 16 females) performed an IAPS-based emotional task during 1.5T fMRI. They were required to identify vegetable items (targets) inside neutral or negative pictures. RESULTS: Euthymic BD-I patients showed a significant reduced accuracy in target detection during both neutral and negative images presentation, whereas first-degree relatives performed similarly to normal comparisons. We found a reduced activation of Left precuneus during negative images condition in the patients only. By contrast, both patients and relatives hyperactivated the Left insula and hypoactivated the Right supramarginal gyrus with respect to controls. Moreover, relatives showed an increased activation of Right lingual gyrus and lower activation of pre-supplementary motor area and Right superior frontal gyrus. CONCLUSIONS: During a negative emotion task, euthymic BD-I patients and non-affected first-degree relatives shared an abnormal activation of a limbic area (Left insula) coupled with a reduced activation of a parietal region (Right supramarginal gyrus), thus suggesting a trait-like anomalous processing of affective contents. On the other hand, functional abnormalities found only in unaffected relatives and not in patients and controls may correspond to resilience factors.

Sustained attention in psychosis: Neuroimaging findings.

To provide a systematic review of scientific literature on functional magnetic resonance imaging (fMRI) studies on sustained attention in psychosis. We searched PubMed to identify fMRI studies pertaining sustained attention in both affective and non-affective psychosis. Only studies conducted on adult patients using a sustained attention task during fMRI scanning were included in the final review. The search was conducted on September 10(th), 2013. 15 fMRI studies met our inclusion criteria: 12 studies were focused on Schizophrenia and 3 on Bipolar Disorder Type I (BDI). Only half of the Schizophrenia studies and two of the BDI studies reported behavioral abnormalities, but all of them evidenced significant functional differences in brain regions related to the sustained attention system. Altered functioning of the insula was found in both Schizophrenia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlighting differences and similarities between Schizophrenia and BDI.

Amantadine and cognitive flexibility: decision making in Parkinson's patients with severe pathological gambling and other impulse control disorders.

INTRODUCTION: Dopamine replacement therapy for Parkinson's disease (PD) was recently linked to the development of impulse control disorders such as pathological gambling (PG), hypersexuality, compulsive shopping, and binge or compulsive eating. Antiglutamatergic agents including amantadine (Ama) reduce these behaviors in PD and non-PD patients. The aim of our study is to evaluate the changes in executive functions, emotions, and reward/loss processing during Ama treatment in PD patients. METHODS: Thirty-three patients affected by idiopathic PD were selected from a cohort of 1,096 PD patients and categorized in three different groups: ten affected by PG (PD-PG); nine PD patients with other impulse control disorder (PD-ICD); and 14 PD patient without any psychiatric disorder (PD-CTR-controls). For the neuropsychological evaluation, the following behavioral tasks where administered: the Stroop, the emotional Stroop, and the monetary reward/loss risk-taking tasks. RESULTS: During Ama treatment, PD-PGs showed a decrease in risky choices and an increase in non-risky choices (t(9)=-2.40, P<0.05 and t(9)=2,67, P<0.05 uncorrected, respectively). Between-group comparison showed a significant decrease in risky choices for PD-PG with respect to PD-CTR (t(22)=-4.16, P<0.01), and a decreased accuracy for positive words in comparison between PD-PG and PD-ICD (t(17)=-7,49, P<0.01) and PD-PG and PD-CTR (t(22)=-4.29, P<0.01). No within- and between-group differences were observed for Stroop task. DISCUSSION: Our data showed that Ama add-on therapy reduces hypersensitivity to reward and sustains activation toward uncertainty in PD-PG patients. These finding might explain the behavioral mechanism underlying the effect of antiglutamatergic drugs.

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

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

Prevalence of self-reported childhood abuse in psychosis: a meta-analysis of retrospective studies.

There is extensive clinical literature reporting traumatic childhood experiences in patients with psychosis. A quantitative meta-analysis addressing the prevalence of self-reported childhood sexual (CSA), physical (CPA) and emotional abuse (CEA) in psychotic patients has yet to be done. We conducted, a systematic literature search to identify retrospective studies addressing self-reported childhood abuse in patients with DSM/ICD psychosis. Demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors. Quantitative meta-analysis of CSA, CPA, CEA in the sample of patients was performed. Statistical heterogeneity and publication bias were assessed and meta-regressions performed to control for different moderators. Twenty-three studies were retrieved and included a total of 2017 psychotic patients. The prevalence of self-reported CSA, CPA, CEA were respectively of 26%, 39% and 34%. Age, publication year, gender and substance abuse moderated CSA, while age, clinical setting and substance abuse moderated CPA. Results indicated that CEA was moderated by gender and publication year of the study. According to our meta-analysis, psychotic patients have a consistently high self-report of childhood traumatic events which are sexual, physical and emotional in nature. It is our opinion that clinicians should be trained and skilled to carefully investigate childhood abuse in psychosis.

Lamotrigine augmentation in premenstrual dysphoric disorder: a case report.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome, characterized by depressive, anxious, and somatic symptoms, associated to a significant reduction in social functioning and quality of life. Although selective serotonin reuptake inhibitors (SSRIs) and oral contraceptives show a substantial effectiveness in PMDD, a wide percentage of women affected by PMDD do not respond to those first-line treatments. We present the case of a 42-year-old woman, affected by a disabling form of PMDD, who partially responded to an SSRI treatment and significantly improved after an add-on therapy with lamotrigine. We therefore suggest that lamotrigine may be an efficacious and safe augmentation strategy in severe PMDD cases showing unsatisfactory or partial response to SSRI treatments.

Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study.

OBJECTIVE: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD-I) and also in non-affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD-I patients and non-affected relatives during a sustained attention task. METHODS: Twenty-four euthymic BD-I patients, 22 non-affected first-degree relatives of BD-I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event-related fMRI scanning. RESULTS: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between-group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule - limited to the higher attention load - and an augmented deactivation of the posterior cingulate/retrosplenial cortex. CONCLUSIONS: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD-I patients and non-affected first-degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD-I.

Macrostructural alterations of subcortical grey matter in psychogenic erectile dysfunction.

Psychogenic erectile dysfunction (ED) has been defined as the persistent inability to attain and maintain an erection sufficient to permit sexual performance. It shows a high incidence and prevalence among men, with a significant impact on the quality of life. Few neuroimaging studies have investigated the cerebral basis of erectile dysfunctions observing the role played by prefrontal, cingulate, and parietal cortices during erotic stimulation. In spite of the well-known involvement of subcortical regions such as hypothalamus and caudate nucleus in male sexual response, and the key role of nucleus accumbens in pleasure and reward, poor attention was paid to their role in male sexual dysfunction. In this study, we determined the presence of grey matter (GM) atrophy patterns in subcortical structures such as amygdala, hippocampus, nucleus accumbens, caudate nucleus, putamen, pallidum, thalamus, and hypothalamus in patients with psychogenic ED and healthy men. After Rigiscan evaluation, urological, general medical, metabolic and hormonal, psychological and psychiatric assessment, 17 outpatients with psychogenic ED and 25 healthy controls were recruited for structural MRI session. Significant GM atrophy of nucleus accumbens was observed bilaterally in patients with respect to controls. Shape analysis showed that this atrophy was located in the left medial-anterior and posterior portion of accumbens. Left nucleus accumbens volumes in patients correlated with low erectile functioning as measured by IIEF-5 (International Index of Erectile Function). In addition, a GM atrophy of left hypothalamus was also observed. Our results suggest that atrophy of nucleus accumbens plays an important role in psychogenic erectile dysfunction. We believe that this change can influence the motivation-related component of sexual behavior. Our findings help to elucidate a neural basis of psychogenic erectile dysfunction.

Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study.

The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy.Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively.Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores.In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.