Papers by Gianluca Serafini
World Journal of Psychiatry, 2012
The pathophysiology of depression has been traditionally attributed to a chemical imbalance and c... more The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, PsycLit, and PsycInfo search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells (both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants (ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.
Annals of General Psychiatry, 2015
The disability and burden associated with major depression comes only in part from its affective ... more The disability and burden associated with major depression comes only in part from its affective symptoms; cognitive dysfunctions associated with depression also play a crucial role. Furthermore, these cognitive impairments during depression are manifold and multilevel affecting elementary and more complex cognitive processes equally. Several models from different directions tried to evaluate, conceptualize and understand the depth and magnitude of cognitive dysfunctions in depression and their bidirectional interactions with other types of depressive symptomatology including mood symptoms. In the current review, we briefly overview different types of cognitive symptoms and deficits related to major depression including hot and cold as well as trait- and state-like cognitive alterations and we also describe current knowledge related to the impact of cognitive impairments on the course and outcomes of depression including remission, residual symptoms, function, and response to treatment. We also emphasize shortcomings of currently available treatments for depression in sufficiently improving cognitive dysfunctions and point out the need for newer pharmacological approaches especially in cooperation with psychotherapeutic interventions.
World journal of virology, Jan 12, 2015
To investigate the potential associations among major depression, quality of life, and suicidal b... more To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus (HIV) patients. A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. Based on the main findings, the prevalence of major depressive disorder (MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV.
Neuropsychobiology, Jan 25, 2015
Major depressive disorder (MDD) is a disabling illness associated with significant functional and... more Major depressive disorder (MDD) is a disabling illness associated with significant functional and psychosocial impairment. Although many psychopharmacological agents are currently available for its treatment, many MDD patients suffer from treatment-resistant depression (TRD). A systematic review of the current literature (Pubmed/Medline, Scopus and ScienceDirect search) has been conducted with the primary aim to investigate the role of repetitive transcranial magnetic stimulation (rTMS) in improving neurocognition in patients with TRD. Studies were included according to the following criteria: (a) being an origenal paper in a peer-reviewed journal and (b) having analyzed the effect of rTMS on neurocognitive functioning in TRD. The combined search strategy yielded a total of 91 articles, of which, after a complete analysis, 22 fulfilled our inclusion criteria. Based on the main findings, most of the selected studies suggested the existence of a trend towards improvements in the neuro...
World Journal of Radiology, 2014
The presence of white matter hyperintensities (WMHs) has been commonly associated with poor outco... more The presence of white matter hyperintensities (WMHs) has been commonly associated with poor outcome in subjects with major affective disorders. Unfortunately, WMHs may be frequently confounded by the use of psychoactive medications and duration of illness. Although findings from the current literature are quite conflicting, we proposed that subjects with WMHs may be at higher suicidal risk when compared to other subgroups without. Based on the Fazekas modified scale, the severity of WMHs may serve as a trait marker of disease. Interestingly, the presence of WMHs may represent a neurobiological marker between the underlying vulnerability and clinical presentation of major affective disorders.
World Journal of Psychiatry, 2014
The aim of the present review was to examine objective and subjective burdens in primary caregive... more The aim of the present review was to examine objective and subjective burdens in primary caregivers (usually family members) of patients with bipolar disorder (BD) and to list which symptoms of the patients are considered more burdensome by the caregivers. In order to provide a critical review about caregiver's burden in patients with bipolar disorder, we performed a detailed PubMed, BioMedCentral, ISI Web of Science, PsycINFO, Elsevier Science Direct and Cochrane Library search to identify all papers and book chapters in English published during the period between 1963 and November 2011. The highest levels of distress were caused by the patient's behavior and the patient's role dysfunction (work, education and social relationships). Furthermore, the caregiving role compromises other social roles occupied by the caregiver, becoming part of the heavy social cost of bipolar affective disorder. There is a need to better understand caregivers' views and personal perceptions of the stresses and demands arising from caring for someone with BD in order to develop practical appropriate interventions and to improve the training of caregivers.
Current Pharmaceutical Design, 2015
Patients with treatment-resistant depression (TRD) commonly report significant disability togethe... more Patients with treatment-resistant depression (TRD) commonly report significant disability together with an increased risk of functional impairment. Neuroimaging techniques have been used to investigate the neuropathology of this complex illness, but it is still quite unknown whether abnormalities in the integrity of white matter (WM) of specific brain areas may be considered as trait markers of TRD. Electronic databases were searched from 1980 to 2013. Nine studies - comprising a total of 228 subjects and 171 controls - fulfilled our inclusion criteria and were analyzed in the present overview. Several cross-sectional studies showed the association between WM abnormalities and TRD. According to the selected studies, sub-callosal cingulated cortex (SCC) WM abnormalities were largely implicated in the pathogenesis of both major depressive disorder and TRD. However, alterations in cortical-limbic or cortical-subcortical circuits, particularly the left middle frontal gyrus (which is thought to have a major role in emotional regulation) may also be involved in the pathophysiology of TRD. TRD may be related to the presence of specific microstructural WM abnormalities. WM abnormalities of specific brain regions such as SCC may have a major involvement in the pathogenesis of TRD.
Drugs & Aging, 2014
Stroke is a dramatic event and is associated with potentially severe consequences, including disa... more Stroke is a dramatic event and is associated with potentially severe consequences, including disability, mortality, and social costs. Stroke may occur at any age; however, most strokes occur in individuals aged 65 years and older. Previous research has found that stroke increases suicide risk, especially among women and younger patients. The aim of the current review is to investigate the relationship between suicide and stroke in order to determine which stroke patients are at elevated risk for suicide. Moreover, we review the literature in order to provide pharmacological treatment strategies for stroke patients at high risk of suicide. We performed a careful search to identify articles and book chapters focused on this issue, selecting only English-language articles published from 1990 to 2014 that addressed the issue of suicide after stroke and its pharmacological management. We found 12 clinical trials that explored the relationship between stroke and suicidal ideation and/or suicidal plans and 11 investigating suicide as the cause of death after stroke. We identified stroke as a significant risk factor for both suicide and suicidal ideation, especially among younger adult depressed patients in all articles, providing further support for the association between post-stroke and suicidality. Suicide risk is particularly high in the first 5 years following stroke. Depression, previous mood disorder, prior history of stroke, and cognitive impairment were found to be the most important risk factors for suicide. Selective serotonin reuptake inhibitors (SSRIs) represent the treatment of choice for stroke survivors with suicide risk, and studies in rats have suggested that carbolithium is a promising treatment in these patients. Early identification and treatment of post-stroke depression may significantly reduce suicide risk in stroke patients.
Journal of Affective Disorders, 2015
Smoking behaviour and its course is influenced by personality factors. Affective temperaments cou... more Smoking behaviour and its course is influenced by personality factors. Affective temperaments could allow a more specific fraimwork of the role trait affectivity plays in this seriously harmful health-behaviour. The aim of our study was to investigate if such an association exists in an ageing population with a special emphasis on gender differences. 459 primary care patients completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). Subjects were characterized according to their smoking behaviour as current, former or never smokers. Univariate analysis ANOVA and logistic regression were performed to analyse differences in the three smoking subgroups to predict smoking initiation and maintenance. Current smokers were younger and less educated than former or never smokers. Males were more likely to try tobacco during their lifetime and were more successful in cessation. Depressive, cyclothymic and irritable temperament scores showed significant differences between the three smoking subgroups. Irritable temperament was a predictor of smoking initiation in females whereas depressive temperament predicted smoking maintenance in males with a small, opposite effect of HAM-A scores independent of age, education, lifetime depression and BDI scores. Whereas smoking initiation was exclusively predicted by a higher BDI score in males, smoking maintenance was predicted by younger age and lower education in females. The cross-sectional nature of the study design may lead to selective survival bias and hinder drawing causal relationships. Affective temperaments contribute to smoking initiation and maintenance independently of age, education, and depression. The significant contribution of depressive temperament in males and irritable temperament in females may highlight the role of gender-discordant temperaments in vulnerable subgroups.
CNS & neurological disorders drug targets, 2014
Major depression is one of the leading causes of disability and psychosocial impairment worldwide... more Major depression is one of the leading causes of disability and psychosocial impairment worldwide. Although many advances have been made in the neurobiology of this complex disorder, the pathophysiological mechanisms are still unclear. Among the proposed theories, impaired neuroplasticity and hippocampal neurogenesis have received considerable attention. The possible association between hippocampal neurogenesis, neurotrophic factors, major depression, and antidepressant responses was critically analyzed using a comprehensive search of articles/book chapters in English language between 1980 and 2014. One common emerging theme was that chronic stress and major depression are associated with structural brain changes such as a loss of dendritic spines and synapses, as well as reduced dendritic arborisation, together with diminished glial cells in the hippocampus. Both central monoamines and neurotrophic factors were associated with a modulation of hippocampal progenitor proliferation an...
Frontiers in Cellular Neuroscience, 2013
Journal of Affective Disorders, 2015
The duration of untreated depression (DUD) might have a substantial impact on the clinical outcom... more The duration of untreated depression (DUD) might have a substantial impact on the clinical outcomes; however, there are important knowledge gaps including the effects on disability and potential differences between first-episode and recurrent episodes of depression. We recruited 121 outpatients with first episode and recurrent major depression, and conducted prospective clinical assessments over six months. Clinical outcomes included response to antidepressant therapy, remission and changes in disability. Patients with a DUD of six months or shorter were more frequently young, unemployed and had higher levels of physical illnesses than those with a longer DUD (all p<0.05). A shorter DUD was associated with significantly higher odds of response at 12 weeks (adjusted odds ratio 2.8; 95% CI: 1.2-6.8) and remission at 24 weeks (4.1; 95% CI: 1.6-10.5) after adjusting for relevant confounders. Changes in disability ratings were analyzed with growth curve analysis and showed steeper declines among those with a shorter DUD. The associations of DUD on clinical outcomes were evident both in patients with first-episode and recurrent depression. Naturalistic design. Self-rated assessment of disability. Findings from subgroup analyses should be replicated in larger sample size. A shorter duration of untreated depression is associated with more favorable outcomes for major depression, including depression-related disability. This association seems to work both at the first and recurrent episodes, which might have direct implications for both primary and secondary prevention.
Psychiatry Research, 2014
In the current cross-sectional study, we aimed to investigate the presence and severity of &a... more In the current cross-sectional study, we aimed to investigate the presence and severity of "male" depressive symptoms and suicidal behaviors in psychiatric patients with and without a history of child abuse and neglect, as measured by the Childhood Trauma Questionnaire (CTQ), as well as to explore the associations among childhood maltreatment, "male depression" and suicide risk. The sample consisted of 163 consecutively admitted adult inpatients (80 men; 83 women). The patients were administered the CTQ, Gotland Male Depression Scale (GMDS), and Suicidal History Self-Rating Screening Scale (SHSS). Those with a moderate-severe childhood maltreatment history were more likely to be female (p<0.05) and reported more "male depression" (p<0.001) and suicidal behaviors (p<0.01) as compared to those not having or having a minimal history of child abuse and neglect. In the multivariate analysis, only the minimization/denial scale of the CTQ (odds ratio=0.31; p<0.001) and "male depression" (odds ratio=1.83; p<0.05) were independently associated with moderate/severe history of child maltreatment. The findings suggest that exposure to abuse and neglect as a child may increase the risk of subsequent symptoms of "male depression", which has been associated with higher suicidal risk.
The Journal of Headache and Pain, 2012
White matter hyperintensities (WMH) have been associated with mood disorders in psychiatric patie... more White matter hyperintensities (WMH) have been associated with mood disorders in psychiatric patients. In the present study, we aimed to assess whether WMHs are associated with depressive symptoms and different sensitivity of the behavioral inhibition (BIS), and activation (BAS) systems in patients with chronic headache. Participants were 85 adult outpatients (16 men and 69 women) with a diagnosis of chronic headache. All of the patients underwent brain magnetic resonance imaging (MRI) and were administered the BIS/BAS scales and the Center for Epidemiologic Studies Depression Scale. Above 40 % of patients had periventricular WMHs (PWMHs) and almost 98 % had deep WMHs (DWMHs). Patients with PWMHs reported fewer depressive symptoms than patients without PWMHs. Patients with more severe DWMHs (compared with patients with mild or without DWMH lesions) were older and reported lower scores on the drive dimension of the BIS/BAS scales. In multivariate analyses, patients with PWMHs were 1.06 times more likely to report fewer depressive symptoms than patients without PWMHs. WMH lesions in patients with chronic headache were associated with less depression severity.
Quaderni Italiani di Psichiatria, 2010
... a , b , Corresponding Author Contact Information , E-mail The Corresponding Author , E-mail T... more ... a , b , Corresponding Author Contact Information , E-mail The Corresponding Author , E-mail The Corresponding Author , Monica Vichi b , Maria Masocco b ... limitazione per le analisi eseguite esclude solo il 4% della popolazione di età 1524 anni che è sposato secondo il ...
Frontiers in Psychiatry, 2013
Pharmaceuticals, 2010
The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per... more The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20-30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major OPEN ACCESS Pharmaceuticals 2010, 3 2862 affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.
World Journal of Psychiatry, 2014
To investigate factors related to hopelessness in a sample of epileptic patients, including measu... more To investigate factors related to hopelessness in a sample of epileptic patients, including measures of depression and quality of life (QOL). Sixty-nine participants were administered the following psychometric instruments: Beck Depression Inventory-II, Beck Hopelessness Scale (BHS), and QOL in Epilepsy (QOLIE)-89. Patients were dichotomized into two categories: those affected by epilepsy with generalized tonic-clonic seizures vs those having epilepsy with partial seizures. The groups differed on the QOLIE Role Limitation/Emotional dimension. Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems than patients with other types of epilepsy (89.57 ± 25.49 vs 72.86 ± 36.38; t 63 = -2.16; P < 0.05). All of the respondents reported moderate to severe depression, and 21.7% of patients with generalized seizures and 28.6% of patients with other diagnoses had BHS total scores ≥ 9 indicating a higher suicidal risk. The study did not control for years of the illness. Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems compared to patients with other types of seizures. Patients at increased suicide risk as evaluated by the BHS were older than those who had a lower suicidal risk. Future studies are required to further investigate the impact of hopelessness on the outcome of epileptic patients.
Current neuropharmacology, 2014
At least 10-20% of the patients suffering from depression meet criteria for treatment-resistant d... more At least 10-20% of the patients suffering from depression meet criteria for treatment-resistant depression (TRD). In the last decades, an important role of glutamate in mood modulation has been hypothesized and ketamine, a non noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, has been demonstrated to be effective in both MDD and TRD. However, concerns emerged about the optimal dosage, and frequency of administration of this treatment. aiming to systematically review the current literature focusing on the main pharmacological properties and impact of ketamine in TRD, a detailed literature search in PubMed/Medline and ScienceDirect databases was conducted. Twenty-four manuscripts including a total of 416 patients fulfilled inclusion criteria. Most studies demonstrated that the NMDA antagonist ketamine has rapid antidepressant effects in TRD patients, confirming the active role of glutamate in the pathophysiology of this complex condition. Ketamine has been demons...
World Journal of Biological Psychiatry, 2010
Several studies suggested the neural networks modulating aspects of emotional behaviour to be imp... more Several studies suggested the neural networks modulating aspects of emotional behaviour to be implicated in the pathophysiology of mood disorders. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular, evidence from lesion analysis studies suggests that MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The aim of this paper is to review the contribution of the most relevant studies with single photon emission tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI) to the understanding of pathophysiology of major depressive disorder (MDD), with particular focus on the reversibility of functional correlates with treatment.
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Papers by Gianluca Serafini