ADHD and eating disorders in childhood and adolescence: An updated minireview.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. However, little is still known about the association between ADHD and EDs through childhood and adolescence. Therefore, in the present work, we aimed at summarizing the studies investigating ADHD and EDs in childhood and adolescence over the last 10 years. METHODS: A bibliographic search on PubMed was performed and only studies that considered participants with a clinical diagnosis of ADHD, patients with an additional diagnosis of EDs and patients under 18 years old were included. A total of 7 studies were retrieved and included in the review. RESULTS: The majority of the reviewed studies (N = 5) found an association between ADHD and EDs, while the remaining, which focused on EDs symptomatology, reported either lower ED symptoms in ADHD sample or no association between ADHD and EDs. LIMITATIONS: the majority of studies were cross-sectional and therefore did not allow to explore the longitudinal casual relation between ADHD and EDs in the developmental age range considered. CONCLUSIONS: This review suggests that children and adolescents with ADHD should be monitored for EDs. However, more work is still needed to better understand the clinical implications of the comorbidity between ADHD and EDs and its prospective impact on the life of children and adolescents with ADHD.

Imaging associations of self-injurious behaviours amongst patients with Borderline Personality Disorder: A mini-review.

BACKGROUND: Borderline Personality Disorder (BPD) is a severe and disabling psychiatric syndrome, frequently associated with self-injurious behaviours (SIB). In recent years, functional magnetic resonance imaging (fMRI) investigations have tried to identify alterations associated with SIB amongst BPD patients, in order to better delineate possible neurobiological underpinnings of these manifestations. In this mini-review, we aimed at summarizing fMRI studies exploring patterns of neural activation associated with SIB in BPD patients. METHODS: Literature searches on PubMed, Psych-Info and Embase databases were performed for all fMRI studies including adult patients with BPD and SIB undergoing different tasks, including painful or thermic stimulation, affective stimulation through the presentation of picturesor the recollection of personal memories as well as tasks that evaluate sustained attention and impulsivity, and reward processing. Thirteen relevant papers were considered eligible for the present review. RESULTS: Patients with BPD and SIB, compared to HC, showed prefrontal, nucleus accumbens overactivation and amygdala deactivation during pain stimulation. During negative affective stimulation, BPD patients showed a hyperactivation of the amygdala and a hypoactivation of the orbitofrontal cortex (OFC), which was also found to be enhanced during a gambling task and during a recalling of aversive memories. In contrast, during cognitive tasks with negative affective interference, BPD patients showed hypoactivation of OFC, anterior cingulated cortex, and basal ganglia. LIMITATIONS: The limited number of studies and the heterogeneity regarding the fMRI tasks employed allowed only suggestive conclusions. CONCLUSIONS: The reviewed fMRI studies highlighted that BPD patients with a history of SIB showed altered brain activity, compared to HC, in regions involved in inhibitory cognitive processes and affect regulation, which may in turn, explain the overwhelming emotional experiences eliciting SIB in these patients.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Olfactory and gustatory dysfunctions in SARS-CoV-2 infection: A systematic review.

BACKGROUND: Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: A systematic review comprising all the observational studies that reported the prevalence and/or the longitudinal trajectories of OGD in COVID-19 patients, as self-reported by patients or measured through objective psychophysical tests. RESULTS: After the selection process, 155 studies were included, with a total of 70,920 patients and 105,291 not-infected individuals. Prevalence reports were extremely variable across studies, with wide ranges for OD (0%-98%) and GD (0-89%) prevalence. OGD occurred early during the disease course and only rarely preceded other symptoms; out of 30 studies with a follow-up time of at least 20 days, only in 5 studies OGD fully resolved in more than 90% of patients. OGD had low sensitivity and high specificity for SARS-CoV-2 infection; accuracy of OD and GD for infection identification was higher than 80% in 10 out of 33 studies and in 8 out of 22 studies considered, respectively. 28 out of 30 studies that studied the association between OGD and disease severity found how OGD were associated with lower rates of severe pneumonia, hospitalization and mortality. CONCLUSIONS: OGD seem to be highly prevalent in SARS-CoV-2 infection. They occur early, concomitantly with other symptoms and often persist after recovery, in some cases for months; whether a full recovery eventually occurs in all cases is not clear yet. OGD are good predictors of SARS-CoV-2 infection and are associated with a milder disease course.

Microstructural white matter alterations in borderline personality disorder: A minireview.

BACKGROUND: Borderline personality disorder (BPD) affects 1-5% of the population and is characterized by a complex symptomatology and selective functional impairments. Although brain imaging studies have contributed to better characterizing the pathophysiological mechanisms underlying BPD, the white matter (WM) deficits associated with this disorder are still unclear. Therefore, the present review aims at providing an overview of the findings emerged from the available diffusion tensor imaging (DTI) studies on BPD. METHODS: From a bibliographic research in PubMed until May 2019, we collected 12 studies that fulfilled our inclusion criteria, including a total sample of 291 BPD subjects and 293 healthy controls. RESULTS: Overall, the DTI studies reviewed showed impairments in selective WM tracts that are part of the prefronto-limbic system, including frontal WM (short and long tracts), anterior cingulate cortex, corpus callosum, corona radiata, hippocampal fornix and thalamic radiation, in BPD patients compared to healthy controls. LIMITATIONS: Few DTI studies with heterogeneous findings. CONCLUSIONS: Overall these results reported that BPD is characterized by selective structural connectivity alterations in prefronto-limbic structures, further supporting the neurobiological model of BPD that suggests the presence of an abnormal modulation of frontal regions over limbic structures. Finally, the results also highlighted that the disrupted WM integrity in selective brain regions may also explain key-aspects of BPD symptomatology, including emotional dysregulation, ambivalence, contradictory behaviors and cognitive dysfunctions.

A focus on valproate and cognitive deficits in Bipolar Disorders: A mini-review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

BACKGROUND: Cognitive deficits represent a core feature of Bipolar Disorder (BD), which seem to characterize this disorder regardless of the mood phase. However, the role of pharmacological treatment in determining cognitive alterations is still not clear. Indeed, although drugs improve cognition by targeting mood symptoms, they could also carry their own cognitive side effects. This is true especially for mood stabilizers as they are the most commonly prescribed drugs in patients affected by BD and they are usually administered also during euthymic phases. METHODS: In this context, the present review aimed at summarizing the results of the studies evaluating the impact of valproate on cognitive functions in patients suffering from BD, as primary or secondary results. The inclusion criteria were met by ten studies. Specifically, we included one double-blind quasi-randomized study and nine cross-sectional or naturalistic studies, which a) used healthy subjects as control group (N = 1), b) compared valproate treated patients with healthy individuals and other treatments (N = 5), and c) compared valproate treated patients just with other treatments, with a specific focus on lithium (N = 3). RESULTS: Overall the results suggested a negative effect of valproate on cognitive functions in chronically-treated patients affected by BD. Notably, it has been found that the working memory was the most affected cognitive domain. LIMITATIONS: Few studies directly explored the effect of valproate on cognition in BD. CONCLUSIONS: These findings seem to suggest that valproate might have a negative effect on cognitive functions, especially on working memory domain. However, the results should be taken cautiously since the limited number of available studies published so far. In conclusion, these evidences seem to point out that the possible cognitive side effects of pharmacological treatments should be carefully taken into account, especially in chronic patients.

Association between serum BDNF levels and maternal perinatal depression: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

INTRODUCTION: A large amount of studies demonstrated reduced serum Brain-Derived Neurotrophic Factor (BDNF) levels in stress-related and depressive disorders. However, it is still unclear if a similar deficit in BDNF concentrations might also characterize maternal perinatal depression. METHODS: We performed a bibliographic search on PUBMED of all the studies investigating the association between maternal BDNF levels and perinatal depression. The inclusion criteria were met by thirteen studies. RESULTS: Overall, the majority of the studies reported a significant reduction in serum BDNF levels among depressed mothers compared to healthy mothers either during pregnancy or in the postpartum period. Moreover, some studies also demonstrated that the BDNF reduction could be more evident in those depressed mothers with perinatal stressful life events and suicide risk. LIMITATIONS: BDNF were collected at different time points across the studies. Potential confounding factors, including the clinical characteristics of the samples employed by the original studies, might have influenced the results. CONCLUSIONS: So far, the evidences suggested the presence of decreased BDNF concentrations in perinatal depressive disorders. However, further studies are needed in order to confirm the role of BDNF in this disorder.

Intravenous valproate in the treatment of acute manic episode in bipolar disorder: A review.

BACKGROUND: Mania is a state of elated or irritable mood characterizing Bipolar Disorder type I (BD-I). Among the pharmacological treatments for the management of mania, mood stabilizers are regularly employed, with valproate being one of the most used because of its effectiveness. However, while the oral formulation is approved for acute mania, it is unclear whether the intravenous (IV) formulation could be a valid and safe alternative. METHODS: We performed a bibliographic research on PUBMED of all studies investigating the use of IV valproate as a treatment of acute mania in BD-I. A total of 13 studies met our inclusion criteria. RESULTS: Overall, the results suggest that IV valproate as a loading therapy is an efficacious, safe and well tolerated treatment for manic episodes, and it is comparable to the oral loading regimen. Interestingly, only a few patients experienced significant side effects due to the administration of the IV valproate. LIMITATIONS: Few open label clinical trials have explored the effect of IV valproate in manic patients. Moreover, the original studies employed different clinical assessments and included manic patients taking other drugs, which made it impossible to determine whether the resolution of symptoms was due to valproate therapy alone. Additionally, serum valproate levels were not assessed by all studies. CONCLUSIONS: IV valproate may represent a valid option for the management of acute mania, with comparable effects in terms of efficacy and safety to the oral valproate. However, larger and more homogeneous studies are warranted in order to collect more precise information on the beneficial effect of IV valproate.

Disease-discordant twin structural MRI studies on affective disorders.

Magnetic resonance imaging (MRI) studies have identified neural structures implicated in the pathophysiology of mood disorders, especially bipolar disorder (BD) and major depressive disorder (MDD). However, the role of genetic and environmental influences on such brain deficits is still unclear. In this context, the present review summarizes the current evidence from structural MRI and Diffusion Tensor Imaging (DTI) studies on twin samples concordant or discordant for BD or MDD, with the aim of clarifying the role of genetic and environmental risk factors on brain alterations. Although the results showed a complex interplay between gene and environment in affective disorders, the evidence seem to underline that both genetic and environmental risk factors have an impact on brain areas and vulnerability to MDD and BD. However, the precise mechanism of action and the interaction between these factors still needs to be unveiled. Therefore, future larger studies on concordant or discordant twins should be encouraged, because this population provides a unique opportunity to probe separately genetic and environmental markers of disease vulnerability.

Gray matter differences between affective and non-affective first episode psychosis: A review of Magnetic Resonance Imaging studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Non-affective and affective psychoses are very common mental disorders. However, their neurobiological underpinnings are still poorly understood. Therefore, the goal of the present review was to evaluate structural Magnetic Resonance Imaging (MRI) studies exploring brain deficits in both non-affective (NA-FEP) and affective first episode psychosis (A-FEP). METHODS: A bibliographic search on PUBMED of all MRI studies exploring gray matter (GM) differences between NA-FEP and A-FEP was conducted. RESULTS: Overall, the results from the available evidence showed that the two diagnostic groups share common GM alterations in fronto-temporal regions and anterior cingulate cortex. In contrast, unique GM deficits have also been observed, with reductions in amygdala for A-FEP and in hippocampus and insula for NA-FEP. LIMITATIONS: Few small MRI studies with heterogeneous methodology. CONCLUSIONS: Although the evidences are far to be conclusive, they suggest the presence of common and distinct pattern of GM alterations in NA-FEP and A-FEP. Future larger longitudinal studies are needed to further characterize specific neural biomarkers in homogenous NA-FEP and A-FEP samples.

MRI features of clinical outcome in bipolar disorder: A selected review: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Bipolar disorder (BD) is a severe and disabling mental illness, which is characterized by selective gray matter (GM) and white matter (WM) brain alterations, as observed by several imaging studies. However, the clinical course of the disease is uncertain and can vary across BD patients, with some having a benign course and others a severe disability. In this perspective, magnetic resonance imaging (MRI) can help identifying biological markers of worse prognosis. METHODS: The present selected review aimed at summarizing structural MRI (sMRI) studies exploring the correlation between brain morphology and features of clinical outcome, which could include treatment response, cognitive impairment and global functioning. RESULTS: Overall, the results from the reviewed sMRI studies reported that WM hyperintensities and GM volume reductions, mainly in fronto-limbic areas, correlate with worse outcome in BD. However, the selected outcome measures vary across studies, thus these observations cannot be conclusive. LIMITATIONS: Heterogeneity across studies and inconsistency on the outcome measures adopted limit the conclusion of the present review. Absence of widely shared definitions of outcome should be object of further research on BD in order to indicate more stable features of illness course. CONCLUSIONS: In summary, WM hyperintensities and fronto-temporo-limbic GM alterations may be potential indices of worse outcome in BD patients, particularly in terms of illness severity and progression. The identification of stable markers of prognosis can help the clinicians in selecting subgroups of bipolar patients who need specific treatment to preserve cognitive / psychosocial functioning, in the light of personalized approaches. To further characterize outcome in BD, future sMRI studies should a) longitudinally investigate patients with either poor or good course of the disease, and b) correlate neuroimaging measures with clinical, cognitive and genetic markers.

The impact of COMT polymorphisms on cognition in Bipolar Disorder: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Cognitive deficits represent a core feature of Bipolar Disorder. The dopamine system is considered fundamental for cognitive functions relying on prefrontal cortex, such as attention and executive functions. A genetic regulation of prefrontal dopamine has been described and the catechol-O-methyltransferase (COMT) has been extensively studied in relation to numerous psychiatric phenotypes, especially because of the involvement of its polymorphisms in the regulation of cognitive functions. Specifically, the Val158Met polymorphism greatly alters COMT function and cognitive performance in both psychiatric disorders and healthy controls. However, only few studies assessed the association between COMT polymorphisms and cognitive functions in bipolar disorder (BD) subjects and this association might help in the comprehension of cognitive alterations in BD. METHODS: In this context, the present review summarizes results from genetic studies that investigated COMT genetic modulation on cognitive performance in patients affected by BD. RESULTS: Overall the results confirmed that (a) COMT Val158Met polymorphism is associated with altered cognitive functions in BD patients, especially in the domains of memory, executive functions and emotion detection; and (b) COMT genotype may interact with both mood episodes and pharmacologic treatments in determining the cognitive profile of these subjects. LIMITATIONS: Few genetic studies exploring COMT genetic effect on cognition in BD. CONCLUSIONS: These findings seem to indicate a role of COMT polymorphisms in regulating cognitive functioning in patients with BD. The genetically determined dopaminergic tone may be further affected by mood episodes and pharmacological treatments.

The impact of BDNF Val66Met polymorphism on cognition in Bipolar Disorder: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Converging lines of evidence suggest that Brain-Derived Neurotrophic Factor (BDNF) may play a central role in the pathogenesis of Bipolar Disorder (BD), thus representing a valid biomarker of the disease. A common genetic variation in the BDNF gene, the Val66Met, is associated with reduced maturation and secretion of BDNF and therefore it has been related to specific mood, cognitive and neuroanatomical alterations in BD. However, so far, only a handful of studies have investigated the association between Val66Met polymorphism and cognitive functioning in BD. METHODS: We performed a bibliographic search on PUBMED of all genetic studies investigating Val66Met modulation on cognitive performances in BD subjects. The inclusion criteria were met by nine studies, including a total amount of 897 BD subjects and 803 healthy controls. RESULTS: From the analysis of the existing literature emerged that a) Val allele in BD adults, but not in BD adolescents, was associated with better performances in selective cognitive domains including executive functions, verbal learning and memory; b) Met allele may negatively modulate the association between childhood trauma and performances in memory, verbal ability and verbal fluency tasks; c) Met allele may also negatively regulate structural abnormalities in cognitive cerebral structures; d) Val/Met carriers showed greater improvements in cognitive functions compared to Val/Val and Met/Met carriers. LIMITATIONS: Few genetic studies exploring the impact of Val66Met on cognition in BD. CONCLUSIONS: Val66Met polymorphism likely modulates cognitive functions in BD patients with complex gene-environment interactions and through potential modulations of cerebral structures. Further and larger genetic studies are required in order to detect association between BDNF polymorphism, BDNF levels, brain abnormalities and cognition in BD.

Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview.

Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

The role of genes and environment on brain alterations in Major Depressive Disorder: A review of twin studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Although it has been consistently reported the important role of genetic and environmental risk factors on structural and functional alterations in Major Depressive Disorder (MDD), the mechanism and the magnitude of the interactions between specific genetic and/or environmental risk factors on brain structures in this disabling disorder are still elusive. Therefore, in the last two decades an increased interest has been devoted to neuroimaging investigations on monozygotic and dizygotic twin samples mainly because their intrinsic characteristics may help to separate the effects of genetic and environmental risk factors on clinical phenotypes, including MDD. METHODS: In this context, the present review summarizes results from structural and functional Magnetic Resonance Imaging studies that investigated twin samples in correlation with MDD. RESULTS: Overall the results confirmed that a) MDD is characterized by significant alterations in selective brain areas presiding over emotion recognition and evaluation, including amygdala, insula and prefrontal cortices, and b) both genetic and environmental risk factors play a key role in the pathophysiology of this disorder. LIMITATIONS: Few MRI studies exploring MDD in twin samples. CONCLUSIONS: The specific contribution of both aspects is still not fully elucidated especially because genes and environment have an impact on the same brain areas, which are particularly vulnerable in MDD. Expansion of the current twin sample sizes would help to clearly establish the potential relationship between risk factors and the development of MDD.

Metabolic alterations in generalised anxiety disorder: a review of proton magnetic resonance spectroscopic studies.

Generalised anxiety disorder (GAD) is a common psychiatric illness characterised by selective morpho-functional brain alterations. The breath of neuroimaging studies investigating the neural basis of GAD is extensive; however, its pathophysiology is still largely unknown. Specifically for proton Magnetic Resonance Spectroscopy (¹H MRS) investigations, which have the aim of identifying differences in metabolite levels between conditions in key brain areas, often showed contrasting results. Indeed, there are selected ¹H MRS studies reporting deficits of key metabolites in GAD patients; however, collectively the literature remains mixed with respect to consistency of major findings. In this review, we evaluate published ¹H MRS studies on GAD with the final aim of providing a comprehensive overview of the extent of neurometabolic dysfunctions associated with GAD. Interestingly, the majority of the studies reviewed showed altered metabolite levels in the dorsolateral prefrontal cortex and hippocampus suggesting regional specificity. These results also provide evidence of the utility of ¹H MRS not only for elucidating the pathophysiology of neuropsychiatric diseases, but also for the identification of more beneficial and targeted pharmacological interventions. Additionally, future studies are warranted to overcome methodological differences observed across the studies.

Pituitary gland in Bipolar Disorder and Major Depression: Evidence from structural MRI studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summarise relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: The function of the hypothalamo-pituitary-adrenal axis (HPA) has been widely investigated in mood disorders based on its role in regulating stress response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder (MDD). In this context, the present review summarizes the results from MRI studies with the final aim of commenting on the presence of common or distinct PG structural alterations between these two disabling illnesses. METHODS: A bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was performed. RESULTS: Following the screening process of the available literature it can be said that a) PG enlargement has been found in both BD and MDD, therefore potentially representing a common neurobiological marker characterizing mood disorders, and b) PG volumes are moderated by age and sex in both illnesses, although the direction and the extent of this moderation are still not fully clear. LIMITATIONS: Few MRI studies with heterogeneous results. CONCLUSIONS: These hypotheses must be taken with caution especially because the heterogeneity of the results of the studies reviewed does not allow for a definite answer about the role of PG in affective disorders. Therefore, larger longitudinal studies investigating PG volumes in BD and MDD patients at the early phases of the illness, by considering females and males separately, are needed to further corroborate these findings.

Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study.

BACKGROUND: Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET). METHODS: Twenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired. RESULTS: Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients. CONCLUSIONS: These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.