Machine learning applied to functional magnetic resonance imaging in anxiety disorders.

BACKGROUND: Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, and specific phobias. The role of functional abnormalities in the discrimination of these disorders can be tested with machine learning (ML) techniques. Here, we aim to provide a comprehensive overview of ML studies exploring the potential discriminating role of functional brain alterations identified by functional magnetic resonance imaging (fMRI) in anxiety disorders. METHODS: We conducted a search on PubMed, Web of Science, and Scopus of ML investigations using fMRI as features in patients with anxiety disorders. A total of 12 studies (resting-state fMRI n = 5, task-based fMRI n = 6, resting-state and task-based fMRI n=1) met our inclusion criteria. RESULTS: Overall, the studies showed that, regardless of the classifiers, alterations in functional connectivity and aberrant neural activation involving the amygdala, anterior cingulate cortex, hippocampus, insula, orbitofrontal cortex, temporal pole, cerebellum, default mode network, dorsal attention network, sensory network, and affective network were able to discriminate patients with anxiety from controls, with accuracies spanning from 36 % to 94 %. LIMITATIONS: The small sample size, different ML approaches and heterogeneity in the selection of regions included in the multivariate pattern analyses limit the conclusions of the present review. CONCLUSIONS: ML methods using fMRI as features can distinguish patients with anxiety disorders from healthy controls, indicating that these techniques could be used as a helpful tool for the diagnosis and the development of more targeted treatments for these disorders.

Economic impact of reducing treatment gaps in depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent across Europe. While evidence-based treatments exist, many people with MDD have their condition undetected and/or untreated. This study aimed to assess the cost-effectiveness of reducing treatment gaps using a modeling approach. METHODS: A decision-tree model covering a 27-month time horizon was used. This followed a care pathway where MDD could be detected or not, and where different forms of treatment could be provided. Expected costs pertaining to Germany, Hungary, Italy, Portugal, Sweden, and the UK were calculated and quality-adjusted life years (QALYs) were estimated. The incremental costs per QALY of reducing detection and treatment gaps were estimated. RESULTS: The expected costs with a detection gap of 69% and treatment gap of 50% were €1236 in Germany, €476 in Hungary, €1413 in Italy, €938 in Portugal, €2093 in Sweden, and €1496 in the UK. The incremental costs per QALY of reducing the detection gap to 50% ranged from €2429 in Hungary to €10,686 in Sweden. The figures for reducing the treatment gap to 25% ranged from €3146 in Hungary to €13,843 in Sweden. CONCLUSIONS: Reducing detection and treatment gaps, and maintaining current patterns of care, is likely to increase healthcare costs in the short term. However, outcomes are improved, and reducing these gaps to 50 and 25%, respectively, appears to be a cost-effective use of resources.

Neuroimaging Correlates of Treatment Response to Transcranial Magnetic Stimulation in Bipolar Depression: A Systematic Review.

Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions for studies investigating neuroimaging biomarkers, through structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT), in association with response to TMS in patients with BD. Eleven studies were included (fMRI = 4, MRI = 1, PET = 3, SPECT = 2, and MRS = 1). Important fMRI predictors of response to repetitive TMS (rTMS) included higher connectivity of emotion regulation and executive control regions. Prominent MRI predictors included lower ventromedial prefrontal cortex connectivity and lower superior frontal and caudal middle frontal volumes. SPECT studies found hypoconnectivity of the uncus/parahippocampal cortex and right thalamus in non-responders. The post-rTMS changes using fMRI mostly showed increased connectivity among the areas neighboring the coil. Increased blood perfusion was reported post-rTMS in PET and SPECT studies. Treatment response comparison between unipolar depression and BD revealed almost equal responses. Neuroimaging evidence suggests various correlates of response to rTMS in BD, which needs to be further replicated in future studies.

Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study.

BACKGROUND: Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. MATERIAL AND METHODS: 68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. RESULTS: At baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. CONCLUSIONS: The longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders.

Case Report: Repeated Transcranial Magnetic Stimulation Improves Comorbid Binge Eating Disorder in Two Female Patients With Treatment-Resistant Bipolar Depression.

Introduction: Binge eating disorder (BED) is the most common eating disorder, affecting a large population worldwide. It is characterized by recurrent episodes of binge eating, with no compensatory behaviors. BED is often associated with psychiatric comorbidities, and still represents a challenge in terms of treatment strategies. In the last years, neuromodulation has represented a promising approach in the treatment of BED. We report the cases of two women, affected by Bipolar Disorder Type II (BD-II) and comorbid BED, whose BED symptoms improved after a course of accelerated intermittent Theta Burst Stimulation (iTBS). Methods: We carried out a clinical study, involving neurostimulation on six patients with a treatment-resistant depressive episode. The trial consisted of a 3-week accelerated iTBS treatment, delivered to the left dorsolateral pre-frontal cortex. Clinical evaluation scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Young Mania Rating Scale) were administered at baseline, after 2 weeks, and at the end of the stimulation cycle. Pharmacotherapy was maintained unchanged during iTBS treatment. Patients gave their informed consent both for the protocol and for the publication. Results: The treatment was well-tolerated. Depressive symptoms only slightly improved; however, patients' binge episodes remitted completely, which was a serendipitous finding. BED symptomatology complete remission lasted up to 12 weeks follow-up. Discussion: This is the first study regarding iTBS use in BED in comorbidity with BD-II. Further research is still needed to assess the efficacy of this technique in BED treatment.

Use of 30-Hz Accelerated iTBS in Drug-Resistant Unipolar and Bipolar Depression in a Public Healthcare Setting: A Case Series.

Background: Depressive episodes, especially when resistant to pharmacotherapy, are a hard challenge to face for clinicians and a leading cause of disability worldwide. Neuromodulation has emerged as a potential therapeutic option for treatment-resistant depression (TRD), in particular transcranial magnetic stimulation (TMS). In this article, we present a case series of six patients who received TMS with an accelerated intermittent theta-burst stimulation (iTBS) protocol in a public healthcare setting. Methods: We enrolled a total number of six participants, affected by a treatment-resistant depressive episode, in either Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Patients underwent an accelerated iTBS protocol, targeted to the left dorsolateral prefrontal cortex (DLPFC), 3-week-long, with a total of 6 days of overall stimulation. On each stimulation day, the participants received 3 iTBS sessions, with a 15-min pause between them. Patients were assessed by the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Mania Rating Scale (MRS). At baseline (T0), at the end of the second week (T1), and at the end of the cycle of stimulation (T2). Results: The rANOVA (repeated Analysis of Variance) statistics showed no significant effect of time on the rating scale scores, with a slight decrease in MADRS scores and a very slight increase in HAM-A and HAM-D scores. No manic symptoms emerged during the entire protocol. Conclusions: Although accelerated iTBS might be considered a less time-consuming strategy for TMS administration, useful in a public healthcare setting, our results in a real-word six-patient population with TRD did not show a significant effect. Further studies on wider samples are needed to fully elucidate the potential of accelerated iTBS protocols in treatment-resistant depression.

Role of rTMS in the treatment of cognitive impairments in Bipolar Disorder and Schizophrenia: a review of Randomized Controlled Trials.

BACKGROUND: Schizophrenia (SCZ) and Bipolar Disorder (BD) are severe psychiatric illnesses often characterized by mild-to-severe cognitive deficits. Since available pharmacotherapy showed poor efficacy in treating these cognitive impairments, new strategies are needed. Repeated Transcranial Magnetic Stimulation (rTMS) represents a safe non-invasive technique that has been hypothesized to improve cognitive symptoms in these pathologies. Therefore, our brief review aims at summarizing the results of Randomized Controlled Trials (RCTs) using rTMS for improving cognitive symptoms in SCZ and BD. METHODS: We performed a bibliographic research on PubMed, Google Scholar and Medline of RCTs conducted in patients with BD and SCZ, which evaluated cognitive outcomes after rTMS treatment. RESULTS: The inclusion criteria were met by fifteen RCTs, twelve in SCZ and three in BD. Regarding patients with SCZ, the results showed that rTMS seemed to have poor effects on improving cognitive performances, with mixed results also observed for schizoaffective patients. In BD, overall the RCTs showed that rTMS in these patients seemed to improve cognitive domains in euthymic patients, while its effect during acute phases, especially depression, appeared limited. LIMITATIONS: Studies employed different rTMS protocols and evaluated different cognitive domains. CONCLUSIONS: Although the available evidence from RCTs evaluating the efficacy of rTMS on cognitive deficits in SCZ and BD are still mixed and heterogenous, overall they suggest that rTMS represents a potential clinical tool that could ameliorate cognitive symptoms, especially in specific patients' subtypes. However, standardized protocols and further research are still necessary to evaluate the real efficacy of rTMS.

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study.

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

Transcranial magnetic stimulation in major depressive disorder: Response modulation and state dependency.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) has emerged as a valid therapeutic option in the treatment of depression, especially in cases of inadequate response to antidepressant agents. Despite the recognized efficacy of this technique, its mechanisms of action are still debated and optimal protocols have not yet been established. METHODS: The present review focuses on TMS protocols that either engage the targeted brain circuits or synchronize the stimulation frequency to individual neuronal oscillations to increase the antidepressant efficacy. RESULTS: TMS efficacy was found to be enhanced by preliminary or concomitant modulation of the functional state of the targeted brain networks. Conversely, there is not enough evidence of higher efficacy of TMS protocols with individual selection of the stimulation frequency compared to standard ones. LIMITATIONS: Most studies included small patient samples. CONCLUSIONS: Our results suggest that a good option to enhance rTMS efficacy might be to follow synaptic potentiation and depression rules.

Transcranial direct current stimulation modulates implicit attitudes towards food in eating disorders.

OBJECTIVE: Neuromodulation of regions involved in food processing is increasingly used in studies on eating behaviors, but results are controversial. We assessed the effects of anodal transcranial direct current stimulation (a-tDCS) on food and body implicit preferences in patients with eating disorders (EDs). METHOD: Thirty-six ED patients and 36 healthy females completed three sessions with a-tDCS applied to the medial-prefrontal cortex (mPFC), the right extrastriate body area (rEBA) or in sham mode. Each participant then completed three Implicit Association Tests (IATs) on tasty/tasteless food, underweight/overweight body images, flowers versus insects as control. Differences in latency between incongruent and congruent blocks were calculated (D score). RESULTS: The tDCS by group interaction was significant for the IAT-food D score, with patients showing weaker preference for tasty food than controls in sham, but not a-tDCS sessions. In particular, rEBA stimulation significantly increased patients' D score compared to sham. Moreover, a-tDCS over mPFC and rEBA selectively increased patients' reaction times in the incongruent blocks of the IAT-food. DISCUSSION: A-tDCS on frontal and occipito-temporal cortices modulated food preferences in ED patients. The effect was specific for food images and selective in patients, but not in healthy participants. These findings suggest that neuromodulation of these regions could affect implicit food attitudes.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

BACKGROUND: It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. METHODS: We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. RESULTS: Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. CONCLUSIONS: Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms.