Biomarker-Guided Tailored Therapy in Major Depression.

This chapter provides a comprehensive examination of a broad range of biomarkers used for the diagnosis and prediction of treatment outcomes in major depressive disorder (MDD). Genetic, epigenetic, serum, cerebrospinal fluid (CSF), and neuroimaging biomarkers are analyzed in depth, as well as the integration of new technologies such as digital phenotyping and machine learning. The intricate interplay between biological and psychological elements is emphasized as essential for tailoring MDD management strategies. In addition, the evolving link between psychotherapy and biomarkers is explored to uncover potential associations that shed light on treatment response. This analysis underscores the importance of individualized approaches in the treatment of MDD that integrate advanced biological insights into clinical practice to improve patient outcomes.

How to treat subsyndromal anxiety disorder - practical recommendations for implementation in primary care.

BACKGROUND: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings. METHODS: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA. RESULTS: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA. CONCLUSION: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.

Anxiety is prevalent and disablingSubsyndromal anxiety is a risk factor for anxiety disordersSubsyndromal anxiety can be assessed with the GAD-7 (Generalised Anxiety Disorder-7 scale)Subsyndromal anxiety can be treated with life-style modification, psychotherapy and pharmacological treatment, including silexan, a natural compound.

Predicting New-Onset Psychiatric Disorders Throughout the COVID-19 Pandemic: A Machine Learning Approach.

OBJECTIVE: The investigators estimated new-onset psychiatric disorders (PsyDs) throughout the COVID-19 pandemic in Italian adults without preexisting PsyDs and developed a machine learning (ML) model predictive of at least one new-onset PsyD in subsequent independent samples. METHODS: Data were from the first (May 18-June 20, 2020) and second (September 15-October 20, 2020) waves of an ongoing longitudinal study, based on a self-reported online survey. Provisional diagnoses of PsyDs (PPsyDs) were assessed via DSM-based screening tools to maximize assessment specificity. Gradient-boosted decision trees as an ML modeling technique and the SHapley Additive exPlanations technique were applied to identify each variable's contribution to the model. RESULTS: From the original sample of 3,532 participants, the final sample included 500 participants in the first wave and 236 in the second. Some 16.0% of first-wave participants and 18.6% of second-wave participants met criteria for at least one new-onset PPsyD. The final best ML predictive model, trained on the first wave, displayed a sensitivity of 70% and a specificity of 73% when tested on the second wave. The following variables made the largest contributions: low resilience, being an undergraduate student, and being stressed by pandemic-related conditions. Living alone and having ceased physical activity contributed to a lesser extent. CONCLUSIONS: Substantial rates of new-onset PPsyDs emerged among Italians throughout the pandemic, and the ML model exhibited moderate predictive performance. Results highlight modifiable vulnerability factors that are suitable for targeting by public campaigns or interventions to mitigate the pandemic's detrimental effects on mental health.

Personalized Clinical Approaches to Anxiety Disorders.

Anxiety disorders (ADs) are common psychiatric disorders, with a lifetime prevalence estimated at 33.7% in epidemiological studies. ADs are associated with serious disability and severe impairment in quality of life. Although several treatments [e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin, tricyclic antidepressants and benzodiazepines and/or cognitive-behaviour therapy (CBT)] are recommended, a large number of patients (i.e. from 30 to 70%) do not achieve complete remission. According to the novel paradigm of personalized medicine, the search of possible predictors of both disease vulnerability and treatment response might be the best way to prevent more accurately disease risk and to tailor the most effective treatment for each individual. Although a growing body of studies have proposed several endophenotypes/markers (i.e. neurochemical, neuroimaging, physiological, genetic and epigenetic endophenotypes/markers) as possible predictors of ADs susceptibility and/or treatment response, findings are not robust enough to be considered acceptable to incorporate in the clinical practice. In order to obtain more reliable results, larger studies with a multimodal approach, based on a combination of different biomarkers, are needed.

'Precision' or 'personalized' psychiatry: different terms - same content?

Due to the increased lifetime prevalence and personal, social, and economic burden of mental disorders, psychiatry is in need of a significant change in several aspects of its clinical and research approaches. Over the last few decades, the development of personalized / precision medicine in psychiatry focusing on tailored therapies that fit each patient's unique individual, physiological, and genetic profile has not achieved the same results as those obtained in other branches, such as oncology. The long-awaited revolution has not yet surfaced. There are various explanations for this including imprecise diagnostic criteria, incomplete understanding of the molecular pathology involved, absence of available clinical tools and, finally, the characteristics of the patient. Since then, the co-existence of the two terms has sparked a great deal of discussion around the definition and differentiation between the two types of psychiatry, as they often seem similar or even superimposable. Generally, the two terminologies are used indiscriminately, alternatively, and / or separately, within the same scientific works. In this paper, an overview is provided on the overlap between the application and meaning of the terms 'precision psychiatry' and 'personalized psychiatry'.

Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday 'real world' clinical practice.

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

Mental health professionals' attitudes towards mental illness: professional and cultural factors in the INTER NOS study.

BACKGROUND: Research shows that personnel working in mental health facilities may share some of the societal prejudices towards mental illness. This might result in stigmatizing behaviours towards people suffering from mental disorders, undermining the quality of their care. AIMS: To describe and compare attitudes towards mental illness across a sample of professionals working in a wide range of mental health facilities in Spain, Portugal and Italy. METHOD: We administered a survey to personnel including two questionnaires related to stigmatizing attitudes: The Community Attitudes toward the Mentally Ill (CAMI) and the Attribution Questionnaire (AQ-27). Data were compared according to professional category, work setting and country. RESULTS: 34.06% (1525) professionals of the surveyed population responded adequately. Psychologists and social therapists had the most positive attitudes, and nursing assistants the most negative, on most factors of CAMI and AQ-27. Community staff had more positive attitudes than hospital-based professionals in most factors on CAMI and in discriminatory responses on AQ-27. CONCLUSIONS: Globally, mental health professionals showed a positive attitude towards mental illness, but also a relative support to coercive treatments. There are differences in attitudes modulated by professional category and setting. Results can guide preventive strategies, particularly for the hospital-based and nursing staff.

A clinically-translatable machine learning algorithm for the prediction of Alzheimer's disease conversion: further evidence of its accuracy via a transfer learning approach.

BACKGROUND: In a previous study, we developed a highly performant and clinically-translatable machine learning algorithm for a prediction of three-year conversion to Alzheimer's disease (AD) in subjects with Mild Cognitive Impairment (MCI) and Pre-mild Cognitive Impairment. Further tests are necessary to demonstrate its accuracy when applied to subjects not used in the original training process. In this study, we aimed to provide preliminary evidence of this via a transfer learning approach. METHODS: We initially employed the same baseline information (i.e. clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy) and the same machine learning technique (support vector machine with radial-basis function kernel) used in our previous study to retrain the algorithm to discriminate between participants with AD (n = 75) and normal cognition (n = 197). Then, the algorithm was applied to perform the original task of predicting the three-year conversion to AD in the sample of 61 MCI subjects that we used in the previous study. RESULTS: Even after the retraining, the algorithm demonstrated a significant predictive performance in the MCI sample (AUC = 0.821, 95% CI bootstrap = 0.705-0.912, best balanced accuracy = 0.779, sensitivity = 0.852, specificity = 0.706). CONCLUSIONS: These results provide a first indirect evidence that our original algorithm can also perform relevant generalized predictions when applied to new MCI individuals. This motivates future efforts to bring the algorithm to sufficient levels of optimization and trustworthiness that will allow its application in both clinical and research settings.

The role of spatial store and executive strategy in spatial working memory: a comparison between patients with obsessive-compulsive disorder and controls.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM. METHODS: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: α = 0.05. RESULTS: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance. CONCLUSIONS: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.

Reduced cortical thickness and increased gyrification in generalized anxiety disorder: a 3 T MRI study.

BACKGROUND: Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD. METHODS: A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs. RESULTS: Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed. CONCLUSIONS: Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Features of mood associated with high body weight in females with fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a common syndrome whose main characteristic is chronic widespread musculoskeletal pain, the severity of which is frequently worsened by concomitant obesity. Major depression (MD), particularly as part of a bipolar spectrum disorder (BSD), is associated with both obesity and FM. OBJECTIVE: To evaluate the relationship between lifetime MD, hypomanic symptoms and the body mass index (BMI) in patients with FM. METHOD: Of the 115 patients originally screened, 87 women with FM finally entered the study. Forty-nine patients (57%) had a lifetime diagnosis of MD, assessed by a structured clinical interview based on DSM-IV criteria, and four of them (4.6%) had a current MD episode. Lifetime hypomanic symptoms were measured by means of the self-rated Hypomania Checklist. According to the international criteria for BMI, FM patients were classified as under/normal-weight (61%), overweight (30%) and obese (9%). RESULTS: 62 patients (71.2%) with FM had a bipolar spectrum disorder (BSD). Thirty (48.3%) of them met criteria for bipolar II disorder, 32 (51,6%) for bipolar disorder NOS (18 FM patients with MD associated to sub-syndromal hypomanic syndrome and 14 with hypomanic syndrome without MD). No patient had a bipolar I disorder. Only one patient met the criteria for a major depressive disorder (MDD). There was no significant difference in mean BMI between the patients with and without a lifetime diagnosis of MD, but there was a positive association between the level of hypomanic symptoms and BMI values (p<0.009). When hypomania was considered categorically as hypomanic syndrome there was no significant effect on BMI. CONCLUSIONS: Our finding adds to previous evidence indicating that hypomanic symptoms are a central feature of FM. In the case of the early identification of high-level hypomanic symptoms, body weight should be closely monitored in order to prevent obesity and its detrimental impact on females with FM.

Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors.

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.

Childhood adversities in patients with fibromyalgia: are they related to comorbid lifetime major depression?

OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology that is frequently associated with depressive disorders, and childhood adversities (including maltreatment and parental loss) are frequently described in subjects with FM and depression. The aim of this study was to investigate the extent to which the high percentage of childhood adversities reported by patients with FM is related to FM itself or to a comorbid lifetime depressive disorder. METHODS: Ninety-four consecutive FM patients were assessed for lifetime major depression using the DSM-IVSCID-CV interview. Childhood maltreatment was investigated using the Childhood Trauma Questionnaire, and information relating to parental death or separation before the age of 18 years was collected by means of a semi-structured interview. The Zung Self-Rating Depression Scale, used as a quantitative measure of depressive symptoms, and the childhood adversity assessment were recorded at the same time. RESULTS: Sixty of the 94 FM patients (63.8%) were diagnosed as having a lifetime major depressive disorder. There were no significant associations between childhood parental loss, the presence/level of maltreatment, the occurrence of a lifetime major depression episode, and the Zung Self-Rating Depression Scale scores. CONCLUSIONS: The results of this study suggest that there is no association between childhood adversities and comorbid lifetime major depression in patients with FM. As it would be helpful to prevent the development of FM because of the high cost and limited efficacy of therapeutic interventions, childhood adversities may offer targets for primary prevention.

Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: an exploratory study in "real-world," everyday clinical practice.

OBJECTIVE: Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients. METHODS: 30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in "real-world," everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment. RESULTS: Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose. CONCLUSIONS: Agomelatine's antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

The burden of mood-disorder/cerebrovascular disease comorbidity: essential neurobiology, psychopharmacology, and physical activity interventions.

Cardio-vascular diseases (CVDs) and CVD-related disorders (including cerebrovascular diseases; CBVDs) are a major public health concern as they represent the leading cause of mortality and morbidity in developed countries. Patients with CVDs and CBVDs co-morbid with mood disorders, especially bipolar disorder (BD) and major depressive disorder (MDD), suffer reduced quality-of-life and significant disability adjusted for years of life and mortality. The relationship between CVDs/CBVDs and mood disorders is likely to be bidirectional. Evidence for shared genetic risk of pathways involved in stress reaction, serotonin or dopamine signalling, circadian rhythms, and energy balance was reported in genome-wide association studies. There is some evidence of a neuroprotective effect of various antidepressants, which may be boosted by physical exercise, especially by aerobic ones. Patients with CVDs/CBVDs should be routinely attentively evaluated for the presence of mood disorders, with tools aimed at detecting both symptoms of depression and of hypomania/mania. Behavioural lifestyle interventions targeting nutrition and exercise, coping strategies, and attitudes towards health should be routinely provided to patients with mood disorders, to prevent the risk of CVDs/CBVDs. A narrative review of the evidence is herein provided, focusing on pharmacological and physical therapy interventions.

Latent classes of emotional and behavioural problems in epidemiological and referred samples and their relations to DSM-IV diagnoses.

Researchers' interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N = 1225), of the general-population sample (N = 3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.

The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Is panic disorder associated with clinical severity of fibromyalgia? A preliminary study in a tertiary-care centre.

OBJECTIVES: To investigate the influence of panic disorder (PD) with/without agoraphobia on the clinical severity of fibromyalgia (FM). METHODS: Eighty-one patients with FM, among those consecutively referring to a tertiary-care setting, were included in this cross-sectional study. Psychiatric diagnoses were made by the structured clinical interview in accordance with the 4th-TR version of the diagnostic and statistical manual of mental disorders. The clinical severity of FM was measured by means of the following self-administered scales: Fibromyalgia Impact Questionnaire (FIQ), Fibromyalgia Assessment Status (FAS), Health Assessment Questionnaire (HAQ). RESULTS: A final sample of 66 females with FM with or without past PD was included in the analyses. The two groups did not significantly differ in age, years of education, length of illness or medication distribution. We did not find significant differences between the two groups in the FIQ and FAS scale scores, whereas subjects with FM and past PD showed significantly higher HAQ scale scores than those without past PD (p<.001). CONCLUSIONS: A history of PD in patients with FM increases the severity of functional impairment in performing a wide range of daily-life activities, as measured by the HAQ scale, with no effects on the severity of other clinical dimensions of FM. Potential underlying mechanisms and clinical implications will be discussed.

Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features.

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression.

Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aß accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed.