The use of antipsychotics in obsessive compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic disease with a prevalence in the general population of around 2%-3%, generally accompanied by a severe impairment of functioning and quality of life. A consistent subgroup of patients may not achieve adequate symptom remission with first-line treatments (i.e., cognitive behavioral therapy, selective serotonin reuptake inhibitors [SSRIs]). The most validated option for treatment-resistant cases relies on the augmentative use of antipsychotics to SSRIs, preferably of the 'second generation'. Indeed, dopamine appears to be crucially involved in OCD neuropathology due to its implication in systems relating to goal-directed behaviour and maladaptive habits. Nevertheless, the mechanism of action of antipsychotics in OCD symptom improvement is still unclear. Risperidone, aripiprazole, and haloperidol seem to be the most useful medications, whereas 'first generation' antipsychotics may be indicated in case of comorbidity with tics and/or Tourette Syndrome. Antipsychotic augmentation may be also related to side-effects, particularly in the long term (e.g., alteration in metabolic profile, sedation, extrapyramidal symptoms). The present mini-review sought to provide the most updated evidence on augmentative antipsychotic use in treatment-resistant patients with OCD, providing a road map for clinicians in daily practice and shedding light on avenues for further research.

Assessing response, remission, and treatment resistance in patients with obsessive-compulsive disorder with and without tic disorders: results from a multicenter study.

BACKGROUND: Highlighting the relationship between obsessive-compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new "tic-related" specifier for OCD, ie, obsessive-compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics. METHODS: A sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response. RESULTS: The remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement. CONCLUSIONS: Although remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

The role of gender in a large international OCD sample: A Report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) Network.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD. METHODS: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS). RESULTS: Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity. DISCUSSION/CONCLUSIONS: Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.

Suicidal ideation and suicidal attempts in patients with obsessive-compulsive tic-related disorder vs obsessive-compulsive disorder: results of a multicenter Italian study.

BACKGROUND: Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD. METHODS: Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA). RESULTS: No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups. CONCLUSIONS: Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

Bipolar disorder staging and the impact it has on its management: an update.

INTRODUCTION: The longitudinal course of bipolar disorder (BD) is associated with an active process of neuroprogression, characterized by structural brain alterations and progressive functional impairment. In the last decades, a growing need of a standardized staging model for BD arose, with the aim of a more appropriate definition of stage-specific clinical manifestations and the identification of more customized therapeutic tools. AREAS COVERED: The authors review the literature on clinical aspects, neurobiological correlates and treatment issues related to BD progression. Thereafter, they address the definition, constructs, and evolution of the staging concept, focusing on the clinical applications of BD staging models available in literature. EXPERT OPINION: Although several staging models for BD have been proposed to date, their application in clinical practice is still relatively scant. This may have a detrimental impact on the clinical and therapeutic management of BD, in terms of early and proper diagnosis as well as tailored treatment interventions according to the different stages of illness. Future research efforts should tend to the integration of recent insights on neuroimaging and epigenetic markers, toward a standardized and multidimensional staging model.

The progression trajectory of Bipolar Disorder: results from the application of a staging model over a ten-year observation.

BACKGROUND: Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a previous article we retrospectively applied the main staging models to a sample of 100 bipolar patients at four time points over a ten-year observation. In the present study, focusing on Kupka & Hillegers's model, we aimed to assess the transition of the same sample through the different stages of illness and to explore the potential role of clinical variables on the risk of progression. METHODS: Multistate Model using the mstate package in R and Markov model with stratified hazards were used for statistical analysis. RESULTS: A high hazard of transition from stage 2 to 3 emerged, with a probability of staying in stage 2 decreasing to 14 % after 3 years. BD II was significantly associated with transition from stage 1 to 2, whereas the number of lifetime episodes >3 and the elevated predominant polarity with transition from stage 3 to 4. CONCLUSION: Our results corroborated the evidence on BD progression and contributed to outline its trajectory over time. Further effort may help to define a standardized staging approach towards ever increasing tailored interventions.

Early-onset obsessive-compulsive disorder: Sociodemographic and clinical characterization of a large outpatient cohort.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology, course, and comorbidities. Early-onset OCD (EO) could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression. To deepen the heterogeneous nature of the disorder, we analyzed sociodemographic and clinical differences between the EO and late-onset (LO) subtypes in a large outpatient cohort. METHODS: Two hundred and eighty-four patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO, age <18 years [n = 117,41.2 %]; LO: late-onset, age ≥18 years [n = 167, 58.8 %]). RESULTS: The EO group showed a higher frequency of male gender (65 % vs 42.5 %, p < .001), and a higher prevalence of Tic and Tourette disorders (9.4 % vs 0 %, p < .001) compared to the LO group. Additionally, in the EO subgroup, a longer duration of untreated illness was observed (9.01 ± 9.88 vs 4.81 ± 7.12; p < .001), along with a lower presence of insight (13.8 % vs. 7.5 %, p < .05). CONCLUSIONS: The early-onset OCD subtype highlights a more severe clinical profile compared to the LO group. Exploring distinct manifestations and developmental trajectories of OCD can contribute to a better definition of homogeneous subtypes, useful for defining targeted therapeutic strategies for treatment.

Clinical features in co-occuring obsessive-compulsive disorder and bipolar disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) frequently co-occurs with various psychiatric conditions and may impact as many as one-fifth of individuals diagnosed with bipolar disorder (BD). Despite the expanding body of literature on the coexistence of OCD and BD, there is a notable lack of comprehensive data pertaining to the distinct features of obsessive-compulsive symptoms that define this comorbidity. To bridge this knowledge gap, we conducted a systematic search of PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO until August 7th, 2023. We performed random-effects meta-analyses to compare individuals with both OCD and BD to those with OCD in terms of OCD symptomatology as well as the specific categories of obsessions and compulsions. Out of the 10,393 records initially screened, 17 studies were ultimately incorporated into the qualitative assessment, with 15 of them being included in the quantitative analysis. Individuals with OCD and BD experienced fewer lifetime contamination obsessions (OR=0.71; 95 %CI=0.53, 0.95; p = 0.021) and more sexual obsessions (OR=1.77; 95 %CI=1.03, 3.04; p = 0.04) compared to individuals with OCD without BD. No significant difference was observed for other types of obsessions or compulsions or for the severity of OCD symptoms, although BD type may play a role according to meta-regression analyses. The detection of the presence of sexual or contamination obsessions through a detailed interview may be the focus of clinical attention when assessing OCD in the context of comorbid BD. Sub-phenotyping complex clinical presentation of comorbid psychiatric disorders can aid in making more informed decisions when choosing an appropriate treatment approach.

Treatment adherence rates across different psychiatric disorders and settings: findings from a large patient cohort.

Approximately 50% of patients with psychiatric disorders do not fully adhere to the prescribed psychopharmacological therapy, significantly impacting the progression of the disorder and the patient's quality of life. The present study aimed to assess potential differences in terms of rates and clinical features of treatment adherence in a large cohort of psychiatric patients with different diagnoses attending various psychiatric services. The study included 307 psychiatric patients diagnosed with a primary major depressive disorder, bipolar disorder, anxiety disorder, schizophrenic spectrum disorder, or personality disorder. Patient's adherence to treatment was evaluated using the Clinician Rating Scale, with a cutoff of at least five defining adherence subgroups. One-third of the sample reported poor medication adherence. A lower rate of adherence emerged among patients with schizophrenic spectrum disorder and bipolar disorder. Subjects with poor adherence were more frequently inpatients and showed higher current substance use, a greater number of previous hospitalizations, and more severe scores at psychopathological assessment compared with patients with positive adherence. Poor adherence was associated with symptom severity and increased rates of relapses and rehospitalizations. In addition, substance use appears to be an unfavorable transdiagnostic factor for treatment adherence.

Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology.

OBJECTIVE: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment. METHODS: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth. RESULTS: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6. CONCLUSIONS: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.

Partial Response to Antidepressant Treatment: The Role of Nutraceutical Compounds.

Objective: Depression represents one of the most severe psychiatric disorders, characterized by low mood episodes, as well as loss of interest. Major Depressive Episodes (MDE) treatment relies primarily on monoaminergic prescriptions. However, although the presence of many antidepressant medications, their efficacy is still partial. A promising intervention to improve antidepressant treatment may be the use of adjunctive nutraceuticals. Aim of the present study was to assess the efficacy of a N-Acetyl-cysteine, S-Adenosyl-L-Methionine and Folic acid's combination for the treatment of depressive symptoms in a sample of MDE patients. Method: Fifty outpatients with a MDE diagnosis in the context of different psychiatric disorders such as Major Depression, Bipolar Disorder, Anxiety disorders, and Personality disorders were recruited. The sample was divided into different groups based on the nutraceutical administration: a) concurrently with an AD (starter group); b) add-on to an already prescribed treatment; c) single treatment. Results: A significant reduction of CGI-Severity and Improvement scores from baseline to the end of treatment was found. Moreover, the starter group showed a significantly greater CGI-Improvement score compared to the other groups. Ninety-four percent of patients did not show any side effects. Conclusions: The present study showed promising results for the use of nutraceuticals in the add-on treatment of MDE. Those compounds may be considered a versatile, tolerable, and effective add-on treatment for the reduction of depressive symptoms impact and for improving the functioning of patients affected by MDE.

Staging models applied in a sample of patients with bipolar disorder: Results from a retrospective cohort study.

BACKGROUND: Bipolar Disorder (BD) is a life-long illness with compelling evidence of progression. Although different staging models have been proposed to evaluate its course, clinical data remain limited. The aim of the present study was to retrospectively assess applicability of available staging approaches and their pattern of progression in a sample of bipolar patients. METHODS: In a naturalistic sample of 100 BD patients, retrospective assessment of clinical stages was performed at four time points over 10 years, according to four staging models. Staging progression with potential associations between stages and unfavourable illness characteristics were analyzed. RESULTS: A pattern of stage worsening emerged for each model, with a significant increase at every time point. Greater stage increases emerged in patients with lower educational level, age at first elevated episode ≤35 years, duration of illness ≤25 years, and duration of untreated illness ≤5 years. Lower stage values were associated with BD II, no psychiatric hospitalization, depressive onset and predominant polarity, ≤three lifetime episodes, age at first mood stabilizer >40 years, duration of illness ≤25 years, and engaged/employed status. Higher stage values were associated with lower age at first elevated episode and mood stabilizing treatment instead. LIMITATIONS: Naturalistic and retrospective design, recruitment at a 2nd level specialistic clinic. CONCLUSIONS: Reported findings support the progressive nature of BD and the application of staging models for early intervention, suggesting a conceptualization of a standardized approach to better characterize patients, predict their clinical course, and deliver tailored treatment options.

Intensive Neurofeedback Protocol: An Alpha Training to Improve Sleep Quality and Stress Modulation in Health Care Professionals During the Covid-19 Pandemic. A Pilot Study.

Objective: health care workers (HCWs) represent a vulnerable group in the COVID-19 pandemic, given the exposure to greater risk and higher levels of work-related stress. Neurofeedback (NF) has shown to be effective in the treatment of stress-related symptoms. We aimed to assess the effectiveness of an alpha-increase NF protocol for the treatment of acute stress symptoms in HCWs exposed to the COVID-19 pandemic. Method: eighteen medical doctors on duty during the COVID-19 health emergency underwent an intensive NF alpha-increase protocol. The mean alpha wave values were recorded at the beginning (T0) and at the last day of stimulation (T1). Rapid Stress Assessment: Italian version; Copenhagen Burnout Inventory (CBI); Pittsburgh Sleep Quality Index (PSQI), and Brief-COPE were administered as psychometric assessment. Results: a significant increase in alpha wave values and a significant reduction of the PSQI scores from T0 to T1 were found. Conclusions: NF alpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement, and safety in a pilot sample of HCWs.

The Role of Lifestyle on Adherence to Treatment in a Sample of Patients with Unipolar and Bipolar Depression.

Introduction: Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence. The aim of the present study is to assess potential differences in terms of clinical and lifestyle features related to adherence to treatment in a sample of patients with unipolar and bipolar depression. Methods: One hundred and eight patients with a diagnosis of unipolar or bipolar depressive episode were recruited from January 2021 to October 2022. Adherence to psychopharmacological treatment was assessed using the clinician rating scale. Descriptive and association analyses were performed to compare subgroups based on adherence to treatment. Results: Lower levels of adherence to treatment were associated with fewer years of education, work impairment, manic prevalent polarity lifetime, and greater comorbidity with alcohol and drug abuse. The majority of patients with positive adherence did not report any hospitalization and involuntary commitment lifetime. Conclusions: Patients with a positive treatment adherence showed significant differences in terms of lifestyle and clinical features compared to non-adherent patients. Our results may help to identify patients more likely to have poor medication adherence, which seem to lead to a worse disease course and quality of life.

First vs second wave of COVID-19 pandemic in patients with obsessive compulsive disorder: A multicentre report from tertiary clinics in Northern Italy.

INTRODUCTION: Among patients with mental illness, those with obsessive compulsive disorder (OCD) showed a significant clinical worsening by the COVID-19 pandemic. The effects of the COVID-19 pandemic on OCD have been shown to worsen symptoms severity, with serious clinical consequences. However, the persistence of COVID-19 pandemic in OCD patients has been poorly investigated. The purpose of the present study was to assess the impact of the second wave of the COVID-19 pandemic in a sample of OCD patients and to compare the results with those obtained during the first wave on the same OCD sample. METHODS: 116 OCD outpatients attending three OCD tertiary clinics in Northern Italy and previously included in a report on the impact of COVID-19, were followed-up in order to investigate sociodemographic and clinical features. Appropriate statistical analyses for categorical and continuous variables were conducted. RESULTS: The 43 OCD patients with a clinical worsening (OW) reported a significant development of new obsessions/compulsions and the recurrence of past OC symptoms, higher rates of psychiatric comorbidities and sleep disturbances compared to patients without symptom worsening. Moreover, an increase in avoidance behaviors, suicidal ideation, Internet checking for reassurance, and job difficulties emerged in OW patients. Also, lower rates of pharmacological stability, and higher rates of therapy adjustment were observed. In terms of sex differences, males showed higher rates of past obsessions occurrence, while females showed a rise in Internet checking behaviors. When comparing OW patients between the first and the second wave, the latter showed significantly higher rates of past obsession occurrence and lower rates of pharmacological stability. Moreover, patients with OW showed a significantly older age during the second wave. CONCLUSION: The persistence of the COVID-19 pandemic showed a globally impaired clinical picture in the analyzed OCD sample. A further worsening between the two waves timepoints emerged, mainly involving older patients with OCD. The concordance between our results and those existing in literature highlights the importance of an accurate long-term monitoring of OCD patients in light of COVID-19 pandemic persistence.

Clinical characteristics and comorbidity associated with female gender in obsessive-compulsive disorder.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a heterogeneous condition characterized by largely variable phenotypic expressions. Previous findings suggested that gender may be a relevant factor in mediating this heterogeneity. The present study aimed at exploring gender differences in a large clinical sample of Italian OCD patients. METHODS: Socio-demographic and clinical variables of a sample of 229 consecutive OCD outpatients were included in a common database. Patients were assessed through structured clinical interviews, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale. RESULTS: Female OCD patients were more likely than males to have lifetime psychiatric comorbidities (72.6% vs 56.9%; p < 0.05), poly-comorbidities being twice as high compared to males. The female group also showed a significant later onset of symptoms (63.7% vs 44.8%; p < 0.005) and a higher age at first treatment (30.98 ± 13.1 years vs 27.81 ± 11.3; p < 0.005). Moreover, the female subgroup presented higher rates of cleaning and washing compulsions, compared to the male subgroup (28.7% vs 12.6% in the male group; p < 0.005). CONCLUSIONS: The current study supports the notion that OCD in female gender is frequently a comorbid condition with other specific clinical characteristics compared to male patients. These findings should be considered in epidemiologic and therapeutic perspectives.

What Happened to Patients With Obsessive Compulsive Disorder During the COVID-19 Pandemic? A Multicentre Report From Tertiary Clinics in Northern Italy.

After the outbreak of Coronavirus disease was declared a pandemic by the World Health Organization, this resulted in extraordinary public health measures to control the infection, such as entire countries being placed under quarantine. The psychopathological consequences of the pandemic and quarantine were anticipated to be of particular relevance, especially in patients with psychiatric disorders such as Obsessive Compulsive Disorder (OCD). Aim of the present report was to describe the impact of COVID-19 pandemics within a sample of Italian patients affected by OCD. Sociodemographic and clinical variables of a sample of 123 OCD outpatients, currently attending three OCD tertiary clinics in Northern Italy, were assessed through telephone and in-person interviews. Patients showing a clinical worsening of OCD represented more than one third of the sample and reported a significant emergence of new obsessions and compulsions phenotypes along with a significant exacerbation of past ones. Moreover, they were more frequently found to experience suicidal ideation, increased Internet checking, sleep disturbances, avoidance behaviors, and work difficulties. A significantly increased need of therapy adjustment and family accommodation was also observed. Further research is warranted to clarify the potential risk and related consequences of the current COVID-19 pandemic on OCD patients.

Peripheral Biomarkers in DSM-5 Anxiety Disorders: An Updated Overview.

Anxiety disorders are prevalent and highly disabling mental disorders. In recent years, intensive efforts focused on the search for potential neuroimaging, genetic, and peripheral biomarkers in order to better understand the pathophysiology of these disorders, support their diagnosis, and characterize the treatment response. Of note, peripheral blood biomarkers, as surrogates for the central nervous system, represent a promising instrument to characterize psychiatric disorders, although their role has not been extensively applied to clinical practice. In this report, the state of the art on peripheral biomarkers of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) Anxiety Disorders is presented, in order to examine their role in the pathogenesis of these conditions and their potential application for diagnosis and treatment. Available data on the cerebrospinal fluid and blood-based biomarkers related to neurotransmitters, neuropeptides, the hypothalamic-pituitary-adrenal axis, neurotrophic factors, and the inflammation and immune system are reviewed. Despite the wide scientific literature and the promising results in the field, only a few of the proposed peripheral biomarkers have been defined as a specific diagnostic instrument or have been identified as a guide in the treatment response to DSM-5 Anxiety Disorders. Therefore, further investigations are needed to provide new biological insights into the pathogenesis of anxiety disorders, to help in their diagnosis, and to tailor a treatment.