Pharmacogenomics and therapeutic prospects in dementia

OBJECTIVE: To describe the prevalence and correlates of post-traumatic stress disorder (PTSD), depressive and anxiety disorders, or any other mental disorder among adult victims treated in a hospital at different points in time after the 11 March 2004 terrorist attacks in Madrid. DESIGN, SETTING, AND PARTICIPANTS: A random sample of 56 individuals injured in the attacks was interviewed in person at one, six, and twelve months after the attacks. MAIN OUTCOME MEASURES: Current DSM-IV mental disorders: depressive disorders and anxiety disorders (PTSD, generalised anxiety, agoraphobia, social phobia, and panic disorder) were assessed with the Spanish version of the MINI (Mini International Neuropsychiatric Interview), a structured, lay-administered psychiatric interview. RESULTS: PTSD was the most prevalent psychiatric disorder (35.7% at month 1, 34.1% at month 6, and 28.6% at month 12), followed by major depression (28.6%, 22.7%, and 28.6%, respectively). Others relevant conditions were suicide risk, generalised anxiety disorder (GAD), agoraphobia, and panic disorder. No significant differences in the prevalence of the disorders were found between the different assessment times. Patients with a psychiatric history prior to 11 March had a higher prevalence of PTSD, major depression, GAD, and panic disorder at month 1. Females had higher prevalence of PTSD, agoraphobia, and panic disorder at month 1. The only predictive factor for PTSD at month 12 was PTSD at month 6 (OR = 14.007). The only predictive factor for major depression at month 12 was major depression at month 6 (OR = 15.847). CONCLUSION: The prevalence of PTSD and major depression was high and remained stable between month 1, month 6, and month 12. The only predictive factor for PTSD at month 12 was PTSD at month 6.     

Psychiatric morbidity and comorbidity following accidental man-made traumatic events: incidence and risk factors

The aims of this study were to examine the incidence and risk factors of major depression, bipolar disorder, psychoactive substance use, psychotic and anxiety disorders in relation to post-traumatic stress disorders (PTSD) in a study group exposed to two different traumatic events, i. e. 128 fire and 55 motor vehicle accident victims. Data have been collected 7–9 months after the traumatic event. The diagnosis of axis-I diagnoses, other than PTSD, was made according to DSM-III-R criteria using the Structured Interview according to the DSN-III-R. The incidence of new-onset major depression was 13.4%, generalised anxiety disorder (GAD) 12.6%, agoraphobia 10.2% and psychoactive substance use disorders 6%. Simple phobia, panic disorder and obsessive compulsive disorder had a much lower incidence (< 2.0%). Fifty-one percent of the victims with PTSD had one or more addition axis-I diagnoses, major depression (26.2%), agoraphobia (21.0%) and generalised anxiety disorder (24.6%) being the most common. Physical injury was the single best predictor for major depression. The best predictors for the development of new-onset anxiety disorders, other than PTSD, were: type and horror of the trauma, the extent of physical injury, the loss of control during the traumatic event, contextual stimuli, younger age and female sex. In conclusion: comorbid disorders, such as depression, GAD and agoraphobia, commonly occur within the first few months after man-made accidental traumata. Trauma variables, which are known to be related to the development of PTSD, are also related to the occurrence of these comorbid disorders. Received: 2 July 1999 / Accepted: 27 January 2000     

Lifetime and 12-month prevalence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition disorders among older African Americans: findings from the National Survey of American Life.

OBJECTIVE: The purpose of this study was to estimate lifetime and 12-month prevalence of 13 psychiatric disorders for older African Americans. METHODS: Data are from the older African American subsample of the National Survey of American Life. Selected measures of lifetime and 12-month Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) psychiatric disorders were examined (i.e., panic disorder, agoraphobia, social phobia, generalized anxiety disorder, obsessive compulsive disorder, posttraumatic stress disorder (PTSD), major depressive disorder, dysthymia, bipolar I and II disorders, alcohol abuse/dependence, and drug abuse/dependence). RESULTS: Twenty-three percent of older African Americans reported at least one lifetime disorder and 8.54% reported at least one 12-month disorder. Alcohol abuse, PTSD, and major depression were the most prevalent lifetime disorders. The most prevalent 12-month disorders were PTSD, major depression, and social phobia. Age, sex, education, and region were significantly associated with the odds of having a lifetime disorder. CONCLUSION: This is the first study of prevalence rates of serious mental disorders for older African Americans based on a national sample. Demographic correlates of the prevalence of disorders are discussed with an emphasis on age and regional differences.     

Anxiety disorders in major depression

The prevalence and clinical impact of anxiety disorder comorbidity in major depression were studied in 255 depressed adult outpatients consecutively enrolled in our Depression Research Program. Comorbid anxiety disorder diagnoses were present in 50.6% of these patients and included social phobia (27.0%), simple phobia (16.9%), panic disorder (14.5%), generalized anxiety disorder ([GAD] 10.6%), obsessive-compulsive disorder ([OCD] 6.3%), and agoraphobia (5.5%). While both social phobia and generalized anxiety preceded the first episode of major depression in 65% and 63% of cases, respectively, panic disorder (21.6%) and agoraphobia (14.3%) were much less likely to precede the first episode of major depression than to emerge subsequently. Although comorbid groups were not distinguished by depression, anxiety, hostility, or somatic symptom scores at the time of study presentation, patients with comorbid anxiety disorders tended to be younger during the index episode and to have an earlier onset of the major depressive disorder (MDD) than patients with major depression alone. Our results support the distinction between anxiety symptoms secondary to depression and anxiety disorders comorbid with major depression, and provide further evidence for different temporal relationships with major depression among the several comorbid anxiety disorders.     

Clinical characteristics and treatment outcomes of patients with major depressive disorder and comorbid anxiety disorders - results from a European multicenter study

This naturalistic European multicenter study aimed to elucidate the association between major depressive disorder (MDD) and comorbid anxiety disorders. Demographic and clinical information of 1346 MDD patients were compared between those with and without concurrent anxiety disorders. The association between explanatory variables and the presence of comorbid anxiety disorders was examined using binary logistic regression analyses. 286 (21.2%) of the participants exhibited comorbid anxiety disorders, 10.8% generalized anxiety disorder (GAD), 8.3% panic disorder, 8.1% agoraphobia, and 3.3% social phobia. MDD patients with comorbid anxiety disorders were characterized by younger age (social phobia), outpatient status (agoraphobia), suicide risk (any anxiety disorder, panic disorder, agoraphobia, social phobia), higher depressive symptom severity (GAD), polypsychopharmacy (panic disorder, agoraphobia), and a higher proportion receiving augmentation treatment with benzodiazepines (any anxiety disorder, GAD, panic disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder). The results in terms of treatment response were conflicting (better response for panic disorder and poorer for GAD). The logistic regression analyses revealed younger age (any anxiety disorder, social phobia), outpatient status (agoraphobia), suicide risk (agoraphobia), severe depressive symptoms (any anxiety disorder, GAD, social phobia), poorer treatment response (GAD), and increased administration of benzodiazepines (any anxiety disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder) to be associated with comorbid anxiety disorders. Our findings suggest that the various anxiety disorders subtypes display divergent clinical characteristics and are associated with different variables. Especially comorbid GAD appears to be characterized by high symptom severity and poor treatment response.     

Management of anxiety in late life

Epidemiologic data are used as a framework to discuss the pharmacologic and cognitive-behavioral management of anxiety disorders in late life. Generalized anxiety disorder (GAD) and phobias account for most cases of anxiety in late life. The high level of comorbidity between GAD and major depression, and the observation that the anxiety usually arises secondarily to the depression, suggests that antidepressant medication should be the primary pharmacologic treatment for many older people with GAD. Most individuals with late-onset agoraphobia do not have a history of panic attacks and the illness often starts after a traumatic event. Exposure therapy is the treatment of choice for agoraphobia without panic. It is uncommon for obsessive-compulsive disorder (OCD) and panic disorder to start for the first time in old age, but these disorders can persist from younger years into late life. Case reports and uncontrolled case series suggest that elderly people with OCD or panic disorder can benefit from pharmacologic and cognitive-behavioral treatments that are known to be effective in younger patients. However, it is not known whether the rate of response among elderly patients is adversely affected by the chronicity of these disorders. The prevalence and incidence of post-traumatic stress disorder in late life are not known. Uncontrolled data support the use of selective serotonin reuptake inhibitors in war veterans with chronic symptoms of post-traumatic stress disorder; other treatments for this condition await evaluation in the elderly.     

The effect of somatic symptom attribution on the prevalence rate of depression and anxiety among nursing home patients

The validity of diagnostic psychiatric instruments for depression and anxiety disorders may be compromised among patients with complex physical illness and disability. The objective of this study was to determine the effect on the prevalence rate of depression and anxiety in a nursing home population of attributing somatic symptoms of depression and anxiety to either somatic or psychiatric disorder. Symptoms of major depression (MD), generalized anxiety disorder (GAD) and panic disorder (PD) were measured using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Somatic symptoms of MD, GAD and PD were attributed to somatic causes when the interviewer was not sure about a psychiatric cause. To analyse the effect of this attribution on the prevalence rate of MD, GAD and PD, a sensitivity analysis was undertaken in which symptoms that were attributed to somatic causes were recoded as symptoms attributed to psychiatric disorder. Prevalence rates of MD, GAD and PD were calculated before and after recoding. The prevalence of MD after recoding rose from 7.5% to 8.1%. The prevalence of GAD did not change. The prevalence of PD rose from 1.5% to 1.8%. Attribution of somatic symptoms to either somatic or psychiatric disorder when the interviewer was not sure about a psychiatric cause of the somatic symptoms had only a very modest effect on the prevalence rate of major depression, generalized anxiety disorder and panic disorder in a nursing home population.     

On the threshold of disorder: a study of the impact of the DSM-IV clinical significance criterion on diagnosing depressive and anxiety disorders in clinical practice

BACKGROUND: Two recent reanalyses of epidemiologic studies found that adding a clinical significance criterion reduced disorder prevalence. Patients presenting for clinical care are usually distressed or impaired by their symptoms; thus, the DSM-IV clinical significance criterion might have little impact on diagnosis in clinical practice. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examine the impact of the DSM-IV clinical significance criterion on diagnostic frequencies of depressive and anxiety disorders in psychiatric outpatients. METHOD: 1500 psychiatric outpatients were evaluated with the Structured Clinical Interview for DSM-IV. We determined the percentage of patients who met symptom criteria but did not meet the DSM-IV clinical significance criterion for major depressive disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social phobia, specific phobia, panic disorder, and obsessive-compulsive disorder. RESULTS: No patient who met the symptom criteria for current major depressive disorder or PTSD failed to meet the clinical significance criterion. Less than 2% of patients meeting the symptom criteria for current GAD did not meet the clinical significance criterion. There was variability among the remaining anxiety disorders in the percentage of symptomatic patients who met the clinical significance criterion. CONCLUSION: In psychiatric patients, the clinical significance criterion had little impact on diagnosing major depressive disorder, GAD, and PTSD, disorders that are defined, in part, by disruptions of daily regulatory domains such as sleep, appetite, energy, and concentration. In contrast, the clinical significance criterion had a greater impact in determining whether phobic fears, obsessive thoughts, and panic attacks were sufficiently distressing or impairing to qualify for disorder status.     

Induced abortion and anxiety, mood, and substance abuse disorders: Isolating the effects of abortion in the national comorbidity survey

The purpose of this study was to examine associations between abortion history and a wide range of anxiety (panic disorder, panic attacks, PTSD, Agoraphobia), mood (bipolar disorder, mania, major depression), and substance abuse disorders (alcohol and drug abuse and dependence) using a nationally representative US sample, the national comorbidity survey. Abortion was found to be related to an increased risk for a variety of mental health problems (panic attacks, panic disorder, agoraphobia, PTSD, bipolar disorder, major depression with and without hierarchy), and substance abuse disorders after statistical controls were instituted for a wide range of personal, situational, and demographic variables. Calculation of population attributable risks indicated that abortion was implicated in between 4.3% and 16.6% of the incidence of these disorders. Future research is needed to identify mediating mechanisms linking abortion to various disorders and to understand individual difference factors associated with vulnerability to developing a particular mental health problem after abortion.     

Agoraphobia with panic attacks. Development, diagnostic stability, and course of illness

A structured psychiatric interview was used to examine the symptom history of 55 patients meeting DSM-III criteria for agoraphobia with panic attacks and five patients meeting DSM-III criteria for panic disorder. Anticipatory anxiety and generalized anxiety occurred in over 80% of the patients, and these anxiety states together with panic attacks and phobic avoidances had courses that were chronic and unremitting. Major depression occurred in 70% of the patients and had an episodic course that differentiated it from the anxiety states. Other frequently reported disorders were childhood separation disorder (18%), alcoholism (17%), and obsessive compulsive disorder (17%). An initial nonspontaneous first panic attack and separation anxiety was associated with earlier onset and longer duration of agoraphobia and panic disorder. An inaccurate cognitive appraisal of the initial panic attack frequently led to the rapid development of subsequent agoraphobia. Caffeine consumption exacerbated anxiety in 54% of the patients and triggered panic attacks in 17%. Fifty-one percent of female agoraphobics experienced premenstrual exacerbation of anxiety symptoms.     

Longitudinal study of the influence of life events and personality status on diagnostic change in three neurotic disorders

It has been known for many years that diagnosis within the neurotic spectrum of disorders is temporally unstable and also that life events can be major precipitants of change in symptoms. Reasons for this instability could include inherent inadequacy of current diagnostic practice, the influence of life events as an agent of diagnostic shift, and an innate course of disorder with features dependent on the stage at which disorder presents (e.g., development of panic to agoraphobia). These possibilities were examined in a prospective study that was initially a randomised controlled trial. Two hundred ten patients recruited from primary care psychiatric clinics with DSM-III diagnosed dysthymic, generalised anxiety, and panic disorders were randomly allocated to either drug treatment (mainly antidepressants), cognitive-behaviour therapy, or self-help therapy over a 2 year period, irrespective of original diagnosis. Life events were recorded by using a standard procedure over the period 6 months before starting treatment and at five occasions over 2 years; 181 (86%) of the patients had follow-up data and 76% maintained compliance with the original treatment allocated over the 2 years; and 155 of the 181 patients (86%) had at least one diagnostic change in this period. There was no difference in the number of diagnostic changes between the three original diagnostic groups, but dysthymic disorder changed more frequently to major depressive episode than did GAD or panic disorder (20; 11; 12) (%) and panic disorder changed more frequently to agoraphobia (with or without panic) than did dysthymia or GAD (18; 8; 6) (%). There was no relationship between loss events and depressive diagnoses or between addition events and anxiety diagnoses, but greater numbers of conflict events were associated with diagnostic change. More life events were associated with the flamboyant and dependent personality disorders, reinforcing other evidence that many life events are internally generated by personality characteristics and cannot be regarded as truly independent.     

Anxiety disorders in women.

Women have higher overall prevalence rates for anxiety disorders than men. Women are also much more likely than men to meet lifetime criteria for each of the specific anxiety disorders: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), simple phobia, panic disorder, and agoraphobia. Considerable evidence suggests that anxiety disorders remain underrecognized and undertreated despite their association with increased morbidity and severe functional impairment. Increasing evidence suggests that the onset, presentation, clinical course, and treatment response of anxiety disorders in women are often distinct from that associated with men. In addition, female reproductive hormone cycle events appear to have a significant influence on anxiety disorder onset, course, and risk of comorbid conditions throughout a woman's life. Further investigations concerning the unique features present in women with anxiety disorders are needed and may represent the best strategy to increase identification and optimize treatment interventions for women afflicted with these long-neglected psychiatric disorders.     

A cluster analysis of early onset in common anxiety disorders

Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and generalised anxiety disorder, using cluster analysis with data gathered in the general population. Resulting cut-off ages for early onset were ≤22 (social phobia), ≤31 (panic disorder), ≤21 (agoraphobia), and ≤27 (generalised anxiety disorder). Comparison of psychiatric comorbidity and general wellbeing between subjects with early and late onset in the general population and an outpatient cohort, demonstrated that among outpatients anxiety comorbidity was more common in early onset agoraphobia, but also that anxiety- as well as mood comorbidity were more common in late onset social phobia. A major limitation was the retrospective assessment of onset. Our results encourage future studies into correlates of early onset of psychiatric disorders.     

Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression

The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder.     

Psychiatric disorders in asthmatic outpatients

It has been reported that the lifetime prevalence of panic disorder in patients with pulmonary disease is higher than epidemiologic estimates of population prevalence. We evaluated the frequency of anxiety disorders in 86 subjects from the Outpatient Asthma Clinic. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview 4.4 Version (MINI). Forty-five asthmatic patients (52.3%) reported at least one current anxiety disorder. The frequency of panic disorder with or without agoraphobia was 13.9% (n=12) and that of agoraphobia without panic disorder was 26.8% (n=23). Social anxiety and generalized anxiety disorders occurred in 9.3% (n=8) and 24.4% (n=21) of the sample, respectively. Twenty-nine patients (33.7%) reported a major depressive episode. The psychiatric morbidity of the sample was 61.6% (n=53). Our results tend to support the high morbidity of anxiety disorders, particularly panic/agoraphobic spectrum disorders, in asthmatic outpatients.     

Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States

Estimates of 12‐month and lifetime prevalence and of lifetime morbid risk (LMR) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) anxiety and mood disorders are presented based on US epidemiological surveys among people aged 13+. The presentation is designed for use in the upcoming DSM‐5 manual to provide more coherent estimates than would otherwise be available. Prevalence estimates are presented for the age groups proposed by DSM‐5 workgroups as the most useful to consider for policy planning purposes. The LMR/12‐month prevalence estimates ranked by frequency are as follows: major depressive episode: 29.9%/8.6%; specific phobia: 18.4/12.1%; social phobia: 13.0/7.4%; post‐traumatic stress disorder: 10.1/3.7%; generalized anxiety disorder: 9.0/2.0%; separation anxiety disorder: 8.7/1.2%; panic disorder: 6.8%/2.4%; bipolar disorder: 4.1/1.8%; agoraphobia: 3.7/1.7%; obsessive‐compulsive disorder: 2.7/1.2. Four broad patterns of results are most noteworthy: first, that the most common (lifetime prevalence/morbid risk) lifetime anxiety‐mood disorders in the United States are major depression (16.6/29.9%), specific phobia (15.6/18.4%), and social phobia (10.7/13.0%) and the least common are agoraphobia (2.5/3.7%) and obsessive‐compulsive disorder (2.3/2.7%); second, that the anxiety‐mood disorders with the earlier median ages‐of‐onset are phobias and separation anxiety disorder (ages 15–17) and those with the latest are panic disorder, major depression, and generalized anxiety disorder (ages 23–30); third, that LMR is considerably higher than lifetime prevalence for most anxiety‐mood disorders, although the magnitude of this difference is much higher for disorders with later than earlier ages‐of‐onset; and fourth, that the ratio of 12‐month to lifetime prevalence, roughly characterizing persistence, varies meaningfully in ways consistent with independent evidence about differential persistence of these disorders. Copyright © 2012 John Wiley & Sons, Ltd.     

Comparing primary and secondary generalized anxiety disorder in a long-term naturalistic study of anxiety disorders.

This study explores the potential differences in comorbidity and course between primary generalized anxiety disorder (GAD), which develops before other anxiety disorders, and secondary GAD. As part of the Harvard/Brown Anxiety Research Project (HARP), a naturalistic, long-term, longitudinal study of 711 subjects from a variety of clinic settings with DSM III-R defined anxiety disorders, 210 subjects with GAD were identified. Of these, 78 (37%) had primary GAD, and 84 (40%) had secondary GAD; of the remainder, 28 (13%) had no other anxiety disorder and 20 (10%) developed GAD within a month of another anxiety disorder and were excluded from the analysis. All subjects were comorbid for at least one other anxiety disorder. Primary GAD subjects were more likely to be in episode at intake (90% vs. 77%, P = .04) and less likely than secondary GAD subjects to have current or past agoraphobia without panic disorder (3% vs. 11%, P = .04), social phobia (19% v. 52%, P = .001), simple phobia (14% v. 30%, P = .02), or post traumatic stress disorder (5% vs. 20%, P = .01). Subjects with primary GAD were also less likely to have current or past alcohol use disorders (17% vs. 37%, P = .004) or major depressive disorder (60% vs. 76%, P = .03). There were no significant differences in either treatment approaches or remission rates for primary compared to secondary GAD. Whether GAD first occurs before or after another anxiety disorder, it is similar in terms of prevalence, treatment, and course. The only significant differences between primary and secondary GAD lie in the rates of comorbidity of both other anxiety disorders and non-anxiety disorders, including major depression and substance abuse. These results support the concept of GAD as a valid, separate and distinct entity, whether it occurs primarily or secondarily.     

Depression and anxiety disorders in parents and children. Results from the Yale family study

The children (aged 6 to 17 years) of probands with primary major depression, with and without various anxiety disorders, were compared with the children of a matched normal control group. The results from the study of these young children parallel our previous findings among the adult first-degree relatives of these probands. Depression in the proband increased the risk of depression in the children. Depression plus panic disorder or agoraphobia in the proband conferred an additional risk of depression and of an anxiety disorder in the children. Panic disorder in the parents conferred more than a threefold increased risk of separation anxiety in the children. Other factors that increased the risk to children were degree of familial loading for psychiatric illness, parental assortative mating, and parental recurrent depression. The findings suggest a relationship between depression and some of the anxiety disorders, and between adult panic disorder and agoraphobia and transmission of anxiety disorders to children.     

Panic attacks. A review of treatments and pathogenesis

In the psychiatric literature, panic attacks have been considered as part of the clinical manifestations of anxiety neurosis, agoraphobia, functional cardiovascular disturbances, and the phobic depersonalization syndrome. Even though recurrent spontaneous panic attacks are described in these entities, the importance ascribed to them has been minor one. Therefore, panic attacks are poorly understood from a psycho-physio pathological point of view. In the past years, new trends in the nosology of psychiatric disorders have grouped the recurrent spontaneous panic attacks under the heading "panic disorder and agoraphobia with panic attacks." In this view, we present the results of the controlled pharmacological trials on patients complaining of panic attacks. Some relationships between panic attacks, panic disorder, and agoraphobia are discussed.     

The prevalence of depression and anxiety disorders in indigenous people of the Americas: A systematic review and meta-analysis

Indigenous populations are considered at higher risk of psychiatric disorder but many studies do not include direct comparisons with similar non-Indigenous controls. We undertook a meta-analysis of studies that compared the prevalence of depression and anxiety disorders in Indigenous populations in the Americas with those of non-Indigenous groups with similar socio-demographic features (Registration number: CRD42015025854). A systematic search of PubMed, Medline, PsycInfo, PsycArticles, ScienceDirect, EMBASE, and article bibliographies was performed. We included comparisons of lifetime rates and prevalence of up to 12 months. We found 19 studies (n = 250, 959) from Latin America, Canada and the US. There were no differences between Indigenous and similar non-Indigenous groups in the 12-month prevalence of depressive, generalised anxiety and panic disorders. However, Indigenous people were at greater risk of PTSD. For lifetime prevalence, rates of generalised anxiety, panic and all the depressive disorders were significantly lower in Indigenous participants, whilst PTSD (on adjusted analyses) and social phobia were significantly higher. Results were similar for sub-analyses of Latin America, Canada and the US, and sensitivity analyses by study quality or setting (e.g. health, community etc.). Risk factors for psychiatric illness may therefore be a complex interaction of biological, educational, economic and socio-cultural factors that may vary between disorders. Accordingly, interventions should reflect that the association between disadvantage and psychiatric illness is rarely due to one factor. However, it is also possible that assessment tools don't accurately measure psychiatric symptoms in Indigenous populations and that further cross-cultural validation of diagnostic instruments may be needed too.