Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders

In recent years, an increasing number of neuroimaging studies have sought to identify the brain anomalies associated with mood and anxiety disorders. The results of such studies could have significant implications for the development of novel treatments for these disorders. A challenge currently facing the field is to assimilate the large and growing corpus of imaging data to inform a systems-level model of the neural circuitry underlying the disorders. One prominent theoretical perspective highlights the top-down inhibition of amygdala by ventromedial prefrontal cortex (vmPFC) as a crucial neural mechanism that may be defective in certain mood and anxiety disorders, such as major depression and post-traumatic stress disorder. In this article, we provide a critical review of animal and human data related to this model. In particular, we emphasize the considerable body of research that challenges the veracity (or at least completeness) of the predominant model. We propose a framework for constructing a more comprehensive model of vmPFC function, with the goal of fostering further progress in understanding the neuropathophysiological basis of mood and anxiety disorders.     

Darwinian models of depression: a review of evolutionary accounts of mood and mood disorders

Over the last ten years, there has been increased interest in the evolutionary origins of depressive phenomena. The current article provides a review of the major schools of thought that have emerged in this area. First, we consider important Darwinian explanations of depressed mood, including an integrative social risk hypothesis recently proposed by the authors. According to the social risk hypothesis, depression represents an adaptive response to the perceived threat of exclusion from important social relationships that, over the course of evolution, have been critical to maintaining an individual's fitness prospects. We argue, moreover, that in the ancestral environment, depression minimized the likelihood of exclusion by inducing: (i) cognitive hypersensitivity to indicators of social risk/threat; (ii) signaling behaviours that reduce social threat and elicit social support; and (iii) a generalized reduction in an individual's propensity to engage in risky, appetitive behaviours. Neurobiological support for this argument is also provided. Finally, we review three models that endeavour to explain the relationship between the adaptations that underlie depressed mood and clinically significant, depressed states, followed by a consideration of the merits of each.     

Reliability of DSM and empirically derived prototype diagnosis for mood,anxiety and personality disorders

BackgroundProminent psychiatric diagnostic systems such as the DSM-IV and ICD-10 have shown low reliability in clinical practice. An alternative approach to classification of psychiatric disorders is prototype matching. In the current study, we examined reliability of assessing mood, anxiety and personality disorders using a multi-method multi informant approach. More specifically, we examined diagnosis made by treating clinician and independent expert clinical interviewer, using three different diagnostic systems (DSM symptom count, DSM-IV prototype diagnosis and empirically derived prototype diagnosis).MethodsA convenience sample of clinicians (N = 80) and patients (N = 170) from eight community mental health clinics in Israel participated in the study.ResultsOur findings show fair to excellent interrater reliability for prototype dimensional diagnostic systems (ranged from 0.40 to 0.79) for most mood and anxiety disorders examined. Overall, dimensional diagnostic systems, yielded better interrater reliability for mood, anxiety and personality disorders, as compared with categorical diagnosis. There were no significant differences between dimensional systems.ConclusionsOur findings provide further support to the advantages of dimensional over categorical models in increasing reliability.     

Managing mood disorders and comorbid personality disorders

PURPOSE OF REVIEW: To examine the influence of personality disorder comorbidity on the general treatment of mood disorders. RECENT FINDINGS: Personality disorders generally have a negative influence on outcome of mood disorders, both unipolar and bipolar. When the personality features are addressed, however, the outcome is less negative. Recent studies suggest a special role for psychological and educational therapies in the treatment of these comorbid disorders. SUMMARY: The assessment of, and attention to, the management of personality disorder as well as concurrent mood disorder may improve outcome.     

The prevalence of atypical features across mood,anxiety, and personality disorders

This study examines and compares the prevalence rates of the atypical features subtype across each of the major mood, anxiety, and personality disorders (PDs). It also evaluates the impact that comorbid anxiety and PDs have on the likelihood that depressed patients will present with atypical symptoms. Eleven hundred thirty psychiatric outpatients were evaluated for the presence of atypical symptoms. All axis I diagnoses were made using the Structured Clinical Interview for DSM-IV (SCID). PDs were assessed in a subset of 530 patients using the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). From a sample of 579 patients diagnosed with a current major depressive disorder, 22.5% met criteria for the atypical subtype. Prevalence rates were similar in bipolar and unipolar patients, although the pattern of symptoms was distinct. Prevalence rates were lower in patients with dysthymic disorder (12.5%), adjustment disorder with depressed mood (9.4%), and depression not otherwise specified (NOS) (7.9%). When major depression existed in the presence of a comorbid anxiety disorder, the likelihood of presenting with atypical features doubled. Nine percent of the patients diagnosed with an anxiety disorder (without a comorbid depressive disorder) met criteria for atypical features. Two of the four atypical symptoms, leaden paralysis and rejection sensitivity, were found to be especially prominent in nondepressed anxiety disorder patients. Of the 10 PDs listed in DSM-IV, only avoidant PD was associated with the atypical features subtype. In large part, this was accounted for by the high rate of rejection sensitivity in these patients. In conclusion, as many as one quarter of depressed patients who present for outpatient psychiatric treatment meet criteria for the atypical features subtype. There appears to be a strong association between anxiety and atypical depression, but the exact nature of this relationship needs to be further elucidated. It is unclear whether personality pathology is independently associated with the atypical features subtype.     

Comorbidity of mood and anxiety disorders

This article reviews data on the prevalence of panic, social phobia, generalized anxiety, and posttraumatic stress disorder, and research documenting the comorbidity of these disorders with major depression (MDD). These anxiety disorders are frequently comorbid with MDD, and 50-60% of individuals with MDD report a lifetime history of one or more of these anxiety disorders. The anxiety disorders are also highly correlated with one another, and approximately one-quarter to one-half of individuals with each of the anxiety disorders report a lifetime history of an alcohol or substance use disorder. Anxiety disorders rarely exist in isolation, with several studies reporting that over 90% of individuals with anxiety disorders have a lifetime history of other psychiatric problems. Implications for research are discussed, including the potential benefit of using combined categorical and dimensional rating scale approaches in future genetic, biochemical, neuroimaging, and treatment studies. The clinical implications of the findings are also discussed, and the results of recent clinical trials summarized. Available data suggests selective serotonin reuptake inhibitors are the first-line pharmacological treatment for these disorders, and that newer serotonin and norepinephrine reuptake inhibitors show significant promise, especially for comorbid cases. Comorbidity among depression and anxiety disorders is associated with greater symptom severity, and a considerably higher incidence of suicidality. Increased public awareness about these disorders and the availability of effective treatments is sorely needed.     

The temporal course of anxiety sensitivity in outpatients with anxiety and mood disorders: relationships with behavioral inhibition and depression

The present study evaluated the temporal course of three dimensions of anxiety sensitivity (AS; concerns over physical symptoms, mental incapacitation, and social embarrassment) and their relationships with behavioral inhibition (BI) and depression (DEP) in 606 outpatients with anxiety and mood disorders. A semi-structured interview and self-report questionnaires were administered on three occasions over a two-year period. All three constructs decreased over the study period and AS temporally functioned more similar to DEP than BI. Cross-sectional and temporal correlations supported the discriminant validity of AS from BI. As expected, initial levels of BI predicted less improvement in all AS dimensions. In contrast, higher initial levels of mental incapacitation AS were associated with greater improvement in DEP. Our results are discussed in regard to the measurement of AS in clinical samples, conceptualizations of AS as a lower-order vulnerability, and prognostic implications of directional paths between BI and AS and AS and DEP.     

DSM-III personality disorders among patients with major depression, anxiety disorders, and mixed conditions

Of 298 mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age, a group of patients having either pure major depression, major depression in combination with anxiety disorders, or pure anxiety disorders was extracted. The anxiety disorders were further differentiated in panic and nonpanic anxiety disorders. The groups were compared as to differences in frequency of personality disorders assessed by means of the Structured Interview for DSM-III Personality Disorders. The mixed major depression/anxiety disorder group appeared to be the most deviant with more severe personality disorders such as paranoid and borderline in addition to avoidant and dependent personality disorder. The differentiation between panic and nonpanic anxiety showed that it was patients with nonpanic anxiety features in addition to major depression who had this higher frequency of personality disorders. These findings imply that it is important to distinguish between major depression cases with and without anxiety disorders both in forthcoming research and in clinical practice.     

Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders

The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.     

Sequential treatment of mood and anxiety disorders

OBJECTIVE: Administration of treatments in a sequential order is a common practice in clinical medicine, but has received insufficient attention in psychiatry. The aim of this review was to survey the literature concerned with a sequential use of pharmacotherapy and psychotherapy in mood and anxiety disturbances. DATA SOURCES AND STUDY SELECTION: A review of the clinical trials in which treatment components were used in a sequential order (i.e., pharmacotherapy followed by psychotherapy, psychotherapy followed by pharmacotherapy, one drug treatment following another, or one psychotherapeutic technique following another) was performed. Studies were identified by using MEDLINE (English language articles published from 1967 to March 2005; keywords: sequential treatment, drugs and psychotherapy, combined treatment related to depressive disorder, bipolar disorder, depression, mania, anxiety disorders, panic disorder, social phobia, obsessive-compulsive disorder, generalized anxiety disorder, and posttraumatic stress disorder) and a manual search of the literature and Index Medicus for the years 1960 to 2005. DATA SYNTHESIS: In unipolar recurrent depression, the sequential use of pharmacotherapy was found to reduce relapse rate. In bipolar disorder, the use of psychotherapeutic strategies in patients who were already undergoing treatment with mood stabilizers was also found to yield clinical benefits. In anxiety disorders, the sequential use of pharmacotherapy and psychotherapy was not found to improve long-term outcome. CONCLUSION: The sequential treatment of mood and anxiety disorders does not fall within the realm of maintenance strategies. It is an intensive, 2-stage approach, which is based on the fact that one course of treatment with a specific treatment (whether pharmacotherapy or psychotherapy) is unlikely to entail solution to the complex array of symptoms of patients with mood and anxiety disorders. The sequential model introduces a conceptual shift in current assessment methods.     

Anxiety,personality and anxiety disorders

The roles of trait anxiety, locus of control and defense style in the genesis and maintenance of anxiety are described. A model of the genetic and environmental determinants of these three measures is presented. The contributions that such vulnerability factors make to anxiety and the anxiety disorders is estimated and discussed in relation to the issue of co-moribidity and the general neurotic syndrome. Some evidence is presented about the specificity of the various anxiety disorders even though other conditions may have co-occurred, for they are often found to be secondary to the index condition. Such a two-factor theory of neurosis, one that implies both a general vulnerability due to high trait anxiety and poor coping, and an independent but specific vulnerability to a particular disorder, will make definitive research very complex. Aetiological factors or treatments that are believed to be specifically associated with only one disorder will have to be shown to be associated with that disorder alone and not with other anxiety disorders or with asymptomatic normals high on these general vulnerability factors.     

Barriers to help-seeking, detection, and adequate treatment for anxiety and mood disorders: implications for health care policy

Recently, the focus of health policies and initiatives has been directed toward mental health. More precisely, depressive and anxiety disorders have received particular attention because of their disabling outcomes and prevalence among most populations. Despite this increased interest, numerous issues regarding patients' willingness to seek treatment and the adequate recognition and treatment of these disorders by clinicians remain to be addressed. This article considers the factors that influence patients and physicians in their reticence to acknowledge and adequately treat depression and anxiety disorders. It also reviews the impact of society and the media, together with other factors relating to health care organization and administration that affect the treatment of depression and anxiety. In view of the multifaceted challenge involved, efforts to achieve a consensus in determining treatment for those with depressive and anxiety disorders are essential. A consensus will require easy, measurable, and reliable disability indicators; evidence that treatment of patients with varying levels of need is cost effective; and that persons who most need and would benefit from care can be reliably identified among the highly prevalent population of persons with more transient symptoms. Governments and other policymakers should be encouraged to provide appropriate coverage for access to primary and secondary care, the treatments required, and sufficient resources so that care is available when necessary. An important aspect of the challenge is to incorporate these efforts within the realistic constraints of primary care.     

Parenting stress and postpartum depression/anxiety in mothers with personality disorders: indications for differential intervention priorities

To date, parenting stress has rarely been examined in clinical samples of mothers with postpartum comorbid Axis-I disorders and Axis-II personality disorders (PD). Previous research has shown important links between maternal psychopathology and the development of child psychopathology. For these reasons, a clinical sample (N = 54) of mothers with various PD and comorbid depression/anxiety disorders were compared in this study. The clinical sample was divided into three groups based on PD: without PD, other PD, and borderline PD (BPD), and then matched according to depression/anxiety diagnoses and age. Parenting stress index (PSI, Abidin, 1995) scores were compared between these subsamples and to a nonclinical control group. No significant differences were found between mothers with various PD on global PSI scores. However, further examination of the PSI subscale scores revealed that PD were linked to an impaired sense of competence and positive reinforcement in relation to parenting. Compared to mothers with other PD, mothers with BPD had significantly more interpersonal issues. Compared to the nonclinical controls, clinically referred mothers had significantly higher PSI global and subscale scores, with notable PD-specific exceptions. These results illustrate the need for more differentiated treatment options for mothers with postpartum depression and/or anxiety disorders with PD to prevent later development of psychopathology in children of these mothers.     

Premorbid personality aspects in mood and schizophrenic disorders

This study examines premorbid personality traits from a self-reported and family-reported perspective on a group of unipolar major depression (n = 27), bipolar (n = 21), and schizophrenic (n = 16) recovered inpatients, and a control group (n = 21). Using the Munich Personality Test (MP-T Scales) of von Zerssen for self-reporting and family-reporting personality traits, and the Kischkel scale for the measurement of “intolerance of ambiguity,” we found more “rigidity,” less “esoteric tendencies,” and more “intolerance of ambiguity” patng unipolar depressive patients. Schizophrenic patients showed more esoteric tendencies and less “extraversion.” Results confirm the hypothesis supported by many authors regarding a particular personality structure in unipolar major depression characterized by ridigity and ambiguity intolerance. This personality pattern for unipolar depressives seems to be different from the depressive personality disorder proposed by DSM-IV. Schizophrenic individuals differ by means of their self- and family-reported extraversion. Clinical and theoretical implications of these findings are discussed.