Is the female preponderance in major depression secondary to a gender difference in specific anxiety disorders?

BACKGROUND: While a female preponderance in unipolar depression is a consistent finding in community-based studies, determinants remain speculative. This study aimed to examine whether a female preponderance in certain anxiety disorders drives a gender difference in depression. METHOD: The relevant data from the National Comorbidity Study (NCS) are analysed. RESULTS: We observed a biphasic pattern in the emergence of a female preponderance in the depressive and anxiety disorders, with an initial pre-pubertal or early adolescent onset, and after attenuation in early to middle adulthood, re-emergence in mid- to late-adulthood. Analyses focused on determinants of the initial female preponderance. Female gender, presence of an anxiety disorder and variable ages of onset in the anxiety disorder all contributed to the increased chance of an initial depressive episode. Some specificity in linking the onset of depressive temporally in early adolescence with two anxiety disorders was demonstrated, specifically generalized anxiety disorder and panic disorder. CONCLUSIONS: The separate anxiety disorders and their age of onset had variable links with depression, but female gender remained a significant predictor of depression after accounting for the effects of prior anxiety.     

The influence of anxiety as a risk to early onset major depression.

OBJECTIVE: we seek to identify and quantify any risk provided by several expressions of "anxiety" to major depression overall, and to separate melancholic and non-melancholic sub-types. METHOD: a sample of 269 patients with a current major depressive episode was assessed for rates of separate formalised anxiety disorders, both for lifetime and prior to the initial depressive episode. We also sought for evidence of familial anxiety and, early childhood expression of anxiety forerunners, measured both state and trait anxiety levels as well as anxiety at a "personality" level, and assessed use of anxiolytic medications. Depressive sub-typing was undertaken using DSM-IV criteria, while "early onset" (EO) depression was defined as an initial onset at 25 years or less, and subsequently re-examined with a cut-off age of 20 years or less. RESULTS: overall. 42% of our sample were assigned as having EO depression, with there being a higher representation of non-melancholic than melancholic EO subjects (i.e., 51% vs. 29%), arguing for sub-type status being respected in the analyses. For both melancholic and non-melancholic subjects two trait anxiety items ("tense"; "keyed up/on edge") were over-represented, suggesting that such a tense anxiety style may provide an antecedent risk to depression (of either sub-type) or be a consequence of depression. Specificity was most evident in the non-melancholic sub-sample, where EO depression was associated with a family history of anxiety, early childhood expressions of anxiety and with two lifetime anxiety disorders (social phobia and obsessive-compulsive disorder). Broadly similar results were returned when "EO" definition was reduced to 20 years or less. CONCLUSIONS: our study is consistent with previous research in identifying anxiety in the form of social inhibition or social avoidance as being particularly likely to precede and perhaps be a conduit to early onset non-melancholic major depression. This conclusion both sharpens risk factor research and indicates an important fulcrum that could be used to assist primary prevention of the depressive disorders.     

Major depression in patients with panic disorder: factors associated with course and recurrence

The relationship between anxiety and depressive disorders has been the subject of considerable interest and controversy. In this study, the occurrence and course of affective illness was systematically examined in 63 patients meeting DSM-III-R criteria for panic disorder. Forty (63%) of the patients had experienced at least one major depressive episode. Of these, 13 (32.5%) experienced their first depressive episode prior to the onset of panic disorder, 15 (37.5%) experienced their first depressive episode after the onset of panic disorder, and in 12 (30.0%) the onset of the disorders was concurrent. Patients with agoraphobia had comparable rates of depression (68%) to patients without agoraphobia (53%, P = NS), and they had similar temporal patterns of depressive illness. Comorbidity with social phobia was associated with an increased longitudinal likelihood of major depression compared to patients without this comorbid diagnosis (P less than 0.05). Patients with longer duration of illness, early onset depression, melancholic depression, or family histories of anxiety or depression had an increased likelihood of having experienced recurrent depression. These findings are discussed in the context of current theories regarding the development of affective illness in patients with anxiety disorders.     

Obsessive-compulsive disorder and separation anxiety co-morbidity in early onset panic disorder.

BACKGROUND: This study was undertaken to examine the relationship between anxiety co-morbidity and age of onset of panic disorder. METHODS: Age of onset of panic disorder and co-morbid anxiety disorders were assessed among 201 panic disorder probands with childhood separation anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, social phobia and specific phobia as part of a clinician-administered lifetime diagnostic interview. A generalized linear model was used to test the association between each anxiety co-morbidity and age of panic disorder onset while simultaneously controlling for the potential confounding effects of sociodemographic characteristics and other psychiatric co-morbidity. RESULTS: Earlier onset of panic disorder was found in patients with co-morbid obsessive-compulsive disorder, obsessive-compulsive symptoms and separation anxiety disorder, but not simple phobia or social phobia. Patients with both childhood separation anxiety disorder and obsessive-compulsive disorder had an even earlier panic onset than those with either childhood separation anxiety disorder or obsessive-compulsive disorder. CONCLUSIONS: The association between anxiety co-morbidity and earlier onset of panic disorder is specific to obsessive-compulsive disorder and childhood separation anxiety disorder.     

Anxiety disorders comorbidity in bipolar I, bipolar II and unipolar major depression: results from a population-based study in Hungary

BACKGROUND: The aim of this study was to analyze the lifetime comorbidity between DSM-III-R anxiety disorders in separate subgroups of patients with major depression, bipolar II and bipolar I disorder in a community sample of a Hungarian population. METHODS: Randomly selected subjects (aged between 18 and 64 years, N=2953) were interviewed by the Diagnostic Interview Schedule (DIS) which generated DSM-III-R diagnoses. RESULTS: The prevalence of generalized anxiety disorder, agoraphobia and simple phobia was the highest among bipolar II patients (20.8, 37.5 and 16.7%, respectively), social phobia was most prevalent in (nonbipolar) major depression (17.6%), while the rate of panic disorder was the same in the (nonbipolar) major depressive and bipolar II subgroups (12.4 and 12.5%, respectively). Bipolar I patients showed a relatively low rate of comorbidity. CONCLUSIONS: The findings support previous results on the particularly high rate of lifetime comorbidity between anxiety disorders and unipolar major depression and particularly bipolar II illness. LIMITATIONS: Underestimation of the prevalence of bipolar II disorder by the diagnostic methodology used, resulting in a small number of bipolar II cases, lack of analysis of data by gender, no data on obsessive-compulsive disorder.     

Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D

BACKGROUND: Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features. OBJECTIVE: The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns. METHOD: Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/ Somatization factor score of > or =7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C30). RESULTS: The prevalence of anxious depression in this population was 46 %. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features. CONCLUSION: This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression).     

Bipolar-panic comorbidity in the general population: prevalence and associated morbidity

BACKGROUND: The goal of this study was to determine the prevalence, psychiatric comorbidity, panic symptomotology and physical morbidity associated with the co-occurrence of bipolar disorder and panic attacks in the general population. METHOD: Data were drawn from the National Comorbidity Survey, a community-based household sample (n=8098) representative of the US adult population aged 15-54. F tests were used to determine differences in sociodemographic characteristics, panic symptoms, physical and psychiatric morbidity between individuals with bipolar disorder with and without co-occurring panic attacks (lifetime). Multiple logistic regression analyses were used to identify sociodemographic and psychiatric correlates of the co-occurrence of bipolar disorder and panic attacks. RESULT: The co-occurrence of bipolar disorder and panic attacks was associated with earlier onset of panic attack [17.1 (8.7) years vs. 22.0 (10.3) years, F=8.3, df=1, 429, P=0.004] and significantly greater panic symptomotology (P<0.0001). Comorbid substance dependence [OR=5.8 (2.6, 13.0)], specific phobia [OR=3.3 (1.4, 7.6)], and GAD [OR=2.9 (1.3, 6.8)] were each independent correlates of the co-occurrence bipolar disorder and panic attacks. CONCLUSIONS: These findings are consistent with, and extend, results from clinical studies showing that panic attacks are not uncommon, and are associated with significantly elevated rates of comorbid psychopathology, among individuals with bipolar disorder in the general population. Future studies that examine the relationship between panic attacks and bipolar disorder using a longitudinal design may be helpful in improving our understanding of the mechanism of this association.     

The temporal relationship between anxiety disorders and (hypo)mania: a retrospective examination of 63 panic, social phobic and obsessive-compulsive patients with comorbid bipolar disorder

BACKGROUND: The relationship between anxiety and depressive disorders has been conventionally limited to unipolar depression. Recent studies from both clinical and epidemiologic samples have revealed intriguing associations between anxiety and bipolar (mainly bipolar II) disorders. The present report examines the temporal sequence of hypomania to panic (PD), obsessive-compulsive (OCD) and social phobic (SP) disorders. METHODS: Specialty-trained clinicians retrospectively evaluated the foregoing relationships in 63 patients meeting the DSM-III-R diagnosis for PD, OCD and SP with lifetime comorbidity with bipolar disorders (87% bipolar II). Structured interviews were used. RESULTS: In nearly all cases, SP chronologically preceded hypomanic episodes and disappeared when the latter episodes supervened. By contrast, PD and OCD symptomatology, even when preceding hypomanic episodes, often persisted during such episodes; more provocatively, nearly a third of all onsets of panic attacks were during hypomania. LIMITATIONS: Assessing temporal relationships between hypomania and specific anxiety disorders on a retrospective basis is, at best, of unknown reliability. The related difficulty of ascertaining the extent to which past antidepressant treatment of anxiety disorders could explain the anxiety-bipolar II comorbidity represents another major limitation. CONCLUSIONS: Different temporal relationships characterized the occurrence of hypomania in individual anxiety disorder subtypes. Some anxiety disorders (notably SP, and to some extent OCD) seem to lie on a broad affective continuum of inhibitory restraint vs. disinhibited hypomania. By contrast, and more tentatively, PD in the context of bipolar disorder, might be a reflection of a dysphoric manic or mixed hypomanic symptomatology. The foregoing suggestions do not even begin to exhaust the realm of possibilities. The pattern of complex relationships among these disorders would certainly require better designed prospective observations.     

Severe melancholic depression is more vulnerable than non-melancholic depression to minor precipitating life events

BACKGROUND: The present study examines the moderating role of global depression severity on the relation of melancholic versus non-melancholic depression to severe and non-severe levels of stress. METHOD: A community sample of 50 women with unipolar major depressive disorder, of which 54% met Research Diagnostic Criteria for melancholic depression, were interviewed regarding stressful life events experienced prior to onset. Events were coded as severe or non-severe based on the rigorous Bedford College contextual rating system. RESULTS: Greater severity of depression was related to a higher likelihood of a severely stressful event prior to onset only for women with non-melancholic major depression. By contrast, greater severity of depression was related to a higher likelihood of a non-severe, more minor, stressful event prior to onset only for women with melancholic major depression. LIMITATIONS: The present study was limited by its use of a female volunteer sample, which might not be entirely representative of the population of individuals with major depression. In addition, the study employed a cross-sectional design, which limits conclusions relating to the causal relation of stress to melancholic versus non-melancholic depression. CONCLUSIONS: Far from being autonomous of stress, individuals with severe melancholic depression may be especially sensitive to stress, such that their episodes are influenced by more minor stressors than those of individuals with non-melancholic depression.     

Anxiety disorders and the onset of depression among adults in the community

OBJECTIVE: To determine the association between anxiety disorders, panic attack and the risk of major depression among adults in the community. METHOD: Data were drawn from the Epidemiologic Catchment Area Program survey waves 1 (N = 20291) and 2 (N = 15849). Multivariate logistic regression analyses were used to determine the risk of incident major depression at 12-month follow-up (wave 2) associated with each anxiety disorder and panic attacks assessed at wave 1, adjusting for differences in sociodemographic characteristics, and then controlling simultaneously for all anxiety disorders, and other psychiatric co-morbidity. RESULTS: Specific phobia (OR = 1.7 (1.6, 1.8)), agoraphobia (OR = 2.3 (2.2, 2.5)), obsessive-compulsive disorder (OR = 5.4 (5.0, 5.8)) and panic attack (OR = 1.9 (1.8, 2.1)) each made an independent contribution to the risk of major depression, which persisted after adjusting simultaneously for sociodemographic differences and other psychiatric co-morbidity. CONCLUSIONS: Each anxiety disorder and panic attacks appear to confer an independent risk for the onset of major depression within 12-months among adults in the community. Understanding the key role played by anxiety in depression onset is needed for prevention strategies.     

Assessment of depressive symptom severity among patients with co-occurring bipolar disorder and substance dependence

BACKGROUND: We examined a modified version of the Hamilton Depression Rating Scale (HDRS) among treatment-seeking patients with co-occurring bipolar disorder and substance dependence in order to elucidate key features of depression in this specific population of patients. METHODS: Patients with current bipolar disorder and substance dependence who were prescribed mood stabilizers (n=105) completed a 27-item version of the HDRS that was subjected to item and principal components analyses. Preliminary validity analysis consisted of comparing the derived total and component scores to the depressed mood indicators from the Addiction Severity Index (ASI). RESULTS: Eleven items representing two related components labeled "melancholia" and "anxiety" were retained. The 11-item HDRS total and component scores were higher for those who reported serious depression, serious anxiety, cognitive problems, and suicidal ideation on the ASI than for those who did not report these problems. LIMITATIONS: We conducted the analyses with a relatively small sample of patients who were primarily white and were diagnosed with bipolar I disorder, thus limiting the generalizability of findings. Moreover, we obtained limited data regarding construct validity of the 11-item scale. CONCLUSIONS: Our psychometric evaluation of the HDRS led us to retain 11 items representing primarily melancholic and neurovegetative symptoms of depression. These findings suggest that sample-specific item characteristics of the HDRS need to be evaluated prior to using this scale to assess depressive symptom severity among patients with complex diagnostic and treatment characteristics.     

Depressions in Alzheimer's disease

The aim of this work was to study clinical and pathogenetic aspects of depression associated with Alzheimer disease (AD) in 65 patients. Depressive symptoms are shown to frequently occur in all types of the disease and at all stages of its therapy. A variety of syndromic variants of depression are identified in the structure of dementia: anxiety (35.4%), apathetic (29.2%), delusional (16.9%), hypochondriac (10.8%), melancholic (7.7%). Situation-reactive, endoreactive, and endogenous types of depression were distinguished depending on its pathogenetic mechanisms. Great variety of clinical and psychopathological manifestations and mechanisms of depressive pathology in AD suggests its heterogeneous character.     

Understanding the link between anxiety symptoms and suicidal ideation and behaviors in outpatients with bipolar disorder

BACKGROUND: Prior studies suggest an association between anxiety comorbidity and suicidal ideation and behaviors in bipolar disorder. However, the nature of this association remains unclear. METHODS: We examined a range of anxiety symptoms, including panic, phobic avoidance, anxiety sensitivity, worry and fear of negative evaluation, in 98 patients with bipolar disorder. We predicted that each anxiety dimension would be linked to greater suicidal ideation and behavior as measured by Linehan's Suicide Behaviors Questionnaire (SBQ), greater depressive rumination, and poorer emotional processing and expression. RESULTS: Each anxiety dimension except fear of negative evaluation was associated with greater SBQ score, greater rumination, and lower levels of emotional processing in univariate analyses. Depressive rumination was a significant predictor of higher SBQ scores in a stepwise multivariate model controlling for age, gender, bipolar subtype, and bipolar recovery status; the association between the anxiety symptom dimensions and SBQ score was found to be redundant with depressive rumination. Emotional processing emerged as protective against suicidal ideation and behaviors in men only, while emotional expression was a significant predictor of lower SBQ scores for women and for the full sample; however, emotional expression was not significantly correlated with anxiety symptoms. Confirmatory analyses examining only those in recovery or recovered (n=68) indicated that the link between rumination and suicidality was not explained by depression. LIMITATIONS: Interpretation is limited by the cross-sectional study design. CONCLUSIONS: These findings indicate that increased ruminations may mediate the association between anxiety and suicidal ideation/behavior. In men, lower emotional processing may also play a role in this relationship.     

The relationship between agoraphobia symptoms and panic disorder in a non-clinical sample of adolescents

BACKGROUND: The purpose of this study was to evaluate the clinical correlates of agoraphobic fear and avoidance and panic disorder in a non-clinical sample of adolescents. METHOD: In a sample of 2365 high school students, combined data from a questionnaire and a structured clinical interview were used to classify subjects with agoraphobic fear and avoidance. Panic symptoms, major depression, childhood separation anxiety disorder, anxiety sensitivity and negative affectivity were also assessed. RESULTS: Fifteen subjects met study criteria for agoraphobic fear and avoidance in the past year. Only three (20%) of those with agoraphobia symptoms reported histories of panic attacks and there was no overlap between those with agoraphobic fear and avoidance and the 12 subjects who met DSM-III-R criteria for panic disorder. However, subjects with agoraphobia symptoms and those with panic disorder reported similar levels of anxiety sensitivity and negative affectivity. Childhood separation anxiety disorder was more common among those with agoraphobic fear and avoidance compared to those without. CONCLUSION: Agoraphobic avoidance is rare in non-clinical samples of adolescents and usually not associated with panic attacks. However, adolescents with agoraphobia symptoms and those with panic disorder have similar clinical correlates consistent with a panic/agoraphobia spectrum model.     

Bipolar mood disorders among Polish psychiatric outpatients treated for major depression

BACKGROUND: Significant proportion of patients treated for depression may have various types of bipolar mood disorders. The aim of the study was to assess the frequency of bipolar disorders among outpatients having at least one major depressive episode, treated by 96 psychiatrists, representing all regions of Poland. METHODS: The study included 880 patients (237 male, 643 female), identified to following diagnostic categories: bipolar I, bipolar II, bipolar spectrum disorder and major depressive disorder. RESULTS: Bipolar mood disorders were found in 61.2% of patients studied, bipolar I more frequent in men and bipolar II in women, and bipolar spectrum in 12% of patients. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Patients with bipolar mood disorders compared to major depressive disorder had significantly more frequent family history of bipolar disorder, premorbid hyper- or cyclothymic personality, early onset of depression, symptoms of hypersomnia and hyperphagia, psychotic depression, post-partum depression, and treatment-resistant depression. Bipolar spectrum patients had most clinical features similar to classic types of bipolar disorders. LIMITATIONS: Neither structured interview for family history, nor formal criteria for a number of clinical manifestations were used. The population treated by psychiatrists may not be representative and present a subgroup with more severe mood disorders. CONCLUSIONS: Bipolar mood disorders may be very prevalent among depressive outpatients treated by psychiatrists in Poland, which is confirmed by the results of recent studies. Bipolar patients (including bipolar spectrum) significantly differ from major depressive disorder as to numerous clinical features related mostly to depressive episode.     

The HPA axis and perinatal depression: a hypothesis

Summary Episodes of depression and anxiety are as common during pregnancy as postpartum. Some start in pregnancy and resolve postpartum, others are triggered by parturition and some are maintained throughout. In order to determine any biological basis it is important to delineate these different subtypes. During pregnancy, as well as the rise in plasma oestrogen and progesterone there is a very large increase in plasma corticotropin releasing hormone (CRH), and an increase in cortisol. The latter reaches levels found in Cushing’s syndrome and major melancholic depression. Levels of all these hormones drop rapidly on parturition. We here suggest that the symptoms of antenatal and postnatal depression may be different, and linked in part with differences in the function of the hypothalamic pituitary adrenal (HPA) axis. There are two subtypes of major depression, melancholic and atypical, with some differences in symptom profile, and these subtypes are associated with opposite changes in the HPA axis. Antenatal depression may be more melancholic and associated with the raised cortisol of pregnancy, whereas postnatal depression may be more atypical, triggered by cortisol withdrawal and associated with reduced cortisol levels. There is evidence that after delivery some women experience mild bipolar II depression, and others experience post traumatic stress disorder. Both of these are associated with atypical depression. It may also be that some women are genetically predisposed to depression of the melancholic type and some to depression of the atypical type. These women may be more or less vulnerable to depression at the different stages of the perinatal period.     

The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention

BACKGROUND: Previous reports have shown a significant relationship between suicide ideation and mixed depression. The aim of this study was to explore the prevalence and clinical characteristics of mixed depression among non-violent suicide attempters. METHODS: Using a structured interview (modified Mini International Neuropsychiatric Interview) and assessing all the symptoms of 16 psychiatric diagnoses, the authors examined 100 consecutive nonviolent suicide attempters (aged 18-65) within 24 h after their attempts. Mixed depression was defined as a major depressive episode (MDE)/dysthymic disorder plus 3 or more co-occurring hypomanic symptoms, according to the definition validated by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2003a. Delineating depressive mixed states: Their therapeutic significance. Clin. Approaches Bipolar Disord. 2, 41-47, Akiskal, H.S., Benazzi, F., 2003b. Family history validation of the bipolar nature of depressive mixed states. J. Affect. Disord. 73, 113-122.]. RESULTS: Current mixed depression was present in 63.0% in the total sample, and in 70.8% among the 89 depressive suicide attempters. Irritability, distractibility and psychomotor agitation were present in more than 90% of the subjects with mixed depression. The rate of mixed depression was significantly higher among bipolar than non-bipolar depressive suicide attempters (90% vs. 62%). Patients with mixed depression had the following concurrent disorders: bipolar disorders 41.0%, panic disorder 30.0%, generalized anxiety disorder 89.0%, alcohol abuse/dependence 56.0%, and substance abuse 27.0%. Mixed depression versus non-mixed depression had the following significant associations (odds ratio=OR): females 2.4, bipolar II disorder 9.3, generalized anxiety disorder 41.3, irritability 101.6 and psychomotor agitation 61.1. LIMITATIONS: The study didn't include suicide attempters with very high risk of fatality. CONCLUSIONS: The important new finding of this study is the very high prevalence of mixed depression among depressed suicide attempters. The rates of mixed depression among bipolar and non-bipolar depressive suicide attempters were much higher than previously reported among nonsuicidal bipolar II and unipolar depressive outpatients, suggesting that suicide attempters come mainly from mixed depressives with predominantly bipolar II base. Irritability and psychomotor agitation were the strongest predictors of suicide attempt. From a public health standpoint, our data highlight the necessity of detecting and treating mixed (bipolar) depression in the prevention of suicidal behaviour.     

The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues

BACKGROUND: Although symptoms of anxiety as well as anxiety disorders commonly occur in patients with bipolar disorder, the pathophysiologic, theoretical, and clinical significance of their co-occurrence has not been well studied. METHODS: The epidemiological and clinical studies that have assessed the overlap of bipolar and anxiety disorders are reviewed, with focus on panic disorder and obsessive-compulsive disorder (OCD), and to a lesser extent, social phobia and post-traumatic stress disorder. Potential neural mechanism and treatment response data are also reviewed. RESULTS: A growing number of epidemiological studies have found that bipolar disorder significantly co-occurs with anxiety disorders at rates that are higher than those in the general population. Clinical studies have also demonstrated high comorbidity between bipolar disorder and panic disorder, OCD, social phobia, and post-traumatic stress disorder. Psychobiological mechanisms that may account for these high comorbidity rates likely involve a complicated interplay among various neurotransmitter systems, particularly norepinephrine, dopamine, gamma-aminobutyric acid (GABA), and serotonin. The second-messenger system constituent, inositol, may also be involved. Little controlled data are available regarding the treatment of bipolar disorder complicated by an anxiety disorder. However, adequate mood stabilization should be achieved before antidepressants are used to treat residual anxiety symptoms so as to minimize antidepressant-induced mania or cycling. Moreover, preliminary data suggesting that certain antimanic agents may have anxiolytic properties (e.g. valproate and possibly antipsychotics), and that some anxiolytics may not induce mania (e.g. gabapentin and benzodiazepines other than alprazolam) indicate that these agents may be particularly useful for anxious bipolar patients. CONCLUSIONS: Comorbid anxiety symptoms and disorders must be considered when diagnosing and treating patients with bipolar disorder. Conversely, patients presenting with anxiety disorders must be assessed for comorbid mood disorders, including bipolar disorder. Pathophysiological, theoretical, and clinical implications of the overlap of bipolar and anxiety disorders are discussed.     

Carbon dioxide provocation of anxiety and respiratory response in bipolar disorder

BACKGROUND: Frequent bipolar/panic comorbidity implies bipolar individuals may experience CO2-provoked anxiety and changes in respiratory patterns similar to those experienced by individuals with panic disorder. METHODS: 16 euthymic bipolar individuals breathed air and air combined with 5% CO2 for 15 min each. Respiratory and subjective anxiety measures were collected. RESULTS: On CO2 subjects were more anxious and breathed more deeply and rapidly than with air; the degree of increase in anxiety attributable to CO2 was directly correlated with the degree of increase in minute ventilation. Five individuals were assessed as having a panic attack. Panic response to CO2 was predicted by the degree of anxiety experienced with air alone. CONCLUSIONS: Comparison with the results of similar panic studies shows bipolar disorder is associated with enhanced respiratory response to CO2. Hypersensitivity to CO2 among bipolar individuals suggests a possible pathological mechanism common to both bipolar and panic disorders. These preliminary data support the expanded application of CO2 challenges in bipolar subjects.     

The DSM IV diagnoses of melancholic and atypical depression in pregnancy

Atypical and melancholic subtypes of depression based on the Diagnostic and Statistical Manual (DSM) IV are important concepts, especially for biological psychiatry. The aim of this study was to determine whether the symptoms used for the diagnoses of atypical and melancholic depression can distinguish these subtypes during pregnancy. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all DSM IV symptoms of melancholic and atypical depression with depressed and non-depressed women in pregnancy. A Swiss cohort of 449 women was interviewed. Four diagnostic groups were compared: women with melancholic, atypical or non specified depression, and those without depression. Seventeen per cent of the cohort met SCID criteria for a depressive episode of depression at least once in pregnancy, with melancholic depression 2.4%, atypical depression 4.4% and non specified depression 10.2%. Many of the symptoms used to distinguish atypical and melancholic depression did not discriminate between these groups during pregnancy. However some, such as mood reactivity, distinct quality of mood and sleep pattern, did discriminate. Differential diagnosis between melancholic and atypical depression in pregnancy needs to be based on pregnancy specific definitions. The possible therapeutic consequences and the neurobiological basis for these findings warrant further research.