Incidence and predictors of relapse during continuation treatment of major depression with SSRI, interpersonal psychotherapy, or their combination.

BACKGROUND: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. METHODS: The study sample includes 225 patients who entered the 6-month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. RESULTS: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. CONCLUSIONS: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience.

From the third month of pregnancy to 1 year postpartum. Prevalence, incidence, recurrence, and new onset of depression. Results from the perinatal depression-research & screening unit study.

OBJECTIVE: Perinatal depression is a particular challenge to clinicians, and its prevalence estimates are difficult to compare across studies. Furthermore, to our knowledge, there are no studies that systematically assessed the incidence of perinatal depression. The aim of this study is to estimate the prevalence, incidence, recurrence, and new onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, minor and major depression (mMD) in an unselected population of women recruited at the third month of pregnancy and followed up until the 12th month postpartum. METHOD: One thousand sixty-six pregnant women were recruited. Minor and major depression was assessed in a naturalistic, longitudinal study. The Edinburgh Postnatal Depression Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders were administered at different time points during pregnancy and in the postpartum period. RESULTS: The period prevalence of mMD was 12.4% in pregnancy and 9.6% in the postpartum period. The cumulative incidence of mMD in pregnancy and in the postpartum period was 2.2% and 6.8%, respectively. Thirty-two (7.3%) women had their first episode in the perinatal period: 1.6% had a new onset of depression during pregnancy, 5.7% in the postpartum period. CONCLUSIONS: Our postpartum prevalence figures, which are lower than those reported in the literature, may reflect treatment during the study, suggesting that casting a multiprofessional network around women in need of support may be potentially useful for reducing the effects of this disorder on the mother and the newborn child. Furthermore, our results indicate that women with a history of depression have a 2-fold risk of developing mMD in the perinatal period.

Reductions in platelet 18-kDa translocator protein density are associated with adult separation anxiety in patients with bipolar disorder.

BACKGROUND: Recent studies indicate that adult separation anxiety disorder is a discrete diagnostic entity and worthy of attention. Previously, we found a significant association between platelet expression of the 18-kDa translocator protein (TSPO) and adult separation anxiety in patients with panic disorder or major depression. The aim of this study was to explore whether adult separation anxiety might be a factor differentiating TSPO expression in a sample of patients with bipolar disorder. METHODS: The equilibrium binding parameters of the specific TSPO ligand [(3)H]PK 11195 were estimated on the platelet membranes of 24 adult outpatients with a DSM-IV diagnosis of bipolar disorder (with or without separation anxiety disorder) and 14 healthy controls. Patients were assessed by SCID-I, HAM-D, YMRS, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-Report Checklist (ASA-27). RESULTS: A significant reduction in mean platelet TSPO density was found in bipolar patients with respect to controls. However, the lower density was only evident in the subgroup of bipolar patients who also fulfilled DSM-IV criteria for adult separation anxiety disorder. Individual TSPO density values correlated significantly and negatively with both SCI-SAS-A and ASA-27 total scores. CONCLUSIONS: TSPO expression may be a useful biological marker of adult separation anxiety co-occurring with other anxiety and mood disorders, including bipolar disorder.

Neuroleptic malignant syndrome: further lessons from a case report.

BACKGROUND: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. OBJECTIVE: The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. METHOD: Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. RESULTS: Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. CONCLUSION: This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS.

Distinguishing affective depersonalization from anhedonia in major depression and bipolar disorder.

BACKGROUND: Affective depersonalization has received limited attention in the literature, although its conceptualization may have implications in terms of identification of clinical endophenotypes of mood disorders. Thus, this study aims to test the hypothesis that anhedonia and affective depersonalization represent 2 distinct psychopathological dimensions and to investigate their clinical correlates in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Using a data pool of 258 patients with mood and anxiety disorders, an item response theory-based factor analysis approach was carried out on 16 items derived from 2 clinical instruments developed in the Spectrum Project (the Structured Clinical Interview for Mood Spectrum and the Structured Clinical Interview for Derealization-Depersonalization Spectrum). Clinical correlates of these psychometrically derived dimensions were subsequently investigated in patients with BD or MDD. RESULTS: Using an item response theory-based factor analysis, a 2-factor solution was identified, accounting overall for the 47.0% of the variance. Patients with BD showed statistically significant higher affective depersonalization factor scores than those with MDD (Z = 2.215, P = .027), whereas there was no between-groups difference in anhedonia scores (Z = 0.825 P = .411). In patients with BD, age of onset of the disease correlated with affective depersonalization factor scores (rho = -0.330, P = .001) but not with anhedonia factor scores (rho = -0.097, P = .361). CONCLUSIONS: Affective depersonalization and anhedonia seem to be 2 distinct psychopathological dimensions, although closely related, bearing the opportunity to identify patients with a specific profile for a better clinical and neurobiological definition.

L-type calcium channels and psychiatric disorders: A brief review.

Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke. Calcium channel blockers have also been studied clinically in psychiatric conditions such as mood disorders and substance abuse/dependence, yielding conflicting results. In this review, we begin with a summary of LTCC pharmacology. For each category of disorder, this article then provides a review of animal and human data. In particular, we extensively focus on animal models of depression and clinical trials in mood disorders and substance abuse/dependence. Through examining rationale and study design of published clinical trials, we provide some of the possible reasons why we still do not have definitive evidence of efficacy of calcium-channel antagonists for mood disorders. Refinement of genetic results and target phenotypes, enrollment of adequate sample sizes in clinical trials and progress in physiologic and pharmacologic studies to synthesize tissue and isoform specific calcium channel antagonists, are all future challenges of research in this promising field. © 2010 Wiley-Liss, Inc.

Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder.

Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene.

Sensitivity to change and predictive validity of the MOODS-SR questionnaire, last-month version.

BACKGROUND: Instruments that are intended to measure change over time need to emphasize sensitivity to change as a central property. The aims of this report are to test whether the MOODS-SR, a measure of mood spectrum symptomatology, is sensitive to changes during acute and continuation treatment of depression and whether residual mood spectrum symptoms predict relapse in the subsequent 6 months. METHODS: The study sample includes 316 patients with nonpsychotic depression participating in the protocol 'Depression: the search for treatment-relevant phenotypes'. Patients were initially randomized to selective serotonin reuptake inhibitors or interpersonal psychotherapy and then treated for 9 months using an algorithm-based protocol. Measures of mood symptomatology included the self-report version of the structured clinical interview for mood spectrum (MOODS-SR), the Quick Inventory for Depressive Symptomatology and the Hamilton Rating Scale for Depression. RESULTS: Repeated-measures ANOVA indicates that during the acute phase MOODS scores decrease significantly from baseline to weeks 6 and 12. This decrease was significantly different (p < 0.001) between those who remitted and those who did not remit on the depressive, the rhythmicity component and the total score. Nonrelapsing subjects had stable scores across the continuation phase, while among relapsing subjects, a significant increase was found in the depressive component (p < 0.001), the rhythmicity component (p = 0.024) and the total score (p < 0.001), at 2 months, followed by a decrease from 2 to 6 months. Scores on the depressive component at the entry into continuation predicted relapse in the subsequent 6 months. CONCLUSIONS: Our findings suggest that the MOODS-SR is sensitive to change in depression status and may help the clinician to detect symptoms and signs not considered by established symptom severity scales.

A multidimensional spectrum approach to post-traumatic stress disorder: comparison between the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) and the Self-Report instrument (TALS-SR).

Dimensional approaches to psychiatric disorders have shown an increased relevance in the ongoing debate for the forthcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. In line with previously validated instruments for the assessment of different mood, anxiety, eating and psychotic spectra, we tested the validity and reliability of a newly developed Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS). The instrument is based on a multidimensional approach to post-traumatic stress spectrum that includes a range of threatening or frightening experiences, as well as a variety of potentially significant losses, to which an individual can be exposed. Furthermore, it explores the spectrum of the peritraumatic reactions and post-traumatic symptoms that may ensue from either type of life events, targeting soft signs and subthreshold conditions, as well as temperamental and personality traits that may constitute risk factors for the development of the disorder. The aim of the present study is to describe the reliability of the self-report version of the SCI-TALS: the TALS-SR. Thirty patients with PTSD and thirty healthy control subjects were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Half of the patients and controls received the TALS-SR first and the SCI-TALS after 15 days; for the other half of the sample, the order of administration was reversed. Agreement between the self-report and the interview formats was substantial. Intraclass correlation coefficients ranged from 0.934 to 0.994, always exceeding the threshold of 0.90. Our findings provide substantial support for the reliability of the TALS-SR questionnaire.

Efficacy of electroconvulsive therapy in Fahr disease associated with bipolar psychotic disorder: a case report.

We report a case of a patient with Fahr disease affected by bipolar disorder type I with psychotic symptoms. The complex clinical picture, characterized by both neurological and psychiatric symptoms, proved to be partially or completely resistant to several pharmacological trials. On the contrary, a marked improvement of clinical picture occurred after a cycle of 10 sessions of electroconvulsive therapy, followed by a complete and sustained resolution of mood, cognitive, motor, and behavioral symptoms during the next 4 years.

Treatment-emergent mania/hypomania in unipolar patients.

OBJECTIVE: The aim of this study was to estimate the incidence of treatment-emergent mania/hypomania (TEMH) and to describe the clinical characteristics of patients with major depression experiencing this event during treatment with a selective serotonin reuptake inhibitor (SSRI) and/or interpersonal psychotherapy (IPT). METHODS: Following an algorithm-based protocol, 344 patients with major depression confirmed with the Structured Clinical Interview for DSM-IV disorders were treated with an SSRI, interpersonal psychotherapy, or their combination for nine months. The emergence of mania/hypomania was carefully monitored throughout the study using the Young Mania Rating Scale and clinical assessment. RESULTS: Overall, eight patients experienced TEMH. The incidence of this event was 3.0% in patients treated with an SSRI and 0.9% in patients treated with IPT alone. Among patients treated with an SSRI, the difference between sites was higher than expected by chance alone (6.8% at Pisa and 0% at Pittsburgh, p = 0.002). Despite the adoption of an identical protocol at the two sites, some demographic and clinical characteristics of participants may account for this unexpected result. Alternatively, the greater number of episodes and earlier age of onset at the Pittsburgh site suggests that the unipolar course of illness was more clearly established prior to study entry. CONCLUSIONS: TEMH is an infrequent event, occurring in 2.3% of patients treated for major depression. Nevertheless, its consequences are clinically relevant and require prompt and appropriate therapeutic interventions. For this reason, recognising those patients at risk for such an event is of paramount clinical significance. The observed difference in the incidence of TEMH between the two sites requires further investigation.

Platelet 18 kDa Translocator Protein density is reduced in depressed patients with adult separation anxiety.

RATIONALE: Recent studies indicate that Adult Separation Anxiety Disorder (ASAD) may represent a discrete diagnostic entity worthy of attention. Adults with separation anxiety report extreme anxiety and fear about separations from major attachment figures (partner, children or parents). These symptoms affect individual's behavior, lead to severe impairment in social relationships and are not better accounted for by the presence of agoraphobia. In a previous study we found platelet expression reduction of the 18 kDa Translocator Protein (TSPO) (the new nomenclature for the peripheral-type benzodiazepine receptor) in patients with panic disorder who also fulfilled the diagnostic criteria for ASAD. OBJECTIVES: To explore whether separation anxiety might be a factor differentiating TSPO expression in a sample of patients with major depression. METHODS: The equilibrium binding parameters of the specific TSPO ligand [3H]PK 11195 were estimated on platelet membranes from 40 adult outpatients with DSM-IV diagnosis of MDD, with or without separation anxiety symptoms, and 20 healthy controls. Patients were assessed by SCID-I, HAM-D, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-report Checklist (ASA-27). RESULTS: A significant reduction of platelet TSPO density mean value was found in depressed patients with associated ASAD symptoms, while no significant differences were found between depressed patients without ASAD and the control group. Individual TSPO density values were significantly and negatively correlated with both SCI-SAS-A and ASA-27 total scores, but not with HAM-D total score or HAM-D anxiety/somatization factor score. CONCLUSIONS: The reduction of platelet TSPO density in our sample of patients with depression was specifically related to the presence of ASAD. These data suggest that TSPO expression evaluation is a useful biological marker of ASAD.

Borderline personality disorder and mood spectrum.

Several lines of evidence have raised the question of whether Borderline Personality Disorder (BPD) is an independent disease entity or it might be better conceptualized as belonging to the spectrum of mood disorders. This study explores a wide array of lifetime mood features (mood, cognitions, energy, and rhythmicity and vegetative functions) in patients with BP and mood disorders. The sample consisted of 25 BPD patients who did not meet the criteria for bipolar disorders, 16 bipolar disorders patients who did not meet the criteria for BPD, 19 unipolar patients who did not meet the criteria for BPD, and 30 non-clinical subjects. Clinical diagnoses were determined by administering the structured clinical interviews for DSM-IV disorders. The Mood Spectrum Self-Report (MOODS-SR) was used for measuring lifetime mood phenomenology. Clinical subjects displayed higher mean scores than normal subjects in all domains of the MOODS-SR, and BPD patients displayed higher scores than unipolar patients in the Mood and Cognition depressive subdomains. Differences between patients with BP and bipolar disorders on MOODS psychopathology did not attain statistical significance for any (sub)domain considered. The results of this study are consistent with previous findings suggesting the importance of mood dysregulations in patients with BPD.

Different temperament and character dimensions correlate with panic disorder comorbidity in bipolar disorder and unipolar depression.

BACKGROUND: This study aimed to investigate temperament and character correlates of panic disorder (PD) comorbidity in euthymic patients with bipolar disorder (BD) or unipolar depression (UD). METHODS: Temperament and character were assessed using the Temperament and Character Inventory Revised (TCI-R) in 181 patients (70 patients with BD-I, 51 patients with BD-II and 60 with UD) in a euthymic state for at least 2 months. RESULTS: PD was diagnosed in 14.3% of BD-I patients, 31.4% of BD-II and 40% of UD. BD patients with PD, when compared with BD patients without PD, had higher scores on harm avoidance (OR=1.04; 95% CI=1.02-1.07; p=0.002). Patients with UD and PD, when compared to patients with UD without PD, had higher scores on social acceptance (OR=1.27; 95% CI=1.08-1.49; p=0.004). CONCLUSION: Different temperament and character dimensions correlated with PD comorbidity in BD and UD patients, suggesting different underlying pathophysiological mechanisms.

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS).

BACKGROUND: DSM-IV identifies three stress response disorders (acute stress (ASD), post-traumatic stress (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. METHODS: This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Study participants, enrolled at 6 Italian Departments of Psychiatry, included consecutive patients with PTSD (N = 48), CG (N = 44), and controls (N = 48). RESULTS: We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. CONCLUSION: These results support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations.

The neurobiology and clinical significance of depersonalization in mood and anxiety disorders: a critical reappraisal.

Depersonalization and derealization occur on a continuum of situations, from healthy individuals to a severely debilitating disorder where the symptoms can persist chronically. Since 1960s, different neurobiological models have been hypothesized and they have been associated with the temporal lobes. Recent advances in the functioning of the limbic system and the application of Geschwind's concept of disconnection in the cortico-limbic networks, pointed the role of the amygdala and its connections with medial prefrontal cortex and anterior cingulate cortex, the same structures that are strictly interlinked with the neurobiology of emotions and affective disorders. In this paper, we hypothesize that depersonalization may represent a clinical index of disease severity, poorer response to treatment and high level of comorbidity, in mood and anxiety disorders, discussing the neurobiology of depersonalization and the available clinical evidence.

Reasons for substance use and vulnerability factors in patients with substance use disorder and anxiety or mood disorders.

This cross-sectional study examined the reasons for substance use and the presence of vulnerability factors such as substance sensitivity, sensation seeking, and symptoms related to the attention deficit hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) and comorbid mood and anxiety disorders by using the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a novel instrument designed to explore the spectrum of substance use and its clinical correlates. Study participants included 61 patients with SUD and mood or anxiety disorder, and two comparison groups including 35 patients with SUD only and 50 controls not in treatment for mental disorders or SUD. We found that patients with co-morbid mood or anxiety disorder had significantly higher scores on the SCI-SUBS domains 'substance sensitivity' and 'self-medication' as compared to those with SUD only. Scores on 'sensation seeking' and 'ADHD' domains were similar between both groups of patients and higher than in controls. Patients with comorbid mood or anxiety disorders showed a higher sensitivity to substances and were more prone to self-medication than those with SUD only. These characteristics should be taken into account in the diagnostic assessment and in long-term treatment to decrease the risk of relapse.

Social anxiety and obsessive-compulsive spectra: validation of the SHY-SR and the OBS-SR among the Spanish population.

The study focuses on the adaptation into Spanish and on the validation of the Social Phobia Spectrum Self-Report (SHY-SR) and the Obsessive-Compulsive Spectrum Self-Report (OBS-SR). The questionnaires were designed to measure a broad range of subtle and atypical features related to social anxiety and obsessive-compulsive phenomenology, respectively. Sixty-two outpatients who met DSM-IV criteria for social phobia (SP, n = 20), obsessive-compulsive disorder (OCD, n = 22) and major depression (MD, n = 20), and 25 non-clinical subjects participated. The spectra questionnaires were administered along with the Liebowitz Social Anxiety Scale and the Maudsley Obsessional Compulsive Inventory. The instruments proved to have satisfactory internal consistency and test-retest reliability. Convergent validity with other instruments was excellent for the SHY-SR and moderate for the OBS-SR. Both questionnaires were able to detect differences between patients with the disorder of interest (SP in the case of the SHY-SR scores and OCD in the case of the OBS-SR scores) and either normal controls or patients with MD. Receiver-Operating Characteristic Curve analyses were conducted to determine cut-off values in the Spanish versions of the questionnaires denoting the presence of significant SP and OCD symptomatology. Are the questionnaires available on the website?

Multidimensional assessment of the Panic-Agoraphobic Spectrum: reliability and validity of the Spanish version of the PAS-SR.

The present study reports on the psychometric properties of the adaptation into Spanish of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR). Drawing on a dimensional and longitudinal perspective of psychopathology, the PAS-SR was designed to measure a wide array of lifetime Panic-Agoraphobic features. Participants included outpatients with a DSM-IV-TR diagnosis of panic disorder (n=26) or major depression (n=28), and a normal control group (n=41). Internal consistency and test-retest reliability were excellent for the total score, and moderate to excellent for most domains. Significant and high correlations between PAS-SR scores and instruments measuring similar constructs indicated good concurrent validity. The findings support the discriminant validity of the questionnaire. Patients with a diagnosis of panic disorder attained higher scores than normal controls on all domains, and displayed higher scores than patients with major depression on five of the eight domains.

Social anxiety disorder comorbidity in patients with bipolar disorder: a clinical replication.

BACKGROUND: The authors investigated frequency, clinical correlates and onset temporal relationship of social anxiety disorder (SAD) in adult patients with a diagnosis of bipolar I disorder. METHODS: Subjects were 189 patients whose diagnoses were assessed by the Structured Clinical Interview for DSM-III-R-Patient Version. RESULTS: Twenty-four patients (12.7%) met DSM-III-R criteria for lifetime SAD; of these, 19 (10.1% of entire sample) had SAD within the last month. Significantly more bipolar patients with comorbid SAD also had substance use disorders compared to those without. On the HSCL-90, levels of interpersonal sensitivity, obsessiveness, phobic anxiety and paranoid ideation were significantly higher in bipolar patients with SAD than in those without. Bipolar patients with comorbid SAD recalled separation anxiety problems (school refusal) more frequently during childhood than those without. Lifetime SAD comorbidity was associated with an earlier age at onset of syndromal bipolar disorder. Pre-existing OCD tended to delay the onset of bipolarity. CONCLUSIONS: Social anxiety disorder comorbidity is not rare among patients with bipolar disorder and is likely to affect age of onset and phenomenology of bipolar disorder. These findings may influence treatment planning and the possibility of discovering a pathophysiological relationship between SAD and bipolarity.