Bipolar-panic disorder comorbidity within bipolar disorder families: a study of siblings

Objectives:  Although anxiety disorders often co-occur with bipolar disorder in clinical settings, relatively few studies of bipolar disorder have looked specifically at panic comorbidity. This report examines lifetime panic comorbidity within a sample of families with a history of bipolar disorder.
Methods:  One hundred and nine probands with bipolar disorder and their 226 siblings were interviewed as part of a family-genetic study. Logistic regression was used to model bipolar disorder as a predictor of comorbid panic in those with affective disorder, with age at interview and gender included as covariates.
Results:  The percentage with panic attacks was low in those without affective disorder (3%) compared with those with unipolar depression (22%) or bipolar disorder (32%). Panic disorder was found only in those with affective disorder (6% for unipolar, 16% for bipolar). When bipolar disorder and unipolar disorder were compared, controlling for age and sex, having bipolar disorder was associated with panic disorder (OR = 3.0, 95% CI = 1.1, 7.8) and any panic symptoms (OR = 2.0, CI = 1.0,3.8) and more weakly with the combination of panic disorder and recurrent attacks (OR = 1.8, CI = 0.9, 3.5).
Conclusions:  The absence of panic disorder and the low prevalence of any panic symptoms in those without bipolar or unipolar disorder suggest that panic is associated primarily with affective disorder within families with a history of bipolar disorder. Furthermore, panic disorder and symptoms are more common in bipolar disorder than in unipolar disorder in these families.     

Polarity at illness onset in bipolar I disorder and clinical course of illness

Objectives:  Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder.
Methods:  We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210).
Results:  Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features.
Conclusions:  Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder.     

Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine

Objective:  We conducted a study of clinical presentation and family history in patients responsive to either of two commonly used mood stabilizers, lithium and lamotrigine.
Methods:  The sample included 164 subjects from 21 families of bipolar probands, 14 responders to lithium and seven to lamotrigine. Diagnostic information on first-degree relatives was obtained in a blind fashion through a combination of direct interviews (SADS-L) and family history assessments (FH-RDC).
Results:  The probands differed with respect to clinical course (episodic in the lithium group, rapid cycling in the lamotrigine group), and comorbidity (panic attacks and substance abuse in the lamotrigine group). The relatives of lithium responders had significantly higher risk of bipolar disorder while relatives of lamotrigine responders had higher prevalence of schizoaffective disorder, major depression and panic attacks.
Conclusions:  These findings suggest that lithium- and lamotrigine-responsive patients differ with respect to course of illness, comorbidity and family history and may represent distinct subtypes of bipolar disorder.     

Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study

Objective:  Symptoms of bipolar disorder are increasingly recognized among children and adolescents, but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms.
Methods:  We examined prospective outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II outpatients participating in a multicenter clinical effectiveness study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Age at illness onset was identified retrospectively by clinician assessment at study entry.
Results:  Compared to patients with onset of mood symptoms after age 18 years (n = 1,187), those with onset before age 13 years (n = 1,068) experienced earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over the two-year follow-up. Outcomes for those with onset between age 13 and 18 years (n = 1,403) were generally intermediate between these two groups.
Conclusion:  Consistent with previous reports in smaller cohorts, adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence, chronicity of mood symptoms, and functional impairment during prospective observation.     

Ten-year diagnostic consistency of bipolar disorder in a first-admission sample

Ruggero CJ, Carlson GA, Kotov R, Bromet EJ. Ten-year diagnostic consistency of bipolar disorder in a first-admission sample.
Bipolar Disord 2010: 12: 21–31. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.
Objectives:  A number of reports have examined the stability of the diagnosis of schizophrenia, but fewer studies have considered the long-term consistency of a bipolar diagnosis or factors that influence the likelihood of a diagnostic change. The present study sought to estimate how consistently a bipolar diagnosis was made across a 10-year period and factors associated with consistency, particularly demographic and clinical characteristics, childhood-related factors, and illness course.
Methods:  The sample included 195 first-admission patients presenting with psychosis who were assessed soon after hospitalization and at 6-month, 2-year, and 10-year follow-up and diagnosed with bipolar disorder on at least one of these assessments. Diagnoses were made using best-estimate procedures and were blind to all previous consensus diagnoses. Respondents who were consistently diagnosed with bipolar disorder were compared to those whose diagnosis shifted across assessments.
Results:  Overall, 50.3% (n = 98) of the 195 respondents were diagnosed with bipolar disorder at every available assessment, but 49.7% (n = 97) had a diagnostic shift to a non-bipolar disorder at least once over the course of the 10-year study. Childhood psychopathology and poorer illness course were among the few variables associated with increased odds of a change in diagnosis.
Conclusions:  Even with optimal assessment practices, misdiagnosis of bipolar disorder is common, with complex clinical presentations often making it difficult to consistently diagnose the disorder over the long term.     

Ultra-brief pulse ECT in bipolar and unipolar depressive disorder: differences in speed of response

Objectives:  There is little evidence for differences in response and speed of response to electroconvulsive therapy (ECT) between patients with bipolar and patients with unipolar depressive disorder. In the only prospective study to date, Daly et al. (Bipolar Disord 2001; 3: 95–104) found patients with bipolar depression to show more rapid clinical improvement and require fewer treatments than unipolar patients. In this study, response and speed of response of patients with unipolar and bipolar depression treated with ultra-brief pulse ECT were compared.
Methods:  All patients (n = 64) participated in a randomized trial comparing ultra-brief pulse bifrontal ECT at 1.5 times seizure threshold and unilateral ECT at 6 times seizure threshold. Thirteen patients (20.3%) had DSM-IV-defined bipolar depression. The Hamilton Rating Scale for Depression and Clinical Global Impression scale were administered at baseline and repeated weekly during and after the course of treatment by a blinded rater. At the same time point, the Beck Depression Inventory and the Patient Global Impression scale were administered. Speed of response was analyzed using survival analyses.
Results:  Patients with bipolar and unipolar depression did not differ in rates of response or remission following the ECT course, nor in response to unilateral or bifrontal ECT. Patients with bipolar depression, however, showed a more rapid response than patients with unipolar depression.
Conclusions:  Patients with bipolar depression tend to show more rapid clinical improvement with ECT than patients with unipolar depression.     

No evidence of attentional deficits in stabilized bipolar youth relative to unipolar and control comparators

Objective: The purpose of this study was to determine the presence or absence of attentional problems and prior diagnosis of ADHD in a cohort of stabilized bipolar I relative to unipolar and normal control.
Method: Indices of attention were obtained from bipolar (n = 44), unipolar (n = 30), and normal controls (n = 45). Measures included: Freedom from Distractibility (FD) Composite Index of the WISC III, Conners' Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), and a checklist measure of subjective cognitive/attentional problems (SIP-AV).
Results: Bipolar (6.8%), unipolar (10%), and no control youth report a prior diagnosis of ADHD. No significant group or sex differences were observed on FD Composite Index, various CPT indices, or the WCST. Despite normative attentional function by objective testing, subjectively experienced cognitive problems in the clinical probands were reported.
Conclusions: This cohort of well-functioning bipolar youth diagnosed on average 3–4 years prior to assessment do not possess attentional deficits based on a variety of objective tests compared to unipolar or control youth, but self report subjective difficulties in attentional/problem solving ability. In contrast to other authors, we do not find that bipolar youth have high rates of comorbid ADHD.     

Rapid switching of mood in families with familial bipolar disorder

Objective:  Rapid switching of moods in bipolar disorder has been associated with early age at onset, panic comorbidity, and suicidality. This study aims to confirm these associations and investigate other potential correlates of rapid switching of mood using families from a multisite bipolar linkage study.
Methods:  The subjects were comprised of 1,143 probands and relatives with diagnosis of bipolar disorder. All subjects were interviewed directly with a standard diagnostic instrument, and all subjects who met criteria for bipolar disorder were asked if their moods had ever switched rapidly.
Results:  Individuals with rapid mood switching had significantly earlier age at onset (18 versus 21 years, p < 0.00001), higher comorbid anxiety (47% versus 26%, p < 0.00001) and substance use disorders (52% versus 42%, p = 0.0006), higher rate of violent behavior (6% versus 3%, p < 0.004), suicidal behavior (46% versus 31%, p < 0.00001), and nonsuicidal self-harm (13% versus 6%, p < 0.0002). Multiple logistic regression analysis found significant net effects on rapid mood switching for early emergence of symptoms [odds ratio (OR) = 0.62; 95% confidence interval (CI): 0.45–0.85]; anxiety comorbidity (OR = 2.31; 95% CI: 1.34–3.98); and hypersensitivity to antidepressants (OR = 2.05; 95% CI: 1.49–2.83) as the strongest predictors.
Conclusions:  This confirms earlier reports associating rapid switching with a more complex clinical course, in particular early emergence of bipolar symptomatology, antidepressant activation, and anxiety comorbidity. These results support a clinical differentiation of bipolar disorder into subtypes based on symptom stability.     

Short-term course of neuropsychological abilities in middle-aged and older adults with bipolar disorder

Objectives:  There are few longitudinal studies of neurocognition in bipolar disorder, and the short-term course of cognitive deficits in later-life bipolar disorder is unknown.
Methods:  We administered a battery of neurocognitive tests, repeated 1–3 years after baseline, to 35 community-dwelling outpatients with bipolar disorder (mean age = 58), and compared their performance on a composite measure of cognitive functioning to that of demographically matched samples of normal comparison subjects (NCs; n = 35) and patients with schizophrenia (n = 35). Using regression analyses, we examined group differences in baseline performance, trajectory of change over time, and variability in performance across time. Within the bipolar group, we examined the impact of baseline severity and change in severity of psychiatric symptoms on intra-individual change in neurocognitive performance.
Results:  At baseline, the group with bipolar disorder differed in overall neurocognitive functioning from the NCs, but did not differ significantly from the schizophrenia group. The bipolar group did not differ from the NCs or schizophrenia group in the mean trajectory of change between time-points, but the bipolar patients showed more intra-individual variability over time than the NCs or schizophrenia group. In the bipolar group, change in neurocognitive function was not related to baseline or change in psychiatric symptom severity.
Conclusions:  Middle-aged and older community-dwelling adults with bipolar disorder have greater short-term variability in level of neurocognitive functioning relative to NCs or people with schizophrenia. The developmental course of and risk factors for cognitive deficits in bipolar disorder should be examined in future longitudinal studies.     

Oxcarbazepine add-on in the treatment of refractory bipolar disorder

Objective:  To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions.
Methods:  We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales.
Results:  OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 ± 556.11 mg/day and the mean duration of follow-up was 31.60 ± 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects.
Conclusion:  OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.     

Comorbidity of adult attention-deficit hyperactivity disorder and bipolar disorder: prevalence and clinical correlates

The aim of this study was to determine the frequency of adult attention deficit hyperactivity disorder (ADHD) comorbidity with lifetime bipolar disorder, and the influence of this comorbidity on various demographic and clinical variables in patients. Patients (n = 159) with a previous diagnosis of bipolar disorder (79 female, 80 male) were included in this study. All patients were interviewed for the presence of current adult and childhood ADHD diagnosis and other axis I psychiatric disorder comorbidities using the structured clinical interview for DSM-IV (SCID) and the Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime Version (K-SADS-PL). The subjects also completed a Wender Utah rating scale (WURS-25) and a Current Symptoms Scale for ADHD symptoms. In particular, patients’ clinical characteristics, the age of onset of bipolar disorder, and the number of episodes were noted. Twenty-six of the 159 bipolar patients (16.3%) were diagnosed with adult ADHD, while another subgroup of patients (n = 17, 10.7%) received a diagnosis of childhood ADHD but did not fulfill criteria for adult ADHD. Both of these two subgroups (patients with adult ADHD, and patients with only childhood ADHD) had an earlier age of onset of the disease and a higher number of previous total affective or depressive episodes than those without any lifetime ADHD comorbidity. However only bipolar patients with adult ADHD comorbidity had higher lifetime comorbidity rates for axis I psychiatric disorders, such as panic disorder and alcohol abuse/dependence, compared to patients without lifetime ADHD. Bipolar patients with comorbid adult ADHD did not differ from bipolar patients with comorbid childhood ADHD in terms of any demographic or clinical variables except for adult ADHD scale scores. In conclusion, ADHD is a common comorbidity in bipolar patients, and it adversely affects the course of the disease and disrupts the social adjustment of the patients. Regular monitoring of ADHD will help to prevent problems and complications that could arise in the course of the disease, particularly in patients with early onset bipolar disorder.     

Smaller amygdala is associated with anxiety in patients with panic disorder

Aims:  Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety.
Methods:  Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State–Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety.
Results:  Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = −2.248, d.f. = 55, P  = 0.029; right: t = −2.892, d.f. = 55, P  = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,−6,−16], Z score = 3.92, family-wise error-corrected P  = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = −0.545, P  = 0.016).
Conclusions:  These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential

Objectives:  Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups.
Methods:  P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM-IV criteria and the Structured Clinical Interview for DSM-IV; and from 56 healthy controls.
Results:  The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups ( F _3,204 = 5.47, p = 0.001, and post-hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group ( F _3,204 = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups.
Conclusions:  The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.     

Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective

Objectives:  Distinguishing clinical characteristics of bipolar patients who have made a suicide attempt may help to identify at-risk individuals. We sought to identify such factors and to consider them within a stress-diathesis model of suicidal behavior.
Methods:  Patients with bipolar disorder (N = 96) were compared with respect to the presence or absence at baseline evaluation of a history of suicide attempt. We used multiple logistic regression analysis to assess the unique associations of independent variables to history of a past suicide attempt.
Results:  The regression analysis showed that a history of suicide attempt in bipolar disorder was associated with greater recent suicidal ideation, more psychiatric hospitalizations, lifetime aggressive traits and an earlier age at onset of a first mood episode.
Conclusions:  Aggressive traits and early treatment of mood disorders, especially major depressive episodes, are potential targets for suicide prevention in bipolar disorder.     

The longitudinal course of cognition in older adults with bipolar disorder

Objectives:  Epidemiological studies suggest that elders with bipolar disorder (BD) may be at increased risk for dementia compared to the general population. We sought to investigate whether older adults with BD would present with more cognitive dysfunction than expected for their age and education, and whether they would experience a more rapid cognitive decline over three-year prospective follow-up.
Methods:  Thirty-three subjects age ≥ 50, mean (SD) age 69.7 (7.9) years, with BD I (n = 28) and II (n = 5) had neuropsychological examination at baseline and longitudinally over three years. All subjects were administered the Dementia Rating Scale (DRS) when euthymic. Thirty-six mentally healthy comparators ('controls'), equated on age and education, were selected from ongoing studies in our research center examining the longitudinal relationship between late-life mood disorders and cognitive function.
Results:  Compared to mentally healthy comparators, subjects with BD performed significantly worse on the DRS at baseline [mean (SD) 135.2 (4.7); n = 33 versus 139.5 (3.3); n = 36], and over follow-up [131.9 (7.7); n = 14 versus 139.1 (3.4); n = 22]. There was a group-by-time interaction between the subjects with BD and the controls [group × time: F (1,64) = 5.07, p = 0.028].
Conclusions:  In our study, older adults with BD had more cognitive dysfunction and more rapid cognitive decline than expected given their age and education. Cognitive dysfunction and accelerated cognitive decline may lead to decreased independence, with increased reliance on family and community supports, and potential placement in assisted-living facilities.     

Can body mass index help predict outcome in patients with bipolar disorder?

Objective:  Several studies have reported higher prevalence of obesity in patients suffering from bipolar disorder (BD). To study the relation of elevated body mass index (BMI) in patients with BD more closely, we investigated differences in sociodemographic, clinical, and medical characteristics with respect to BMI, with the hypothesis that BMI is related to prognosis and outcome.
Methods:  We measured the BMI of 276 subjects of a tertiary care sample from the Maritime Bipolar Registry. Subjects were 16 to 83 years old, with psychiatric diagnoses of bipolar I disorder (n = 186), bipolar II disorder (n = 85), and BD not otherwise specified (n = 5). The registry included basic demographic data and details of the clinical presentation. We first examined the variables showing a significant association with BMI; subsequently, we modeled the relationship between BMI and psychiatric outcome using structural equation analysis.
Results:  The prevalence of obesity in our sample was 39.1%. We found higher BMI in subjects with a chronic course (p < 0.001) and longer duration of illness (p = 0.02), lower scores on the Global Assessment of Functioning Scale (p = 0.02), and on disability (p = 0.002). Overweight patients had more frequent comorbid subthreshold social (p = 0.02) and generalized anxiety disorders (p = 0.05), diabetes mellitus type II (p < 0.001), and hypertension (p = 0.001). Subjects who achieved complete remission of symptoms on lithium showed significantly lower BMI (p = 0.01).
Conclusions:  Our findings suggest that BMI is associated with the prognosis and outcome of BD. Whether this association is causal remains to be determined.     

Episodic course in obsessive-compulsive disorder

The course of obsessive–compulsive disorder (OCD) is variable, ranging from episodic to chronic. We hypothesised that the former course is more likely to be related to bipolar mood disorders. With the use of a specially constructed OCD questionnaire, we studied 135 patients fulfilling DSM-III-R criteria for OCD with an illness duration of at least 10 years and divided by course: 27.4% were episodic and 72.6% chronic. We compared clinical and familial characteristics and comorbidity. Univariate analyses showed that episodic OCD had a significantly lower rate of checking rituals and a significantly higher rate of a positive family history for mood disorder. Multivariate stepwise discriminant analysis revealed a positive and significant relationship between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar-II disorders, late age at onset and negative correlation with generalized anxiety disorder. These data suggest that the episodic course of OCD has important clinical correlates which are related to cyclic mood disorders. This correlation has implications for treatment and research strategies on the aetiology within a subpopulation of OCD. Received: 30 October 1997 / Accepted: 13 July 1998     

Traumatic life events in bipolar disorder: impact on BDNF levels and psychopathology

Background:  There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events. While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder, little is known about the neurobiological basis underlying this association. The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events (TE) have lower brain-derived neurotrophic factor (BDNF) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE.
Methods:  One-hundred and sixty-three consecutively recruited bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV (SCID) and standard protocol in order to evaluation psychopathology and clinical features. The reported TE was assessed using DSM-IV stem criteria for trauma (as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder). Subjects were divided into 2 groups according to presence or absence of lifetime TE. The levels of BDNF, comorbidity and other clinical features were compared between groups.
Results:  After adjusting for confounders, results indicated that bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001), anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those without a history of TE. There was no difference between the 2 groups in age of onset, presence of psychosis, other substance abuse and dependence, rapid cycling or suicide attempts.
Conclusions:  Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients. It is possible that a decrease in BDNF levels may account for increased comorbidity, but further prospective studies are required to confirm this.     

Four Clinical Types of Panic Disorders

Abstract: The authors attempted to classify panic disorders into four types according to a clinical course and accompanying neurotic or depressive symptoms. The characteristics of each type are as follows; type I: a single panic attack is the only symptom, type 11 : only panic attacks occur frequently without any accompanying neurotic or depressive symptoms, type III: a recurrence of panic attacks and the gradual development of neurotic symptoms, such as anticipatory anxiety, generalized anxiety, agoraphobia, or hypo-chondriasis, type IV: depressive symptoms develop in the course of recurring panic attacks. Type IV is further divided into three subtypes. Type IV- 1 : depressive symptoms develop secondary to panic attacks and major depression later coexists with panic disorder. Type IV- 2 : panic disorder continuously changed into major depression. Type IV- 3 : panic attacks and depressive symptoms are seen independently. The most common types are type III and type IV-1, and seem to be a core group of the panic disorder. Typical cases of each type are presented and underlying psychopathology is discussed.