Differences in course of illness between patients with bipolar II disorder with and without epileptiform discharges or other sharp activity on electroencephalograms: a cross-sectional study.

BACKGROUND: A diagnosis of bipolar II disorder requires that the symptoms cannot be better explained by a medical condition. Epilepsy is in some cases associated with an affective syndrome mimicking an unstable bipolar II disorder. Epileptiform discharges on electroencephalograms (EEGs) are typical, but not pathognomonic, for epilepsy. A previous study has found a high frequency of epileptiform discharges and other sharp activity among patients with bipolar disorder. The aim of the study was to identify if epileptic discharges or other sharp activity per se are associated with an altered course of illness among patients with bipolar II disorder. METHODS: Eighty six patients diagnosed with bipolar II disorder at two psychiatric departments were interviewed about prior course of illness and assessed with EEGs. The patients were split into two groups based on the presence (n = 12) or absence (n = 74) of epileptiform discharges or other sharp activity. Wilcoxon rank sum test, Fisher's exact test, and Pearson's chi squared test were used to assess differences between the groups on six variables of course of illness. RESULTS: Patients with epileptiform discharges or other sharp activity had a history of more hypomanic episodes per year (median (interquartile range (IQR)) 1.5 (3.2) vs. 0.61 (1.1), p = 0.0090) and a higher hypomania:depression ratio (median (IQR) 3.2 (16) vs. 1.0 (1.0), p = 0.00091) as compared to patients without. None of the patients with epileptiform discharges or other sharp activity had self-reported epileptic seizures in their history. CONCLUSIONS: Epileptiform discharges or other sharp activity on EEGs are associated with more hypomanic episodes and an increased hypomania:depression ratio. Our results warrant replication in prospective studies, but suggest that EEG findings could be of prognostic importance for patients diagnosed with bipolar II disorder in psychiatric care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00201526 ).

Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries.

BACKGROUND: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. METHODS: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. RESULTS: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. CONCLUSIONS: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Borderline patients have difficulties describing feelings; bipolar II patients describe difficult feelings. An alexithymia study.

OBJECTIVE: Apparent similarities between borderline personality disorder (BPD) and bipolar II disorder (BIP-II) contribute to clinical difficulties in distinguishing between the disorders. Here, we aimed to explore how subjective Difficulties with the Identification and Description of Feelings (DIDF), a major constituent of the alexithymia construct and assessed as a part of the Toronto Alexithymia Scale (TAS), are related to relationship problems and health complaints in these groups. METHODS: Twenty-two patients with BPD; 22 patients with BIP-II; and 23 healthy controls (HC) completed TAS. Health complaints, including symptoms associated with mood swings, were assessed with the Giessener Subjective Complaints List (Giessener Beschwerdebogen-GBB), and relationship problems with the Health of the Nation Outcome scale, Relationship item (HoNOSR). Bivariate correlations were run. RESULTS: Both patient groups had high DIDF and GBB scores. In BPD only, there was a significant positive correlation between DIDF and HoNOSR. In BIP-II only, there was a significant positive correlation between DIDF and GBB total score. In BIP-II, DIDF correlated highly with those GBB subscales assessing symptoms typically occurring during bipolar mood swings (cardiovascular and gastrointestinal symptoms, exhaustion). CONCLUSION: Our results suggest that in BPD, high DIDF scores represent genuine problems with identifying and describing emotions which are expected to correlate with relationship problems. In BIP-II, high DIDF scores could potentially represent difficulties with understanding the unpredictable symptoms of bipolar mood swings. The findings suggest that difficulties with identifying and describing feelings in patients should be carefully explored to increase the validity of the diagnostic evaluation.

Patterns of altered regional brain glucose metabolism in borderline personality disorder and bipolar II disorder.

OBJECTIVE: The relationship between borderline personality disorder (BPD) and bipolar II disorder (BIP-II) is disputed but understudied. Here, we investigated brain glucose metabolism in these patient groups and healthy control subjects (HCs). METHODS: Sixty-five subjects, 22 BPD (19 females), 22 BIP-II (17 females), and 21 HC (14 females), were examined using 2-deoxy-2[18F]-fluoro-d-glucose positron-emission tomography (PET) scanning. Only patients without reciprocal comorbidity were recruited; BPD participants without bipolar spectrum pathology; BIP-II participants without cluster A/B personality pathology. Groups were compared pairwise. Associations with mood state and childhood trauma were analyzed. RESULTS: Both patient groups exhibited hypometabolism compared with HCs in insula, brainstem, and frontal white matter. Additionally, BPD patients showed hypometabolism in hypothalamus, midbrain, and striatum; BIP-II patients in cerebellum. Uncorrected analyses showed cortical areas of higher metabolism in BIP-II than BPD, and associations with clinical variables differed between the groups. CONCLUSION: Reduced metabolism in the insula regions was shown in both disorders, suggesting shared pathophysiological mechanisms. The observed patterns of altered metabolism specific to each patient group, as well as the uncorrected results, may also suggest differential pathophysiology. However, these latter findings must be interpreted cautiously given the non-significant corrected results in the direct comparison between the disorders.

Recovery from major depressive disorder episode after non-pharmacological treatment is associated with normalized cytokine levels.

BACKGROUND: Several lines of evidence show that the immune system is implicated in the pathophysiology of major depressive disorder (MDD) and that treatment with antidepressants affects cytokine and C-reactive protein (CRP) levels. Few studies have investigated immune markers during non-pharmacological treatment. In this follow-up study, we investigated whether CRP and elevated plasma cytokine levels observed before treatment of an acute episode of MDD are normalized during non-pharmacological treatment. METHODS: We obtained clinical assessments and blood for CRP and cytokine analysis from 50 unmedicated MDD patients, and cytokine levels from healthy controls. The patients received 'therapy as usual' for 12 weeks, and the assessments were then repeated. Of the 43 completers, 29 patients did not receive medication. RESULTS: In the patients receiving treatment without antidepressants, the depressive symptoms and the plasma levels of eight cytokines (interleukin (IL)-1Ra, IL-5,-6,-8,-10, G-CSF, IFN-γ, and TNF-α) were significantly reduced (P = 0.002-0.048). The cytokine levels were no longer different from the controls. The plasma CRP level did not change. CONCLUSION: Cytokine plasma levels normalized during recovery from an acute depressive episode in MDD without antidepressant treatment. These findings may have implications for the understanding of the role of the immune system in depression and recovery from depression.

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Somatic and cognitive symptoms as indicators of potential endophenotypes in bipolar spectrum disorders: an exploratory and proof-of-concept study comparing bipolar II disorder with recurrent brief depression and healthy controls.

BACKGROUND: We examined whether somatic symptoms reported by patients with bipolar spectrum disorder (BSD), in this study defined as bipolar II (BD-2) or recurrent brief depression with (RBD-H) or without (RBD-O) a history of hypomanic symptoms might point to the possible underlying disease markers (endophenotypes). We hypothesized that somatic symptoms that are possible indirect indicators of endophenotypes should be more prevalent among patients than among healthy controls; should not correlate with neuroticism; should not correlate with the severity of current mental status (e.g., anxiety, depression); and should not correlate with the use of psychotropic drugs including antiepileptics or be explained by co-morbid medical diseases. METHODS: Sixty-one patients (BD-2: n=21; RBD-H: n=19; RBD-O: n=21) were compared with 21 healthy controls. Assessments included a 123-item somatic symptom checklist; assessments for neuroticism, anxiety and depression. Candidate somatic symptoms were selected using a 4-step inclusion/exclusion procedure. RESULTS: Seven symptoms survived in all three groups: general (fatigue, feeling exhausted); sensory (leaden sensation in legs, pain in the body, impaired sense of smell); cognitive (loss of memory) and autonomic (excessive perspiration). In addition 15 symptoms survived in one or two groups (examples: impaired hearing, hypersensitivity to sound, inability to find words). LIMITATIONS: Possible selection bias and small sample size precludes firm conclusions with regards to specific symptoms. CONCLUSION: Our approach identified symptoms for which an association with BSDs has been suggested previously, as well as symptoms not commonly associated with BSDs. The findings support the feasibility and validity of using assessment of somatic symptoms as an approach to identify potential endophenotypes in BSDs.

Risk factors of cycle acceleration in acutely admitted patients with bipolar disorder.

OBJECTIVE: To identify risk factors associated with cycle acceleration (CA), that is, progressive decrease in duration of syndrome-free intervals between affective episodes, in acutely admitted patients with bipolar disorder (BD). METHOD: All patients (n = 210) with BD I (67%) and BD II (33%) (DSM-IV) acutely admitted to a hospital serving a catchment area were compared in retrospect with regard to a positive or negative history of CA. Putative risk factors of CA with a P-value <0.05 in uni-variate tests were secondly entered into a logistic regression model. RESULTS: The logistic regression model was statistically significant (P < 0.0001) and explained between 45.3% and 60.5% of the variance of CA status. 83.7% of the cases were correctly classified with a sensitivity of 87.2% and a specificity of 80.4%. Unique significant risk factors of CA were increasing severity of affective episodes (odds ratio (OR) = 28.8), BD II (OR = 3.3), hypomanic/manic episode induced by an antidepressant and/or alcohol (OR = 3.3), and female gender (OR = 3.1). CONCLUSION: The clinical factors associated with CA may help targeting patients with BD with a course aggravation, and are in line with previously reported neuropathological processes of illness progression.

Regional cortical thinning may be a biological marker for borderline personality disorder.

OBJECTIVE: We investigated cerebral cortical thickness and its relation to measurements of difficulties with identifying and describing emotions in patients with borderline personality disorder (BPD). METHOD: Eighteen SCID-II-diagnosed female patients with BPD and 21 healthy female controls underwent magnetic resonance imaging and completed the Toronto Alexithymia Scale (TAS). First, regional cortical thickness across the cerebral surface was compared between patients and healthy controls. Then, analyses of the association between cortical thickness and TAS subscales were performed in patients. RESULTS: Compared with controls, patients exhibited clusters of significantly reduced cortical thickness in the left medial and lateral prefrontal cortex, left temporoparietal junction, bilateral temporal poles, and bilateral paracentral lobules. Significant negative associations were observed between cortical thickness and the 'Difficulties Describing Feelings' TAS subscale (DDF) scores in patients. The anatomical distribution of these associations was highly overlapping with the group differences in cortical thickness. CONCLUSION: The pattern of regions exhibiting cortical thinning in patients resembles a network of cortical structures repeatedly shown to be involved in social cognition. The results of the DDF analyses suggest that the thinning may partly be related to interpersonal dysfunction in patients with BPD. The pattern of thinning may represent a potential biological marker for BPD.

Psychological distress after recent detection of fetal malformation: short-term effect on second-trimester uteroplacental and fetoplacental circulation.

We examined the short-term effect of severe maternal psychological distress on the placental circulation in second trimester in a prospective observational study. In 86 pregnant women with a newly detected fetal malformation, and 98 women with normal ultrasound findings, distress was assessed using the Impact of Event Scale and the General Health Questionnaire-28. Uterine and umbilical artery pulsatility indices, notching and heart rates were measured by Doppler ultrasound. Psychological distress was high in the anomaly group, but circulatory outcome measures did not differ between groups. Multiple regression analyses did not show an increase in circulatory resistance measures even at high distress levels.

Temperament and character in patients with bipolar II disorder and recurrent brief depression.

OBJECTIVES: We compared the temperament and character profiles of 21 patients with bipolar II disorder, 40 patients with recurrent brief depression (RBD; at least monthly depressive episodes meeting the diagnostic criteria for major depressive episode except for duration that is less than 2 weeks, typically 2-3 days, without fixed relation to menstrual cycle) of which 21 had no history of hypomania and 19 had experienced hypomanic episodes, and 21 age- and sex-matched controls. METHODS: Assessments included the Montgomery-Åsberg Depression Rating Scale, Hypomania Checklist, and Temperament and Character Inventory-125. Patients with cluster A and B personality disorders were excluded. RESULTS: Bipolar II and RBD patients had higher harm avoidance (HA) and lower self-directedness (SD) compared with controls. Excluding panic disorder comorbidity effaced this difference in HA and SD (bipolar II only) and harm avoidance. No other differences were found. CONCLUSIONS: In this first study comparing personality profiles of patients with bipolar II vs RBD, when controlling for confounders, neither bipolar II nor RBD patients differed significantly from healthy controls. The lower SD scores among RBD patients may reflect sampling bias (a higher rate of Axis 2 cluster C disorders).

Acute maternal social dysfunction, health perception and psychological distress after ultrasonographic detection of a fetal structural anomaly.

OBJECTIVES: To predict acute psychological distress in pregnant women following detection of a fetal structural anomaly by ultrasonography, and to relate these findings to a comparison group. DESIGN: A prospective, observational study. SETTING: Tertiary referral centre for fetal medicine. POPULATION: One hundred and eighty pregnant women with a fetal structural anomaly detected by ultrasound (study group) and 111 with normal ultrasound findings (comparison group) were included within a week following sonographic examination after gestational age 12 weeks (inclusion period: May 2006 to February 2009). METHODS: Social dysfunction and health perception were assessed by the corresponding subscales of the General Health Questionnaire (GHQ-28). Psychological distress was assessed using the Impact of Events Scale (IES-22), Edinburgh Postnatal Depression Scale (EPDS) and the anxiety and depression subscales of the GHQ-28. Fetal anomalies were classified according to severity and diagnostic or prognostic ambiguity at the time of assessment. MAIN OUTCOME MEASURES: Social dysfunction, health perception and psychological distress (intrusion, avoidance, arousal, anxiety, depression). RESULTS: The least severe anomalies with no diagnostic or prognostic ambiguity induced the lowest levels of IES intrusive distress (P = 0.025). Women included after 22 weeks of gestation (24%) reported significantly higher GHQ distress than women included earlier in pregnancy (P = 0.003). The study group had significantly higher levels of psychosocial distress than the comparison group on all psychometric endpoints. CONCLUSIONS: Psychological distress was predicted by gestational age at the time of assessment, severity of the fetal anomaly, and ambiguity concerning diagnosis or prognosis.

The phenomenology of recurrent brief depression with and without hypomanic features.

BACKGROUND: The nosologic status of recurrent brief depression (RBD) is debated. We studied the phenomenology of RBD in a clinical sample of outpatients. METHODS: Forty patients (mean age 33; 73% females) and 21 age- and gender-matched mentally healthy controls were examined (clinical interview, M.I.N.I. neuropsychiatric interview, MADRS, Stanley Foundation Network Entry Questionnaire). Exclusion criteria were bipolar I or II disorders, a history of psychosis, concurrent major depressive episode, organic brain or personality disorders (clusters A and B). RESULTS: The mean age of onset of RBD was 20 years with a mean of 14 episodes/year with brief (mean 3 days) severe depressive episodes. Nineteen (47%) reported additional short episodes of brief hypomania (>1 day duration; RBD-H) of which nine (23%) never had experienced a major depression. Twenty-one (53%) patients reported RBD only (RBD-O) with or without (n=12) past history of major depression or dysthymia. During the last depressive episode, 76% of the RBD-O and 90% of the RBD-H patients had a melancholic depression. Seventy-one % of the RBD-O and 79% of the RBD-H reported at least two out of three atypical symptoms. Nineteen (48%) of the patients reported anger attacks and panic disorder, the latter being more prevalent in the RBD-H subgroup (68% versus 29%, p=0.012). LIMITATIONS: Cross-sectional study of self-referrals or patients referred by primary care physicians or psychiatrists. CONCLUSIONS: The study supports the validity of RBD as a disorder separate from bipolar II, cyclothymia and recurrent major depression. A brief episode of hypomanic symptoms is a severity marker of RBD.

Psychological distress in mothers and fathers of preschool children: a 5-year follow-up study after birth.

OBJECTIVE: Maternal and paternal psychological distress influence children's development and health beyond the perinatal period. The aim of our study was to describe psychological health during a 5-year period in parents of preschool children. Secondarily, we wanted to explore differences between mothers and fathers and identify predictors for increased psychological distress in parents. DESIGN: Prospective cohort study. SETTING: A county in Southern Norway 1998-2004. POPULATION: One hundred and twenty-three mothers and 112 fathers were candidates for the follow-up study. METHODS: Parental psychological responses were assessed using the General Health Questionnaire (GHQ-28), State Anxiety Inventory-X1 and Impact of Event Scale at 0-4 days, 6 weeks, 6 months and 5 years after delivery of a healthy child. MAIN OUTCOME MEASURE: Parental psychological distress defined by GHQ-28 Likert sum score at 5-year follow-up. RESULTS: Clinically important psychological distress (GHQ case score > or = 6) was reported by more mothers (29%) than by fathers (11%) (P = 0.004). In multivariate analysis, psychological distress (GHQ-28 Likert sum score) after 5 years was predicted by initial psychological distress, being single and low educational level in mothers, and unemployment and low quality of relationship with partner in fathers. CONCLUSIONS: Fathers reported significantly lower frequency of clinically important psychological distress and more stable scores than mothers throughout the period. The results indicate that selected psychometric screening may be warranted for parents with known psychosocial risk factors.

Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia.

The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a 'good effect' of long-term BTX treatment (n = 47), had significantly lower median TWSTRS total score, and a 3x lower frequency of high HAD-D scores, than those evaluated to an 'unsatisfactory effect' (n = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms.

Prenatal diagnosis of congenital malformations and parental psychological distress--a prospective longitudinal cohort study.

OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.

Does guilt proneness predict acute and long-term distress in relatives of patients with schizophrenia?

OBJECTIVE: The aim of the study was to improve our understanding of guilt proneness as predictor of acute and long-term stress responses in relatives of acutely admitted patients. METHOD: Forty-nine relatives in close contact with 36 patients suffering from schizophrenia DSM-III-R, completed Hostility Guilt (HG) and Guilt Conscience (GC) scales (Revised Mosher Guilt Inventory), and Levenson's Locus of Control Scale (LOC) at the patient's admission to hospital, and the General Health Questionnaire (GHQ) at the patient's admission and at 9 months after discharge. RESULTS: Acute distress (GHQ) was positively related to HG, but not when controlling for LOC. GC was positively associated with acute and long-term distress, GHQ-depression and coping-failure, and long-term GHQ-anxiety. When controlling for LOC, GC was still positively related to long-term distress. HG, GC and LOC explained 32% variance of GHQ at 9 months. CONCLUSION: GC seems to be an important predictor of long-term distress in relatives.