High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

The bidirectional impact of perceived and enacted support on mood in bipolar outpatients: A two-year prospective study.

Bipolar disorder (BD) is a chronic illness, and a great need has been expressed to elucidate factors affecting the course of the disease. Social support is one of the psychosocial factors that is assumed to play an important role in the course of BD, but it is largely unknown whether the depressive and/or manic symptoms also affect the patients' support system. Further, the perception of one's social support appears to have stronger effects on disease outcomes than one's enacted or received support, but whether this also applies to BD has not been investigated. The objective of this study is to examine temporal, bidirectional associations between mood states (depression and mania) and both enacted and perceived support in BD patients. The current study was conducted among 173 BD I and II outpatients, with overall light to mild mood symptoms. Severity of mood symptoms and social support (enacted as well as perceived) were assessed every 3months, for 2years (1146 data points). Multilevel regression analyses (linear mixed-models) showed that lower perceived support during 3months was associated with subsequent higher levels of depressive, but not of manic symptoms in the following 3months. Vice versa, depressive symptoms during 3months were associated with less perceived support in the following 3months. Further, manic symptoms during 3months were associated with less enacted support in the subsequent 3 months. The current study suggests that perceived, but not enacted, support is consistently related to depressive symptoms in a bidirectional way, while mania is specifically associated with a subsequent loss of enacted support. Clinical implications of the current findings are discussed.

The use of the prospective NIMH Life Chart Method as a bipolar mood assessment method in research: a systematic review of different methods, outcome measures and interpretations.

BACKGROUND: The severity of bipolar disorder can be assessed using the daily prospective National Institute of Mental Health׳s Life Chart Method (LCM-p). Also for scientific research the LCM-p, has been used frequently. However, processing and analyzing the LCM-p for research purposes, are challenging because of the multitude of complex measures that can be derived from the data. In the current paper we review the different LCM-p course variables (mood episodes, average severity, proportion of time ill and mood switches) and their definitions. Strengths and limitations and the impact of the use of different LCM-p course measures and definitions on the research results are described. METHOD: A systematic review of original papers on the LCM was conducted using 9 electronic databases for literature between January 1996 and December 2014. Papers using other prospective charting procedures were not evaluated in the current study. RESULTS: The initial literature search led to 1352 papers of which 21 were eventually selected. A relatively wide variety of definitions of LCM-p course variables was used across the studies. Especially for the calculation of number of episodes and mood switch no univocal definition seems to exist. Across studies several different durations and severity criteria are applied to calculate these variables. We describe which variables and definitions are most suitable for detecting specific bipolar disease course characteristics and patterns. CONCLUSION: In the absence of a golden standard for the calculation of LCM-p course variables, researchers should report the exact method they applied to their LCM-p data, and clearly motivate why this is their method of first choice considering their research aim.

Stressful life events in bipolar I and II disorder: cause or consequence of mood symptoms?

BACKGROUND: Life events are assumed to be triggers for new mood episodes in bipolar disorder (BD). However whether life events may also be a result of previous mood episodes is rather unclear. METHOD: 173 bipolar outpatients (BD I and II) were assessed every three months for two years. Life events were assessed by Paykel׳s self-report questionnaire. Both monthly functional impairment due to manic or depressive symptomatology and mood symptoms were assessed. RESULTS: Negative life events were significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction (life events as a result of mood/functional impairment), we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events. LIMITATIONS: The use of a self-report questionnaire for the assessment of life events makes it difficult to determine whether life events are cause or consequence of mood symptoms. Second, the results can only be generalized to relatively stable bipolar outpatients, as the number of severely depressed as well as severely manic patients was low. CONCLUSIONS: Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.

Two-year follow-up of a randomized controlled trial of stepped care cognitive behavioral therapy to prevent recurrence of depression in an older population.

OBJECTIVE: This study aims to determine the long-term effect of a stepped care cognitive behavioral therapy prevention program for depression in older people and the factors predicting or moderating outcome. METHODS: In a randomized controlled trial, 136 participants, aged 55 years or older, who had been treated for depression, received during 12 months a stepped care program (SCP) or care as usual (CAU) and were then followed up for a second year. Outcome was defined as the start of a new mental health treatment for depression in a specialized outpatient setting, as recorded in the patients' electronic medical records. RESULTS: Of the 123 patients, 38 required new mental health treatment. Survival analysis showed that participants in SCP (n = 27) required new treatment significantly more than patients receiving CAU (n = 11). Negative life events in the last year were predictive for new treatment in CAU but not in SCP. CONCLUSIONS: An SCP seems to lower the threshold for new specialized mental health treatment for depression, whereas new treatment in CAU patients occurs more often in reaction to recent life events.

Glucocorticoid and mineralocorticoid receptor polymorphisms and clinical characteristics in bipolar disorder patients.

INTRODUCTION: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD. METHODS: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N363S, BclI, and 9ß polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics. RESULTS: Seasonal patterns of hypomania are related to the BclI haplotype and the TthIIII+9ß haplotype of the GR gene (respectively, crude p=.007 and crude p=.005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p=.004, after adjustment p=.016). No evidence for a role of the MR in modifying clinical manifestations was found. CONCLUSION: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset.

Seasonality of mood disorders in adults with lifetime attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: The objective of this study was to estimate the prevalence of Seasonal Affective Disorder (SAD) in adults with lifetime Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD: Patients eligible for this study had lifetime impairing symptoms of ADHD and a current and/or past co-morbid mood disorder according to their medical record. The Seasonal Pattern Assessment Questionnaire (SPAQ) was administered by a telephone interview to assess seasonality. RESULTS: The overall rate of SAD in this clinical population of adults with ADHD was estimated at 27%. Females were more at risk to develop SAD than men. LIMITATIONS: The SPAQ is a screening, not a diagnostic instrument. CONCLUSIONS: SAD symptoms are frequently comorbid with ADHD in adults. These results have clinical relevance for the recognition and treatment of SAD with bright light therapy in adults with ADHD.

A 3.5-year naturalistic follow-up study of depressed out-patients.

Outcome studies of patients suffering from depression indicate high relapse rates and a tendency towards chronicity. The present study describes the long-term outcome of 95 depressed outpatients in a third-level referral centre. and examines the relationship between baseline-variables (age, sex, level of psychopathology, age at onset of first psychiatric disorder, duration of illness at baseline, diagnosis) and outcome variables. After 3.5 years, 34 patients (36%) had a chronic course, 24 patients (25%) had at least one recurrence and 37 patients (39%) had a non-recurrent course. Chronicity was significantly correlated with an early age of onset of the first psychiatric disorder, a high level of psychopathology and a high level of depressive symptoms at baseline. The duration of depression at index did not differentiate chronic course from recurrent or non-recurrent course. After 1 year of follow-up, patients with recurrence were significantly more likely to stop antidepressant treatment. The results confirm the great chance for chronicity and recurrence in depression and the need to develop long-term treatment programs to prevent relapse.

Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.

BACKGROUND: A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. METHODS: Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). RESULTS: An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. CONCLUSIONS: In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.

Lithium augmentation of venlafaxine: an open-label trial.

The authors conducted an open-label study of the efficacy and tolerability of venlafaxine and of lithium augmentation in outpatients with depression who were not responding to venlafaxine. Outpatients aged 18 to 70 years were eligible if they had a minimum baseline score of 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were started on venlafaxine 37.5 mg twice daily for 1 week. For weeks 2 through 4, the dose of venlafaxine was increased to 75 mg twice daily, and for weeks 5 through 7, the dose was further increased to 75 mg three times daily. At the end of the 7-week treatment period, patients with a <50% decrease in their HAM-D scores from baseline were given lithium carbonate 600 mg once daily. The dose of lithium carbonate was adjusted to maintain plasma levels in the range of 0.6 to 1.0 mmol/mL. Efficacy was assessed with the 17-item HAM-D, Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions Scale. Data were analyzed on an intent-to-treat basis. At the end of the 7-week treatment period, 35% of patients showed a > or = 50% decrease in their HAM-D scores from baseline. Lithium augmentation was initiated in 23 patients. The results showed that the addition of lithium was well-tolerated and led to a further decrease in the HAM-D scores, with eight patients responding and two of them presenting a remission. The addition of lithium to venlafaxine was found to be a well-tolerated strategy in treatment-resistant patients.

Venlafaxine serum levels and CYP2D6 genotype.

Thirty-three patients with depression treated with 225 mg venlafaxine were genotyped for the polymorphic enzyme, debrisoquine 4-hydroxylase (CYP2D6). The relationship between drug and metabolite levels and between genotype and clinical response were investigated. Although the number of responders in this study is insufficient for definite conclusions to be drawn, a target therapeutic concentration ranging from 195-400 microg/L for the sum of venlafaxine and O-desmethylvenlafaxine is suggested. The ratio of O-desmethylvenlafaxine to venlafaxine in the serum concentrations is a measure of metabolic turnover, and can be used to distinguish between ultrarapid and poor metabolizers. All but one of the nonresponders in this study had lower ratios than the responders. Three patients (9%) had homozygous defective CYP2D6 alleles and did not readily metabolize venlafaxine to O-desmethylvenlafaxine, pointing to poor metabolism. In these patients, N-desmethylation was increased. Two out of four patients detected by the ratio as potentially ultrarapid metabolizers were shown to have multiple copies of a functional CYP2D6 gene.

A comparison of the 'Hamilton Rating Scale for Depression' and the 'Montgomery-Asberg Depression rating Scale'.

Although the Hamilton Rating Scale for Depression (HRSD) is the most frequently used rating scale for quantifying depressive states, it has been criticized for its reliability and its usability in clinical practice. This criticism is less applying to the Montgomery-Asberg Depression Rating Scale (MADRS). Goal of the present study is to investigate the reliability and validity, and clinical relationship between the HRSD and the MADRS. For 60 out-patients with diagnosed depression (DSM IV296.2x, 296.3x, 300.40 and 311.00), the HRSD and MADRS were scored at baseline and 6 weeks later by an independent rater according to a structured interview. Also the Clinical Global Impression (CGI) was assessed by a psychiatrist. Satisfying agreement was found between the totalscores (r= .75, p>.000 en r=.92, p>.000 respectively, at baseline and 6 weeks later). Furthermore agreement was found between the items of both scales, and these agree with the clinical impression. The reliability of the MADRS is more stable than the reliability of the HRSD (α = .6367 and α =.8900 vs α = .2193 and α = .8362 at baseline and at endpoint respectively). Considering the ease of scoring both scales in one interview and the widely international use of the HRSD, scoring both the HRSD and the MADRS to measure the severity of a depression seems to be an acceptabel covenant.

Predictability of dropout in unipolar depressed outpatients.

In a three phase sequential treatment strategy study involving 119 depressed outpatients, a total of 31 patients (26.7%) stopped treatment prematurely due to side-effects (21/31), aggravation of symptoms (3/31), non-compliance (4/31), and non-treatment related events (3/31). At baseline, no significant differences were found on sociodemographic and psychiatric data between patients who did or did not drop out. As predictors of dropout eight domains of data concerning psychiatric history, premorbid history, symptomatology, personality, and social adjustment were used. Using a logistic linear regression analysis, only three variables were related to dropout. Patients with a history of alcohol use or poor social functioning according to axis V of the Diagnostic and Statistical Manual (DSM)-III-R had a higher chance to drop out, while patients with a sleep disturbance according to the Symptom Checklist (SCL)-90 had a smaller chance to drop out.

Predictors of (non-) response in depressed outpatients treated with a three-phase sequential medication strategy.

The predictive value of eight domains or sets of variables including sociodemographic aspects, premorbid history, symptomatology, personality, social and diagnostic data are evaluated in depressed outpatients with a Hamilton Rating Scale for Depression (HRSD) score of at least 14. Patients were treated using a three-phase sequential treatment strategy. Of the 119 patients, 88 completed the trial. The HRSD-score at the end of phases I, II or III was used as an outcome measure. Patients with an initially high HRSD-score and an obsessive-compulsive personality had a greater chance of recovery, while patients with somatization and a passive-aggressive personality had less of a chance of recovery. Variables involving psychiatric history, premorbid history or symptomatology of the depression, were not significantly related to outcome. The endogenous/non-endogenous distinction was not a predictor of response.

Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients.

Depressed outpatients (n = 51) resistant to treatment with maprotiline were treated in a blind, randomized, single-centre study, for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor (MAO-A-I), brofaromine or lithium addition to maprotiline. The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period. No significant differences in efficacy were found between the two treatment regimes. In the patients who completed the trial, brofaromine was well tolerated with the exception of insomnia. Anticholinergic effects as well as thyroid dysfunctions (17 out of 20) were more frequent in the maprotiline/lithium group.