Arne E. Vaaler

Which clinical and experimental data link temporal lobe epilepsy with depression

The association of temporal lobe epilepsy with depression and other neuropsychiatric disorders has been known since the early beginnings of neurology and psychiatry. However, only recently have in vivo and ex vivo techniques such as Positron Emission Tomography, Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in combination with refined animal models and behavioral tests made it possible to identify an emerging pattern of common pathophysiological mechanisms. We now have growing evidence that in both disorders altered interaction of serotonergic and noradrenergic neurons with glutamatergic systems is associated with abnormal neuronal circuits and hyperexcitability. Neuronal hyperexcitability can possibly evoke seizure activity as well as disturbed emotions. Moreover, decreased synaptic levels of neurotransmitters and high glucocorticoid levels influence intracellular signaling pathways such as cAMP, causing disturbances of brain‐derived and other neurotrophic factors. These may be associated with hippocampal atrophy seen on Magnetic Resonance Imaging and memory impairment as well as altered fear processing and transient hypertrophy of the amygdala. Positron Emission Tomography studies additionally suggest hypometabolism of glucose in temporal and frontal lobes. Last, but not least, in temporal lobe epilepsy and depression astrocytes play a role that reaches far beyond their involvement in hippocampal sclerosis and ultimately, therapeutic regulation of glial‐neuronal interactions may be a target for future research. All these mechanisms are strongly intertwined and probably bidirectional such that the structural and functional alterations from one disease increase the risk for developing the other. This review provides an integrative update of the most relevant experimental and clinical data on temporal lobe epilepsy and its association with depression.

Actigraphic assessment of motor activity in acutely admitted inpatients with bipolar disorder

Introduction Mania is associated with increased activity, whereas psychomotor retardation is often found in bipolar depression. Actigraphy is a promising tool for monitoring phase shifts and changes following treatment in bipolar disorder. The aim of this study was to compare recordings of motor activity in mania, bipolar depression and healthy controls, using linear and nonlinear analytical methods. Materials and Methods Recordings from 18 acutely hospitalized inpatients with mania were compared to 12 recordings from bipolar depression inpatients and 28 healthy controls. 24-hour actigraphy recordings and 64-minute periods of continuous motor activity in the morning and evening were analyzed. Mean activity and several measures of variability and complexity were calculated. Results Patients with depression had a lower mean activity level compared to controls, but higher variability shown by increased standard deviation (SD) and root mean square successive difference (RMSSD) over 24 hours and in the active morning period. The patients with mania had lower first lag autocorrelation compared to controls, and Fourier analysis showed higher variance in the high frequency part of the spectrum corresponding to the period from 2–8 minutes. Both patient groups had a higher RMSSD/SD ratio compared to controls. In patients with mania we found an increased complexity of time series in the active morning period, compared to patients with depression. The findings in the patients with mania are similar to previous findings in patients with schizophrenia and healthy individuals treated with a glutamatergic antagonist. Conclusion We have found distinctly different activity patterns in hospitalized patients with bipolar disorder in episodes of mania and depression, assessed by actigraphy and analyzed with linear and nonlinear mathematical methods, as well as clear differences between the patients and healthy comparison subjects.

Risk factors related to lifetime suicide attempts in acutely admitted bipolar disorder inpatients

Finseth PI, Morken G, Andreassen OA, Malt UF, Vaaler AE. Risk factors related to lifetime suicide attempts in acutely admitted bipolar disorder inpatients. 
Bipolar Disord 2012: 14: 727–734.

Effects of different interior decorations in the seclusion area of a psychiatric acute ward

The objective of the study was to compare development in symptoms, behaviours, treatment and patient satisfaction of a traditional interior and an interior furnished like an ordinary home in a seclusion area. A naturalistic sample of 56 consecutive patients admitted to an acute ward was allocated to two different seclusion areas, one with a traditional interior and one decorated as an ordinary home. Symptoms of psychopathology, therapeutic steps taken, violent episodes, length of patient stay and patient satisfaction were recorded. There were no differences in changes in scores on The Positive and Negative Syndrome Scale for schizophrenia, The Brøset Violence Checklist or the Global Assessment of Function split version scale between the two patient groups. Therapeutic steps taken, number of violent episodes and length of patient stay was also similar. Female patients preferred an ordinary home interior. It was concluded that interior and furnishing like an ordinary home in the seclusion areas created an environment with comparable treatment outcomes to the traditional dismal interior, and had positive effects on many patients’ well-being, at least among the women. The traditional beliefs that a sparsely decorated interior is a method to reduce symptoms of psychopathology and dangerous behaviours were not supported by our data.

Age at onset of first episode and time to treatment in in-patients with bipolar disorder.

This study aimed to investigate the relationship between age at onset and time to first pharmacological treatment in patients with either bipolar I or II disorder. A total of 146 consecutive in-patients acutely admitted from the same catchment area were included. Patients were divided into four age groups: 0-12 years (23%); 13-18 years (32%); 19-29 years (26%); and > or =30 years (18%). Mean age at first affective episode was 20.2 years (s.d.=11.8). This represents a similar pattern to the age at onset seen in out-patients in the USA. Early age at onset predicted a longer time to first pharmacological treatment (rho =-0.695, P<0.01).

Short-term prediction of threatening and violent behaviour in an Acute Psychiatric Intensive Care Unit based on patient and environment characteristics

BackgroundThe aims of the present study were to investigate clinically relevant patient and environment-related predictive factors for threats and violent incidents the first three days in a PICU population based on evaluations done at admittance.MethodsIn 2000 and 2001 all 118 consecutive patients were assessed at admittance to a Psychiatric Intensive Care Unit (PICU). Patient-related conditions as actuarial data from present admission, global clinical evaluations by physician at admittance and clinical nurses first day, a single rating with an observer rated scale scoring behaviours that predict short-term violence in psychiatric inpatients (The Brøset Violence Checklist (BVC)) at admittance, and environment-related conditions as use of segregation or not were related to the outcome measure Staff Observation Aggression Scale-Revised (SOAS-R). A multiple logistic regression analysis with SOAS-R as outcome variable was performed.ResultsThe global clinical evaluations and the BVC were effective and more suitable than actuarial data in predicting short-term aggression. The use of segregation reduced the number of SOAS-R incidents.ConclusionsIn a naturalistic group of patients in a PICU segregation of patients lowers the number of aggressive and threatening incidents. Prediction should be based on clinical global judgment, and instruments designed to predict short-term aggression in psychiatric inpatients.Trial registrationsNCT00184119/NCT00184132

Bipolar disorder patients have similar levels of education but lower socio-economic status than the general population

BACKGROUND There is conflicting evidence regarding the educational level and its importance for social and occupational functioning in bipolar disorder (BD). The aim of this study was to investigate how educational achievement relates to function in BD compared with the general population, and which clinical factors are associated with level of education. METHODS Hospitalized patients with DSM-IV BD (N=257; 69.3% BD I; 25.7% BD II; 5.1 BD NOS; 51.4% females) were consecutively recruited from mental health clinics throughout Norway and compared with a geographically matched reference sample from the general population (N=56,540) on levels of education, marital status, income, and disability benefits. Further analyses of association were carried out using logistic regression analyses. RESULTS A significantly higher proportion of subjects in the BD group than in the reference group was single, had low income, or was disabled. No between-group difference was found in educational level. In the reference group education was inversely correlated with the risk of being disabled, but no such relationship was found in the BD group. Rapid cycling and recurring depressive episodes were the only clinical characteristics associated with low educational level. LIMITATIONS Acutely admitted patients might not be representative for milder forms of disease. CONCLUSIONS Despite similar levels of education, BD patients had lower social and occupational function than the general population, and no association was found between education and disability for BD patients.

Substance use at admission to an acute psychiatric department

Substance use is prevalent in patients with psychiatric disorders and may cause severe symptoms in addition to complicating the diagnosis of psychiatric disorders. The aims of the study were to find the prevalence in use of alcohol, drugs, benzodiazepines, hypnotics, opiates and stimulants, and to find the prevalence of substance use disorders at admission to an acute psychiatric department receiving all admissions from a catchment area. Patients were interviewed about use of medications and intoxicating substances during the last week before admission in 227 consecutive admissions. Urine samples were analysed with the liquid chromatography with mass spectrometry (LC-MS) method. Use of substances was determined from reported use and findings in urine samples. Diagnoses were set at discharge according to ICD-10 research criteria. In 81.9% of the admissions, the patient had used alcohol, drugs, benzodiazepines, hypnotics, opiates or stimulants prior to admission. More men used alcohol, cannabis and stimulants, whereas more women used benzodiazepines. In 31.7% of the admissions, 49.5% of men and 16.4% of women, the patients had a substance use disorder (ICD-10, F10–19). Patients with substance use disorders had a shorter stay in hospital than other patients, and patients with no psychiatric disorder other than substance use disorders had a median length of stay of 2 days. Most patients had used psychoactive substances before admission to the acute psychiatric department, and half of the men had a substance use disorder.

The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder

BackgroundThe treatment of depressive phases of bipolar disorder is challenging. The effects of the commonly used antidepressants in bipolar depression are questionable. Electroconvulsive therapy is generally considered to be the most effective treatment even if there are no randomized controlled trials of electroconvulsive therapy in bipolar depression. The safety of electroconvulsive therapy is well documented, but there are some controversies as to the cognitive side effects. The aim of this study is to compare the effects and side effects of electroconvulsive therapy to pharmacological treatment in treatment resistant bipolar depression. Cognitive changes and quality of life during the treatment will be assessed.Methods/DesignA prospective, randomised controlled, multi-centre six- week acute treatment trial with seven clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks). A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used. Setting: Nine study centres across Norway, all acute psychiatric departments. Sample: n = 132 patients, aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, Montgomery Åsberg Depression Rating Scale Score of at least 25 at baseline. Intervention: Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual.DiscussionThis study is the first randomized controlled trial that aims to investigate whether electroconvulsive therapy is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry.Trial registrationNCT00664976

The Effect of Electroconvulsive Therapy on Neurocognitive Function in Treatment-Resistant Bipolar Disorder Depression

OBJECTIVE To compare the effects of right unilateral (RUL) electroconvulsive therapy (ECT) and algorithm-based pharmacologic treatment (APT) on neurocognitive function in treatment-resistant bipolar disorder depression. METHOD Inpatients with DSM-IV-TR-diagnosed, treatment-resistant bipolar depression, who were acutely admitted to 1 of the 7 clinical study centers in Norway, were recruited from May 2008 to April 2011 into a prospective, randomized controlled, 6-week acute treatment trial. General neurocognitive function was assessed with the MATRICS Consensus Cognitive Battery (MCCB), and retrograde memory for autobiographical events was assessed with the Autobiographical Memory Interview-Short Form (AMI-SF) before and shortly after (mean = 23.5 days) a trial with either RUL brief-pulse ECT (mean dose = 233.3 mC) or APT. RESULTS Seventy-three patients entered, and 39 (nECT = 19, nAPT = 20) completed. Both groups showed improvements in all MCCB domain scores, with no significant differences between the study groups (no interaction effect: F₁,₃₇ = 1.52, P = NS). Improvements in neurocognitive performance were significantly correlated with reductions in depression ratings posttreatment. The AMI-SF score was significantly lower (based on consistent answers from pre- to posttreatment) in the ECT group (72.9%) than in the APT group (80.8%, P = .025), indicating reduced consistency in autobiographical memory after ECT. CONCLUSIONS General neurocognitive function was unaffected by RUL brief-pulse ECT treatment and positively related to improved mood in bipolar depression. Autobiographical memory consistency was reduced in patients treated with ECT. The results suggest that ECT can be used in treatment-resistant bipolar depression without compromising general neurocognitive function. The clinical relevance of reduced autobiographical memory consistency in the ECT group requires further investigation. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00664976.