Jens Knud Larsen

Selective ablations within the prefrontal cortex of the rat and performance of delayed alternation

Ablations of the pregenual area of the anteromedial prefrontal cortex produced a significantly larger impairment in delayed alternation than did removal of the supragenual area. Both ablations caused significant impairments as compared with lesions of the posteromedial cortex. Only one of four rats with ablations of the dorsal bank and lip of the anterior part of the rhinal sulcus was impaired. The results indicate than in the rat, as in the monkey and dog, one part of the prefrontal cortex is particularly involved in mediation of delayed alternation.

Reverse Trendelenburg position reduces intracranial pressure during craniotomy.

Cerebral swelling and herniation pose serious surgical obstacles during craniotomy for space-occupying lesions. Positioning patients head-up has been shown previously to reduce intracranial pressure (ICP) in neurotraumatized patients, but has not been investigated during intracranial surgery. The current study examined the effects of 10-deg reverse Trendelenburg position (RTP) on ICP and cerebral perfusion pressure (CPP). Forty adult patients subjected to craniotomy for supratentorial tumors were given standardized propofol–fentanyl–cisatracurium general anesthesia and were moderately hyperventilated. In 26 of 40 patients with expected poor clinical outcome, an additional catheter was placed in the internal jugular bulb to determine internal jugular bulb pressure (JBP). ICP was determined by subdural measurement using a 22-gauge needle advanced through the dura after removal of the bone flap. ICP was referenced to the level of the dural incision. ICP, mean arterial blood pressure, and CPP were compared with repeat measurements 1 minute after RTP. The tension of the dura was graded qualitatively by the surgeon by digital palpation and was compared to post-RTP. ICP decreased from 9.5 mm Hg to 6.0 mm Hg (P < .001; all values are median) within 1 minute after 10-deg RTP. Mean arterial blood pressure decreased from 82.0 mm Hg to 78.5 mm Hg (P < .001). CPP was unchanged (70.5 mm Hg versus 71 mm Hg after RTP), whereas JBP decreased from 8 mm Hg to 4 mm Hg (P < .001). High initial ICP was correlated to the greatest magnitude of decrease in ICP. No significant correlation was found between change in ICP and change in JBP. Intracranial pressue after RTP resulted in decreased tension of the dura. RTP appears to be an effective means of reducing ICP during craniotomy, thereby reducing the risk of cerebral herniation. CPP is not affected. Studies over longer periods of time are warranted, however.

The stability of the Seasonal Pattern Assessment Questionnaire score index over time and the validity compared to classification according to DSM-III-R

BACKGROUND In 1984, Rosenthal et al. described a group of patients characterised by repeated winter depression with atypical symptoms eventually followed by summer mania or hypomania (seasonal affective disorder, SAD). The relationship between SAD and the classical manic-depressive disorder is uncertain. The aim of this study was to validate the Seasonal Pattern Assessment Questionnaire (SPAQ) classification in relation to the DSM-III-R criteria of seasonal patterns in a group of patients with bipolar affective disorder and to evaluate the stability of the SPAQ score index over time. METHODS A group of bipolar patients were followed for 3 years with examinations every third month and at hospitalisation. At inclusion and at each following examination the patients were rated with the Hamilton Depression Rating Scale, the Newcastle Depression Rating Scale, and the Bech-Rafaelsen Mania Rating Scale. At inclusion and once a year the patients completed the SPAQ. RESULTS Fifty-six patients agreed to participate and 46 patients completed 1 year or more. Eight patients, all women, had at least one SPAQ score index (SSI) of 11 or more. Women scored significantly higher than men on SPAQ. The test/re-test reliability of SSI between two consecutive years was good, but decreased as the time difference between tests increased. Moreover, we found no relation between seasonal variations of affective episodes according to SSI and DSM-III-R. LIMITATIONS The group of patients with seasonality according to DSM-III-R or SSI was small. CONCLUSION The validity of SSI between two consecutive years is good, but decreases as the time difference between tests increases. There is no relationship between seasonality defined by DSM-III-R and SSI. Female bipolar patients show, as the general population, seasonal variations in mood, energy, sociality, appetite, and sleep independently of their affective episodes. SSI cannot be used for the prediction of seasonal variation in a group of bipolar patients.

Prematurity and low birth weight as risk factors for the development of affective disorder, especially depression and schizophrenia: A register study

Larsen JK, Bendsen BB, Foldager L, Munk-Jørgensen P. Prematurity and low birth weight as risk factors for the development of affective disorder, especially depression and schizophrenia: a register study. Background: The present study examined whether low birth weight, prematurity or low birth weight adjusted for gestational age are risk factors for the subsequent development of affective disorder, especially depression. Methods: A population-based case–control design was applied to the Danish Medical Birth Register and the Danish Psychiatric Central Register to identify all individuals born between 1 January 1974 and 31 December 1990 and diagnosed prior to 29 August 2003 with affective disorder alone (ICD-10 F3; 4297 females, 1861 males), schizophrenia alone (ICD-10 F2; 1364 females, 2292 males) or both disorders (ICD-10 F3 + F2; 450 females, 405 males). The association between low birth weight and the risk of developing affective disorder and/or schizophrenia was analysed by conditional logistic regression analysis. Results: Low birth weight was found to be associated with a significantly elevated risk of developing schizophrenia alone (p = 0.021) and both affective disorder and schizophrenia (p = 0.024), and a non-significantly elevated risk of developing affective disorder alone (p = 0.063). The effect remained significant in the affective disorder and schizophrenia groups (p = 0.039) when correcting for gestational age (premature birth), but was lost in the group with both disorders. Premature birth per se was found to be associated with a significantly elevated risk of developing both affective disorder and schizophrenia (p = 0.00018), an effect that remained significant after adjustment for low birth weight. Conclusion: Prematurity and low birth weight were found to be risk factors for subsequent development of affective disorder (especially depression) and schizophrenia.

Climatic factors and bipolar affective disorder

In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases. A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D17), and the Bech–Rafaelsen Mania Rating Scale (MAS). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D17 score of 12 or more (depression)] and any meteorological parameters. We found a statistical significant correlation between mean HAM-D17 scores and change in mean and maximum temperature, and non-statistical significant correlations between mean MAS scores and rainfall plus atmospheric pressure, and non-statistical significant correlations between mean HAM-D17 scores and hours of sunshine and cloudiness. Though meteorological factors may have an impact on triggering new episodes in bipolar patients, they do not constitute a dominant cause.

Clinical and psychometric validation of the psychotic depression assessment scale

BACKGROUND Recent studies have indicated that the 11-item Psychotic Depression Assessment Scale (PDAS), consisting of the 6-item melancholia subscale (HAM-D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a valid measure for the severity of psychotic depression. The aim of this study was to subject the PDAS, and its depression (HAM-D6) and psychosis (BPRS5) subscales to further validation. METHODS Patients diagnosed with psychotic depression at Danish psychiatric hospitals participated in semi-structured interviews. Video recordings of these interviews were assessed by two experienced psychiatrists (global severity rating of psychotic depression, depressive symptoms and psychotic symptoms) and by two young physicians (rating on 27 symptom items, including the 11 PDAS items). The clinical validity and responsiveness of the PDAS and its subscales was investigated by Spearman correlation analysis of the global severity ratings and the PDAS, HAM-D6, and BPRS5 total scores. The unidimensionality of the scales was tested by item response theory analysis (Mokken). RESULTS Ratings from 39 participants with unipolar psychotic depression and nine participants with bipolar psychotic depression were included in the analysis. The Spearman correlation analysis indicated that the PDAS, HAM-D6 and BPRS5 were clinically valid (correlation coefficients from 0.78 to 0.85, p<0.001) and responsive (correlation coefficients from 0.72 to 0.86, p<0.001) measures of psychotic depression. According to the Mokken analysis, all three scales were unidimensional. CONCLUSIONS The clinical validity, responsiveness and unidimensionality of the PDAS and its subscales were confirmed in an independent sample of patients with psychotic depression.

The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine

OBJECTIVE To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). METHODS In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. RESULTS PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. LIMITATIONS The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. CONCLUSIONS It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients.

LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark

Abstract Background: New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s. Aims: The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients. Methods: The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material. Results: LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients. Conclusions: Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.

Fewer re-admissions and bed days following an intensive transitional post-discharge aftercare programme for a mixed diagnostic group of patients

Abstract Background: The organization of aftercare is important for a successful outcome; still the optimal organization has not been fully explored. An intensive transitional post-discharge aftercare (TA) programme, for a mixed group of non-psychotic patients, was recently developed. Patients with non-psychotic diagnoses are often discharged with low well-being while still symptomatic, placing high demands on aftercare. Aims: To evaluate retrospectively the short and long-term mental healthcare service use during and after the TA programme compared with the service use of a retrospective comparison group (RC), receiving less intensive outpatient aftercare. Methods: Number of re-admissions, bed days and emergency visits after 10 weeks, 6 months and 1 year was retrospectively collected from electronic patient registers. Descriptive statistics, independent samples T-tests and repeated-measures analysis of variance was used to compare the groups. Results: The majority of patients in both groups suffered from affective disorders, followed by personality disorders and a small number of other psychiatric diagnoses. Service use in the TA group was lower than in the RC group with fewer bed days after 10 weeks (P = 0.01) and after 6 months (P = 0.003), and fewer re-admissions after 6–12 months (P = 0.04). Emergency contacts did not differ significantly between the two groups at any point. Conclusions: The present study indicates beneficial effects of intensive TA, for a mixed group of non-psychotic patients. The lower service use in the TA programme group is in line with day treatment programme research for patients with affective disorders.

Danish translation and validation of Kessler’s 10-item psychological distress scale – K10

Abstract Background: Psychological distress is a trans-diagnostic feature of mental suffering closely associated with mental disorders. Kessler’s 10-item Psychological Distress Scale (K10), a scale with sound psychometric properties, is widely used in epidemiological studies. Aim: To translate and investigate whether K10 is a reliable and valid rating scale for the measurement of psychological distress in a Danish population. Methods: The translation was carried out according to official WHO translation guidelines. A sample of 100 subjects was included, 54 patients from the regional Mental Health Service (MHS) and 46 subjects with no psychiatric history. All participants were assessed with a psychiatric diagnostic interview (MINI) and handed out K10. Concurrent validity was assessed by WHO Well-being Index (WHO-5). Correlation matrix analysis was conducted for the full sample and receiver operating characteristic (ROC) curves for discriminating mental health service affiliation. Results: Mean K10 scores differed, with decreasing levels, between inpatients and outpatient in MHS and the subjects with no psychiatric history. Factor analysis confirmed a unidimensional structure, and Cronbach’s alpha and Omega showed excellent internal reliability. AUC for the K10 ROC curves showed excellent sensitivity (0.947 [0.900–0.995]), accurately differentiating mental health from non-mental health patients. Conclusion: The Danish K10 has the same strong internal reliability as the original English version, and scores differ between psychiatric patients in outpatient and emergency ward settings. Clinical implications: The Danish K10 translation is authorized and freely available for download at https://www.hcp.med.harvard.edu/ncs/k6_scales.php. The utility as an instrument for clinical screening in a mental healthcare setting is supported.