Tom G. Bolwig

Increased neurogenesis in a model of electroconvulsive therapy

BACKGROUND Electroconvulsive therapy (ECT) is a widely used and efficient treatment modality in psychiatry, although the basis for its therapeutic effect is still unknown. Past research has shown seizure activity to be a regulator of neurogenesis in the adult brain. This study examines the effect of a single and multiple electroconvulsive seizures on neurogenesis in the rat dentate gyrus. METHODS Rats were given either a single or a series of 10 electroconvulsive seizures. At different times after the seizures, a marker of proliferating cells, Bromodeoxyuridine (BrdU), was administered to the animals. Subsequently, newborn cells positive for BrdU were counted in the dentate gyrus. Double staining with a neuron-specific marker indicated that the newborn cells displayed a neuronal phenotype. RESULTS A single electroconvulsive seizure significantly increased the number of new born cells in the dentate gyrus. These cells survived for at least 3 months. A series of seizures further increased neurogenesis, indicating a dose-dependent mechanism. CONCLUSIONS We propose that generation of new neurons in the hippocampus may be an important neurobiologic element underlying the clinical effects of electroconvulsive seizures.

The Bech-Rafaelsen Mania Scale and the Hamilton Depression Scale

In a study of 18 patients with manic symptomatology and 31 patients with melancholic symptomatology the Bech‐Rafaelsen Mania Scale (BRMS) and the Hamilton Depression Scale (HDS) have been compared. The results showed that the inter‐observer reliability of the BRMS was adequate compared with the HDS. Both scales are constructed for assessing the severity of manic or melancholic states, and no difference was found in the total BRMS or HDS score between the various diagnostic groups, when the patients were classified by an index of the course and symptomatology of their disorder, using the Multi‐axial Classification System for Affective Disorders (MULTI‐CLAD). The homogeneity of the BRMS seemed more adequate than that of the HDS, when each item was correlated to the corresponding total score. Although the homogeneity of the BRMS needs to be evaluated by other statistical models than correlation analysis, our results seem to indicate that the improvement in assessing manic‐melancholic states quantitatively is a matter of redefining items or incorporating new items in the melancholic rather than the manic part of these rating scales.

Increased risk of developing Parkinson's disease for patients with major affective disorder: a register study

Objective:  To investigate whether patients with a diagnosis of affective disorder are at an increased risk of developing Parkinsons disease compared with medically ill control groups.

The permeability of the blood—brain barrier during electrically induced seizures in man

Abstract. The blood‐brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone [8]. Using 113mIn‐DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl‐, 14C‐urea and 14C‐thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra‐arterial 133Xe‐injection method. Twenty‐two patients receiving electro‐convulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl‐ 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability‐surface area products (PS) in ml/100 gX min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly.

Issues for DSM-5: Whither Melancholia? The Case for Its Classification as a Distinct Mood Disorder

Melancholia, a syndrome with a long history and distinctly specific psychopathological features, is inadequately differentiated from major depression by the DSM-IV specifier. It is neglected in clinical assessment (e.g., in STAR*D [1]) and treatment selection (e.g., in the Texas Medication Algorithm Project [2]). Nevertheless, it possesses a distinctive biological homogeneity in clinical experience and laboratory test markers, and it is differentially responsive to specific treatment interventions. It therefore deserves recognition as a separate identifiable mood disorder. Melancholia has been variously described as “endogenous,” “endogenomorphic,” “autonomous,” “type A,” “psychotic,” and “typical” depression (3–6). In contrast to the current DSM criteria for the melancholia specifier (features of which are often shared with major depression), it has characteristic clinical features (5–7).

The influence of climate on development of winter depression

126 patients suffering from winter depression participated in the study. Every second week patients completed the 13 item Beck Depression Inventory (BDI) in the period September to May in the years 1991 to 1994. Local weather data from this period were obtained from the Meteorological Institute, Copenhagen. No significant correlation was found between score on BDI and cloud cover, rainfall or atmospheric pressure. A significant correlation was found between score on BDI and minutes of sunshine, global radiation, length of daylight and temperature. This is in accordance with the theory, that lack of light is a contributing factor for development of winter depression.

Major depressive disorder in Parkinson's disease: a register-based study.

Nilsson FM, Kessing LV, Sørensen TM, Andersen PK, Bolwig TG. Major depressive disorder in Parkinsons disease: a register‐based study. Acta Psychiatr Scand 2002: 106: 202–211.

Role for M5 muscarinic acetylcholine receptors in cocaine addiction.

Muscarinic cholinergic receptors of the M5 subtype are expressed by dopamine‐containing neurons of the ventral tegmentum. These M5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M5 receptors in the reinforcing effects of cocaine was investigated using M5 receptor‐deficient mice in a model of acute cocaine self‐administration. The M5‐deficient mice self‐administered cocaine at a significantly lower rate than wild‐type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M5‐deficient mice spent significantly less time in the cocaine‐paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal‐associated anxiety measured in the elevated plus‐maze) was significantly attenuated in mice lacking the M5 receptor. These results demonstrate that M5 receptors play an important role in mediating both cocaine‐associated reinforcement and withdrawal.

Differential roles for neuropeptide Y Y1 and Y5 receptors in anxiety and sedation

Central administration of neuropeptide Y (NPY) causes both anxiolysis and sedation. Previous studies suggest that both effects are mediated via NPY Y1 receptors. However, most of these studies were carried out before the advent of specific NPY receptor ligands. Therefore, a potential role for other NPY receptors in anxiety and sedation remains a possibility. In the present study, we addressed this issue by testing the effects of intracerebroventricular (i.c.v.) injection of NPY as well as specific receptor agonists for the Y1 receptor ([D‐His26]NPY), Y2 receptor (C2‐NPY), and Y5 receptor ([cPP1–7,NPY19–23,Ala31,Aib32,Gln34]hPP) in the elevated plus maze and open field tests. As with NPY, the Y1 agonist had a dose‐dependent anxiolytic‐like effect in both behavioral tests. In contrast to NPY, which caused significant sedation in the open field test, the Y1 agonist was without sedative effect. The Y2 agonist showed neither anxiolytic‐like nor sedative effects. The Y5 agonist showed anxiolytic‐like activity in both behavioral tests and caused sedation in the same dose range as NPY in the open field test. These results indicate that anxiolytic‐like effects of i.c.v.‐administered NPY in rats are mediated via both Y1 and Y5 receptors, whereas sedation is mediated via Y5 receptors.

Electroconvulsive shocks increase the expression of neuropeptide Y (NPY) mRNA in the piriform cortex and the dentate gyrus

Repeated electroconvulsive stimulations represent one treatment modality for depressive disorders, but the mechanism leading to its effect is largely unknown. Studies of humans and rats have indicated that neuropeptide Y (NPY) is involved in major depression and anxiety. The purpose of the present investigation was to detect changes in the expression of preproNPY mRNA in the limbic cortex of rats exposed to electroconvulsive shocks (ECS) daily for 14 days. Twenty-four hours after the last ECS, the animals were sacrificed, brain sections were hybridized with a synthetic oligonucleotide probe complimentary to rat preproNPY mRNA. Semi-quantitative in situ hybridization histochemistry revealed an about ten-fold increase of preproNPY mRNA levels over the dentate gyrus and the piriform cortex in animals exposed to ECS compared to sham-treated controls. In the dentate gyrus dipped sections showed that the increase of gene expression took place in individual neurons in the polymorph layer. In the piriform cortex a moderate increase in the number of grains was observed over many individual cells in the pyramidal layer. These data show that the expression of preproNPY mRNA is markedly increased in specific brains regions after ECS, but whether this increase is a result of the ECS-induced seizures per se, or rather should be regarded as a protective adaptation to changes in neuronal activity pattern remains to be established.