Björn Wahlund

Platelet serotonin functions in untreated major depression

The uptake of [14C]5-HT, [3H]paroxetine and [3H]LSD binding was determined in platelets from 30 untreated patients with major depression and compared with corresponding variables from 30 healthy age-, sex- and season-matched control subjects. The maximum velocity (Vmax) for the 5-HT uptake was significantly decreased in patients (P = 0.014) compared to control subjects. Depressed women had significantly lower Vmax than female control subjects. In men, Vmax did not differ between patients and control subjects. Vmax was significantly lower in male inpatients compared with male outpatients (P = 0.05). The density (Bmax) of 5-HT uptake sites was found to be significantly increased in patients (P < 0.05) compared to control subjects and male patients had significantly higher Bmax than male control subjects, but there was no difference between female control subjects and female patients. No significant difference was found in Bmax of 5-HT2-receptors between patients and control subjects. A positive correlation was found between Bmax of 5-HT2-uptake sites and the degree of anxiety and between Bmax of 5-HT2 receptors and MADRS scores. Bmax of 5-HT2-receptors was positively correlated with the degree of suicidality. The results in the present study indicate that there may be a gender difference in serotonergic dysfunction in depression.

Classification of patients with affective disorders using platelet monoamine oxidase activity, serum melatonin and post-dexamethasone cortisol

Platelet monoamine oxidase activity (MAO), melatonin and Cortisol post‐dexamethasone suppression test (DST) were examined in 28 patients with major affective disorder and in 20 controls. MAO activity was lower and Cortisol post‐dexamethasone was higher in depressed patients. Platelet MAO activity and Cortisol in depressed and controls yielded high sensitivity (90%) and specificity (89%). The patients were re‐examined after 10 years and categorized into affective psychosis or neurotic depression (ICD‐9). Multidimensional analysis identified one subgroup coinciding in 92% with affective psychosis and another subgroup coinciding in 87% with neurotic depression. Combination of MAO, melatonin and post‐DST Cortisol may be useful in the diagnosis of subgroups of depressed patients and in choice of therapy.

Clinical symptoms and platelet monoamine oxidase in subgroups and different states of affective disorders

Platelet monoamine oxidase activity (MAO) and clinical symptoms were examined in 116 individuals, 32 acute depressed patients and 84 healthy controls. The enzyme activity was lower in depressed women than controls. MAO activity correlated positively with rated clinical state in depressed women but not in depressed men. Patients were reexamined after 10 years and categorized into affective psychosis (endogenous) or neurotic depression (International Statistical Classification of Diseases, Injuries and Causes of Death, 1987; ICD-9). Neurotic depressed occurred frequently in the low activity group. Endogenously depressed showed positive correlation between MAO activity and rated clinical state. The association between platelet MAO activity and clinical state is discussed.

Affective disorder subtyped by psychomotor symptoms, monoamine oxidase, melatonin and cortisol: identification of patients with latent bipolar disorder.

Abstract A multivariate approach using pattern recognition method was applied on a multivariable data set from patients with affective disorders comprising biological and clinical variables. The depressed patients were rated according to 23 items of the comprehensive psychopathological rating scale (CPRS). Variables of importance were selected and clusters of patients were found by combining monoamine oxidase, melatonin and post-dexamethasone cortisol with symptoms of psychomotor retardation and agitation. Patients were distributed with high scores of agitation in the extreme of one direction and with high scores of retardation in the opposite direction. By using the combined clinical and biological variables, a diagnostic subcategory with latent bipolar disorder was identified. Two clusters of unipolar patients, one with low melatonin and low psychomotor retardation scores, and one with high melatonin and high psychomotor retardation scores, were found. Identification of a patient group with latent bipolar disorder may have potential therapeutic value since bipolar patients should be taken care of by a specialist in psychiatry, avoid tricyclic antidepressant therapy and may be candidates for lithium treatment.

Release of corticotropin after administration of corticotropin-releasing hormone in depressed patients in relation to the dexamethasone suppression test.

The possible hypersecretion involvement of corticotropin‐releasing hormone (CRH) in the pathophysiology of hypothalamic‐pituitary‐adrenocortical axis disturbances in patients with major depressive episode and with an abnormal dexamethasone suppression test (DST) was investigated. The corticotropin (ACTH) and cortisol response to the injection of 45 μg of synthetic human CRH at 1630 were analyzed in 24 inpatients with normal (suppressors) or abnormal (nonsuppressors) DST. The outcome of the DST was analyzed using 3 cut‐off points for the cortisol levels. The clinical assessments included two rating scales. The results showed that nonsuppressors had a significantly lower ACTH response to CRH stimulation than suppressors at all cut‐off points (calculated as net area under the curve and as the difference between the peak and the baseline level) despite no significant differences in the severity of depression.

A cortical network model for clinical EEG data analysis

Abstract We use computational models of neo-cortex to investigate how cortical neurodynamics may depend on network properties and on intrinsic and external signals and fluctuations. We have previously demonstrated plausible relations between structure, dynamics and function of a neural network model of paleo-cortex, and now use a similar paradigm for the neo-cortical case. We investigate the role of various network properties and external input on electroencephalography (EEG) dynamics, in particular relating to electroconvulsive therapy (ECT) of patients with major depression. Our results are suggestive for the neural mechanisms underlying EEG, as well as for the dynamical effects of ECT on human EEG.

Analysis of phase shifts in clinical EEG evoked by ECT

We propose a new strategy for studying the phase shifts of electroencephalography (EEG) after electroconvulsive therapy (ECT) of patients with major depression. We divide each ECT EEG time series into four phases and calculate the power spectrum and coherence of left and right prefrontal EEGs for each phase. Previously, we have qualitatively demonstrated certain ECT EEG dynamical patterns by using a neo-cortical neural network model. Now we quantitatively analyze the dynamical phase shifts of the ECT EEG data. Our results are suggestive for a deeper understanding of the ECT EEG patterns and for building more realistic cortical models.

Melatonin in Psychiatric Disorders – Subtyping Affective Disorder

Altered diurnal secretory patterns, i.e. altered phase and/or amplitude of melatonin have been reported in sleep and affective disorders. The alteration may depend on environmental factors which in vulnerable individuals may cause sleep and/or affective disorders. Early stress in conjunction with development of resistance to corticotropin-releasing hormone may be linked to the low melatonin syndrome in subgroups of depressed patients. Also the seasonal variation in melatonin as well as serotonin may be linked to the seasonal pattern seen in subgroups of affective disorders. Melatonin may be used as a combined marker for proneness to develop affective disorders especially in latent carriers of bipolar disorders.

Motor imagery in bipolar depression with slowed movement

Abstract We hypothesized that motor retardation in bipolar depression is mediated by disruption of the pre-executive stages of motor production. We used functional magnetic resonance imaging to investigate neural activity during motor imagery and motor execution to elucidate whether brain regions that mediate planning, preparation, and control of movement are activated differently in subjects with bipolar depression (n = 9) compared with healthy controls (n = 12). We found significant between-group differences. During motor imagery, the patients activated the posterior medial parietal cortex, the posterior cingulate cortex, the premotor cortex, the prefrontal cortex, and the frontal poles more than the controls did. Activation in the brain areas involved in motor selection, planning, and preparation was altered. In addition, limbic and prefrontal regions associated with self-reference and the default mode network were altered during motor imagery in bipolar depression with motor retardation.

Diagnostic subgrouping of depressed patients by principal component analysis and visualized pattern recognition

A data-analytical method is described for identifying behavioral and biological variables in psychiatric patients with predictive value in defining clinical subgroups. The procedure, based on principal component analysis (PCA) and graphical analysis, was applied in a group of 28 depressed patients. The 28 depressed patients of unipolar type were observed for up to 15 years for re-evaluation of the diagnoses at the start of the study. Platelet monoamine oxidase activity, post-dexamethasone serum cortisol and serum melatonin predicted two main clinical subgroups as well as a smaller subgroup of bipolar patients. The selection procedure revealed which of several variables were predictive of subgroups that were not possible to identify by univariate methods. The three biological variables may thus be useful in further assessment of clinical subgroups of unipolar depressed patients studied by other research groups.