Ramesh C. Arora

Increased serotonin2 (5-HT2) receptor binding as measured by 3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients

3H-Lysergic acid diethylamide (3H-LSD) binding, a putative measure of 5-HT2 receptor binding, was studied in the blood platelets of 29 depressed patients and 24 normal controls. The Bmax (maximum number of 3H-LSD binding sites) in the blood platelets of depressed patients was significantly greater than that of normal volunteers. This increase in Bmax was due to an increase in female depressed patients only. Bmax was significantly lower in female compared to male normal controls but there was no difference between male and female depressed patients. There was also no difference in Kd (an inverse measure of affinity of 3H-LSD binding to its sites) between normal controls and depressed patients. The correlations between Bmax of 3H-LSD binding and the Bmax of the 3H-imipramine binding site or the Vmax of 5-HT uptake sites were not significant. The role of serotonergic processes in the psychobiology of depression is discussed.

Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

Serotonin2 (5-HT2) receptor binding was studied, using3H-spiperone as the ligand, in post-mortem brain specimens obtained from schizophrenic patients (N=11) and non-psychiatric controls (N=11). The maximum number of binding sites (Bmax) was significantly decreased in schizophrenic patients as compared to normal controls. This difference did not appear to be due to neuroleptic treatment. No difference in Kd (an inverse measure of the affinity of3H-spiperone to its binding sites) was observed between the two groups. However, studies with unmedicated schizophrenic patients are needed to draw any definite conclusion. The role of serotonergic processes in the psychobiology of schizophrenia is discussed.

Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims

The density of 5-HT1A binding using3H-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (Bmax) or Kd (an inverse measure of affinity) of 5-HT1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher Bmax (22—25%) compared to both controls and violent suicides. A negative correlation between age and Bmax of 5-HT1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60.

Genetic control of serotonin uptake in blood platelets: A twin study

Platelet serotonin (5HT) uptake was studied in 13 pairs of monozygotic (MZ) twins, 13 pairs of dizygotic (DZ) twins, and 14 pairs of unrelated normal volunteers. Significant intraclass correlations (ICC) in the affinity (Km) of 5HT uptake in the blood platelets of MZ and DZ twins and unrelated pairs were found. However, the ICC for maximum velocity (Vmax) was significant only in MZ and DZ twins. The ICC of the Vmax of 5HT uptake of MZ twins was significantly greater than that of DZ twins and unrelated pairs. This suggests that the Vmax of 5HT uptake in blood platelets is, in part, heritable. Thus, low platelet 5HT uptake (Vmax) in major depression and other disorders may be genetically determined.

3H-imipramine binding in the frontal cortex of suicides

Imipramine binding (desipramine- and serotonin-sensitive) was determined in the frontal cortex of suicide victims and nonpsychiatric controls who died due to medical disease or accidents. There were no differences in Kd or Bmax of imipramine binding between controls and suicides. The Kd and Bmax values of serotonin-sensitive imipramine binding were significantly lower than desipramine-sensitive imipramine binding, both in controls and suicides. There were significant correlations between Kd and Bmax of serotonin-sensitive imipramine binding and desipramine-sensitive imipramine binding in suicides but not in controls.

Platelet markers of suicidality.

Six serotonergic measures in blood platelets, Km and Vmax of serotonin (5-HT) uptake, Kd and Bmax of 3H-imipramine binding, 5-HT content, and MAO activity, were measured in depressed and other psychiatric patients and related to Hamilton Depression Scale suicide ratings. Km was negatively correlated with the suicide rating while Kd was positively correlated with it. Multivariate analyses showed that Km, Kd, Vmax, and MAO activity were significant predictors of Hamilton Depression Scale suicide ratings. Low platelet MAO activity was present in seven nondepressed females who had made suicide attempts in the current episode. The direction of the association between the platelet measures and suicide ratings indicated diminished presynaptic serotonergic activity in patients with high suicide ratings, if the platelet findings could be extrapolated to 5-HT nerve terminals.

Serotonin Uptake and Imipramine Binding in the Blood Platelets of Obsessive-Compulsive Disorder Patients

14C-Serotonin (5-HT) uptake and 3H-imipramine binding (IB) were studied in the blood platelets of 20 obsessive-compulsive disorder (OCD) patients, 53 normal controls (5-HT uptake) and 32 normal controls (IB binding). The maximum number of binding sites (Bmax) was significantly decreased in OCD patients compared to normal controls, but there was no difference in the affinity for 3H-imipramine (Kd). The affinity for 5-HT uptake (Km) was also decreased in the OCD patients but the maximum velocity of 5-HT uptake sites (Vmax) was not significantly different in OCD patients and normal volunteers. There were trends for the Slowness Subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI) to be positively correlated with the Km of 5-HT uptake (p = 0.094), whereas the Global Scale, Checking Subscale, and Doubting Conscientiousness Subscale of MOCI were negatively correlated with the Kd of IB (p = 0.066, p = 0.08, and p = 0.062, respectively). The results provide further evidence for the dysfunction of the serotonergic system in OCD.

Laterality and 3H-imipramine binding: Studies in the frontal cortex of normal controls and suicide victims

Serotonin [5-hydroxytryptamine (5-HT)]-sensitive imipramine binding (IB) was determined in the left and right hemisphere of frontal cortex of suicide victims and nonpsychiatric controls who died due to myocardial infarction or accident. The Kd (an inverse measure of affinity of 3H-imipramine to its binding sites) was significantly higher in left hemisphere than right hemisphere in normal controls. There were no differences in Bmax and Kd or Bmax between left hemisphere and right hemisphere in normals and suicides, respectively. These results do not support the finding of hemispheric asymmetry of 5-HT uptake as measured by IB (Bmax) in postmortem tissue from controls and suicide victims.

Serotonergic measures in suicide brain: The concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and tryptophan (TRP) were determined in the frontal cortex of individuals who died by suicide, homicide, accident, or the result of physical diseases. Females had significantly higher tryptophan concentrations than males. There was a significant correlation HVA and the interval between death to refrigeration of the body. Mean HVA levels were higher from noon to 5 PM. Suicide and homicide victims had significantly higher cortical HVA concentrations than those who died of physical disease but not accident victims. This was not accounted for by gender, age, postmortem interval from death to refrigeration of the body or to autopsy, specimen storage time, or drug effects. The ratio of HVA/5-HIAA was also significantly higher in suicides compared with those who died of physical disease. No differences in cortical 5-HIAA or tryptophan concentrations between the four groups were found. There were no differences in the levels of the three substances in violent and nonviolent suicides. There were no significant correlations between 5-HIAA, HVA and TRP concentrations in all subjects or any of the four subgroups. The implications of these findings for the role of serotonin and dopamine in suicide and violence are discussed.

Effect of desipramine treatment on 3H-imipramine binding in the blood platelets of depressed patients

Platelet imipramine binding (IB) was studied in depressed patients before and after treatment with desipramine for 17-28 days. Administration of desipramine was associated with a significant increase in Bmax. There was a trend for an increase in Kd, but it did not reach statistical significance. The net result of the changes in Bmax and Kd was an increase in IB. There were significant correlations between the change in depression ratings and pretreatment Kd, as well as the change in Kd during treatment. These results suggest that decreased IB is not a trait-dependent marker, but a state-dependent marker for depression.