Relationship between neuroticism personality trait and serotonin transporter binding.

BACKGROUND: Personality trait is thought to be one of the important factors for vulnerability to depression. The relation between serotonin transporter (5-HTT) polymorphism and anxiety-related personality has been investigated in genetic research. In this study, we investigated the relation between in vivo regional 5-HTT binding in the brain and personality inventory measures in normal male volunteers. METHODS: Thirty-one healthy male volunteers underwent positron emission tomography scans with (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl) benzonitrile ([(11)C]DASB) to measure 5-HTT and completed revised NEO Personality Inventory. Correlation of [(11)C]DASB binding potentials (BP) with personality inventory measures was calculated using region-of-interest analysis and statistical parametric mapping based on the BP images. RESULTS: Neuroticism was positively correlated with 5-HTT binding in the thalamus (p = .004). No significant correlation was observed in any other brain region. Within the neuroticism dimension, the facet of depression was positively correlated with 5-HTT binding in the thalamus (p = .001). CONCLUSIONS: Subjects with higher thalamic 5-HTT binding are more likely to express higher levels of neuroticism and depressive feeling. Serotonin transporter binding in the thalamus might be a marker of vulnerability to depression.     

Imipramine binding sites on platelets of patients with major depressive disorder

3H-Imipramine binding to platelets of patients with primary, unipolar major depressive disorder was investigated and compared to that of a normal, healthy control population. No significant differences could be demonstrated between either the Kd or the Bmax values of the two groups. A negative correlation was observed between imipramine Bmax values and the Hamilton anxiety ratings of the depressed patients. Patients who displayed psychomotor retardation tended to have lower platelet imipramine Bmax values than patients with psychomotor agitation. It is suggested that platelet imipramine Bmax values may be a biological marker for subtypes of depression.     

Biological markers in juvenile depression

3H-p-Aminoclonidine binding to platelets of children and adolescents with major depressive disorder was compared to that of a healthy control population. Significantly higher alpha 2-adrenoceptor Kd and Bmax values were observed in the patient population. 3H-Dihydroalprenolol binding to lymphocyte membranes of the same patient population showed significantly higher beta-adrenoceptor Bmax values than controls. Control females had significantly higher beta-adrenoceptor Kd values than control males, and the female patients had significantly lower beta-adrenoceptor Kd values than control females. 3H-Imipramine binding to platelets of these patients showed significantly higher imipramine Kd values in patients with a suicide attempt, whereas the imipramine Bmax values were significantly increased in patients with major depressive disorder with or without a suicide attempt. We propose that increased platelet alpha 2-adrenoceptor Kd and Bmax values, together with increased platelet imipramine Kd values, may serve as possible biological markers for children and adolescents with major depressive disorder and a tendency toward suicide. Elevated platelet imipramine and lymphocyte beta-adrenoceptor Bmax values may be biological markers for juvenile depression, and decreased beta-adrenoceptor Kd values may be a biological marker for depression in young females.     

A study of platelet serotonin receptor in mania.

BACKGROUND: Serotonergic (5-HT) dysfunction has been hypothesized in mania; however platelet studies on the 5-HT uptake rate and the 5-HT transporter have revealed inconsistent results. To the best of our knowledge no studies have been conducted on the 5-HT2 receptor status in mania. METHODS: We determined density (Bmax) and dissociation constant (Kd) of 5-HT2 receptors in the platelets of 29 normal control and 29 manic subjects using 125I-ketanserin as the binding radioligand. The manic patients were assessed for the same after 14 days of treatment with lithium (n = 14) and after return to premorbid levels of functioning (n = 5). RESULTS: There were no significant differences in the Bmax (3.51 +/- 3.04 vs. 3.14 +/- 3.44 fmol/mg protein, p = ms) values between normal control and manic subjects. In comparison to the baseline values Bmax at day 14 (3.49 +/- 3.68 vs. 2.18 +/- 1.90 fmol/mg protein, p = ns) and following recovery (1.17 +/- 0.85 vs. 1.29 +/- 1.13 fmol/mg protein, p = ns) did not show any significant difference. CONCLUSIONS: Our findings preliminarily suggest that the platelet 5-HT2 receptor is neither a state marker nor a trait marker in mania; however studies on the 5-HT2 receptor using positron-emission tomography ligands will help in conclusively ruling out the involvement of this receptor in mania.     

Serotonin transporter availability in impulsive aggressive personality disordered patients: A PET study with [11C]DASB

Serotonin (5-HT) has consistently been implicated in the pathophysiology of impulsive aggression. In the current study, we tested the hypothesis that 5-HT transporter (5-HTT) binding is reduced in the anterior cingulate cortex (ACC) in impulsive aggressive patients. Additionally, we characterized pathological personality dimensions, with a specific focus on callousness (i.e. emotional indifference, a facet of psychopathy). Callousness is putatively positively correlated with presynaptic 5-HT, and thus could potentially confound the hypothesized negative relation between 5-HTT levels and trait aggression.We determined 5-HTT binding with positron emission tomography and [¹¹C]DASB in 29 patients with intermittent explosive disorder (IED-IR) and 30 controls. We assessed group differences in 5-HTT binding in the pregenual ACC, amygdala and subcortical regions and examined correlations between 5-HTT binding and clinical measures.There were no significant differences in 5-HTT binding between IED-IR patients and controls. Trait callousness exhibited a significant, positive correlation with ACC 5-HTT availability. Among IED-IR patients, a trend-level negative partial correlation was observed between trait aggression and ACC 5-HTT availability, while covarying for callousness and age. Exploratory analyses revealed a significant negative correlation between state aggression levels and 5-HTT availability in subcortical regions, namely striatum and thalamus.We did not confirm our hypothesis of lower ACC 5-HTT availability in impulsive aggressive patients, however, the positive correlation between callousness and ACC 5-HTT availability likely played a confounding role. Subtypes of aggression (e.g., reactive vs. proactive aggression), which are differentially associated with pathological personality dimensions such as callousness, may contribute to variability between 5-HT functioning and aggression.     

Rat strain differences in peripheral and central serotonin transporter protein expression and function

Female Fischer 344 (F344) rats have been shown to display increased serotonin transporter (5-HTT) gene expression in the dorsal raphe, compared to female Lewis (LEW) rats. Herein, we explored, by means of synaptosomal preparations and in vivo microdialysis, whether central, but also peripheral, 5-HTT protein expression/function differ between strains. Midbrain and hippocampal [3H]paroxetine binding at the 5-HTT and hippocampal [3H]serotonin (5-HT) reuptake were increased in male and female F344 rats, compared to their LEW counterparts, these strain differences being observed both in rats of commercial origin and in homebred rats. Moreover, in homebred rats, it was found that these strain differences extended to blood platelet 5-HTT protein expression and function. Saturation studies of midbrain and hippocampal [3H]paroxetine binding at the 5-HTT, and hippocampal and blood platelet [3H]5-HT reuptake, also revealed significant strain differences in Bmax and Vmax values. Although F344 and LEW rats differ in the activity of the hypothalamo-pituitary-adrenal (HPA) axis, manipulations of that axis revealed that the strain differences in hippocampal [3H]paroxetine binding at 5-HTTs and [3H]5-HT reuptake were not accounted for by corticosteroids. Hippocampal extracellular 5-HT levels were reduced in F344 rats, compared to LEW rats, with the relative, but not the absolute, increase in extracellular 5-HT elicited by the local administration of citalopram being larger in F344 rats. Because the aforementioned strain differences did not lie in the coding sequences of the 5-HTT gene, our results open the promising hypothesis that F344 and LEW strains model functional polymorphisms in the promoter region of the human 5-HTT gene.     

Serotonin uptake by blood platelets of schizophrenic patients

Active uptake of serotonin (5-hydroxytryptamine, 5-HT) by blood platelets of acute and chronic schizophrenic patients was compared with that of normal controls. Unlike previous reports, no significant difference in the kinetic parameters (Km and Vmax) of 5-HT uptake between schizophrenic patients and normal controls was observed, although a trend toward decreased Vmax in the acute schizophrenics was present. Since decreased Vmax of platelet 5-HT uptake has been found in patients with bipolar, unipolar, and schizoaffective depression, further study of the usefulness of platelet 5-HT uptake as a biological marker for major depressive illness is indicated. Abnormalities of 5-HT uptake do not appear to contribute significantly to the increased platelet 5-HT levels which have been reported in schizophrenic patients.     

Lack of association between suicidal ideation and enhanced platelet 5-HT2A receptor-mediated calcium mobilization in cancer patients with depression.

BACKGROUND: Increased density of 5-HT2A receptors was observed in the platelets of depressive patients with suicidal ideation. Enhanced 5-HT2A receptor-mediated platelet calcium mobilization has been proposed as a biological marker for the pathophysiology of major depression in cancer patients as well as in physically healthy patients. To examine whether depressive cancer patients with suicidal ideation have enhanced 5-HT2A receptor-mediated platelet response compared with those without suicidal ideation, we compared 5-HT-induced platelet calcium mobilization in depressive cancer patients with and without suicidal ideation. METHODS: 5-HT-induced platelet calcium mobilization was examined in 24 cancer patients diagnosed as having major depression according to the DSM-IV criteria. Suicidal ideation was evaluated by the Hamilton Depression Rating Scale and Zung's Self Depression Scale, as well as by the DSM-IV criteria. RESULTS: There was no significant differences in 5-HT-induced platelet calcium response between the depressive cancer patients with (n = 8) and without suicidal ideation (n = 16). 5-HT-induced platelet calcium response was also not significantly associated with the severity of suicidal ideation or with the severity of depression assessed by Hamilton Depression Rating Scale and Zung's Self Depression Scale. CONCLUSIONS: These findings suggest that enhanced 5-HT2A receptor-mediated response was not associated with suicidal ideation in cancer patients with depression.     

Platelet [3H]imipramine binding in affective disorders: trait versus state characteristics

Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders.     

Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology.

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-na?ve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-na?ve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-na?ve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-na?ve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments.     

Genetics of the serotonergic system in suicidal behavior

Genetic factors contribute to the risk of psychopathology in many psychiatric conditions, but the specific genes are yet to be identified. Neurotransmitter alterations are implicated in the etiology of psychopathology based, in part, on studies of neurotransmitter receptors and their biosynthetic or degradative enzymes in postmortem tissue. Identification of the altered receptors and enzymes serves to identify candidate genes of potential etiological significance. Polymorphisms in these genes can contribute to alterations in protein function in vivo that are part of the neurochemical underpinnings of psychopathologies such as major depressive disorder, psychoses, alcoholism, personality disorders, aggressive-impulsive traits, or suicidal behavior. Altered serotonergic function is implicated in the etiology and pathogenesis of several major psychiatric conditions. In particular, there is much evidence for an association of lower serotonergic function and suicidal behavior. Thus genes related to the serotonergic system are candidate genes worthy of study as part of the genetic diathesis for suicidal behavior. This review examines the following polymorphisms in the serotonin biosynthetic enzyme tryptophan hydroxylase (TPH; A779C substitution), the serotonin transporter (5-HTT, 5-HTTLPR allele), the 5-HT(1B) receptor (G861C, C129T substitution) and the 5-HT(2A) receptor (T102C) for their relationship to suicidal behavior. For the TPH gene, we found the less common U or A allele variant of the A779C polymorphism was associated with suicide attempt. Other studies have found the U allele to be associated with aggression and lower serotonergic function in vivo. A 44 base pair insertion/deletion in the 5' flanking promoter region of the 5-HTT gene may result in less 5-HTT expression and 5-HTT binding. We examined 220 cases postmortem and found no association between the promoter genotype and 5-HTT binding. We also found no association with major depressive disorder (MDD), suicide or pathological aggression, despite finding significantly fewer 5-HTT sites in the prefrontal cortex of depressed and/or suicide cases. In genomic DNA samples from 178 unrelated subjects, we detected two polymorphisms for the 5-HT(1B) receptor at nucleotides 861 and 129. However, no association between either polymorphism and depression, suicide, aggression, or alcoholism was observed. There are two common polymorphisms for the 5-HT(2A) receptor gene in humans. The results of studies of 5-HT(2A) receptor gene polymorphisms do not indicate significant major associations with suicidal behavior. In contrast, the 5-HT(2A) receptor itself is reported to be increased in suicide. Functional polymorphisms involving the promoter region that affect gene expression may explain this finding. Studies of candidate genes related to serotonergic function in brain are increasingly used to establish genetic alterations contributing to psychiatric illness. The most meaningful studies combine the study of candidate genes with direct measures of related proteins as well as psychopathology.     

Can serotonin transporter genotype predict serotonergic function,chronicity, and severity of drinking?

Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5'-HTTLPR) among healthy control subjects but not alcohol-dependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5'-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p<0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of Bmax for paroxetine binding, but not Vmax for serotonin (5-HT) uptake, was lower than that for SS subjects (p<0.05). More L-carriers than their SS counterparts had Vmax for 5-HT uptake below 200 nmol/10(7) platelets-min (p<0.05) and Bmax for paroxetine binding below 600 nmol/mg protein (p<0.06). Current drinking (drinks per day during the past 14 days) correlated positively with Km and Vmax of platelet 5-HT uptake (p<0.05) and negatively with Bmax, but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with Km and Vmax of platelet 5-HT uptake (p<0.05) and B(max), but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.     

Cytokines and serotonin transporter in patients with major depression

Altered cytokine secretion as a mechanism in the etiology of depression is still obscure. The serotonin transporter (5-HTT) may play an important role in the termination of serotonergic neurotransmission by serotonin (5-HT) uptaking into presynaptic neurons and representing as an initial action site for selective 5-HTT reuptake inhibitors (SSRI). In our study, we evaluated whether cytokines and 5-HTT acted as biological markers for depression. Blood samples were collected from 42 participants. The differences in cytokine and 5-HTT mRNA expressions of leukocytes were assessed between the patients with major depression (n=20) and the healthy controls (n=22), along with the measurements prior and after treatment with a SSRI, fluoxetine, for 3 months in the follow-up patient group (n=8). The results revealed that the mRNA expressions of IL-1beta, IL-6, IFNgamma, TNFalpha, and 5-HTT were higher in the depressed patients than those of the healthy controls. The higher level of mRNA expressions of IFNgamma and 5-HTT diminished after fluoxetine treatment. Furthermore, we found a positive correlation between 5-HTT and cytokines mRNA expressions in total participants, which suggested that pro-inflammatory cytokines and 5-HTT might play critical roles in the pathogenesis of major depression and that their levels were affected by chronic treatment with 5-HTT inhibitors.     

Tyramine-conjugation deficit as a trait-marker in endogenous depressive illness

Patients with endogenous unipolar depressive illness show a highly significant decrease in ability to metabolize an oral load of tyramine to its sulphate conjugatecompared with controls and neurotic depressives. As this biochemical lesion persists after clinical recovery and is present in about half the non-depressed first degree relatives of endogenously depressed probands, it is likely that the abnormality is a trait marker for depressive illness. It may thus be useful in practice as a predictor of vulnerability to depressive illness. The tyramine test is superior to the dexamethasone suppression test in both sensitivity to, and specificity for, endogenous depression.     

Lack of seasonal variation in platelet [3H]imipramine binding in humans

The Bmax of [3H]imipramine (IMI) binding has been reported to be reduced in platelets of depressed untreated patients as compared with normal controls. However, it has also been suggested that this difference could be related to the failure to take into account seasonal variations in the binding parameters for [3H]IMI recognition sites in platelets. For this reason, [3H]IMI binding was studied throughout 1 year in platelet membranes from 11 control volunteers, with blood samples collected once a month. The Bmax and Kd values of [3H]IMI binding showed no significant variation throughout the 12-month period of the study. These results indicate that in the control population, the platelet [3H]IMI binding parameters remain stable, and that the decrease in Bmax observed in depressed untreated patients reflects a genuine difference, which may be considered to be a biological marker in depression.     

Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.

BACKGROUND: Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD. METHODS: The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34). RESULTS: Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects. CONCLUSIONS: The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.     

Platelet tritiated imipramine binding in psychiatric patients: relationship to symptoms and severity of depression

The clinical and research significance of reduced imipramine binding has remained unclear despite considerable investigation. This study used an assay of demonstrated reliability to investigate the clinical correlates of imipramine binding to platelets in 63 depressed and 33 nondepressed psychiatric patients and 40 healthy control subjects. Both patient groups had Bmax values significantly lower than those of the healthy controls. Unequivocal associations between binding parameters and individual symptoms or groups of symptoms were not established, but a negative correlation between Kd and the number of adverse life events experienced in the preceding 6 months was apparent. These findings provide no support for the view that reduced binding is a trait marker for susceptibility to depression and cast doubt on its specificity as a state marker for the syndrome of depression.     

Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients

BACKGROUND: recent investigations have suggested that the phosphoinositide (PI) signal transduction system may be involved in the pathophysiology of bipolar affective disorders. Earlier studies in our laboratory have implicated altered PKC-mediated phosphorylation in bipolar affective disorder and in the clinical action of lithium. In the present study, we compared PKC activity and its translocation in platelets from subjects with bipolar affective disorder and three other groups. METHODS: subjects included 44 with bipolar disorder (acute manic episode), 25 with acute major depression, 23 with schizophrenia in acute exacerbation and 43 controls free of personal or family history of an Axis I disorder. Blood platelet membrane and cytosol PKC activity was measured before and after in vitro stimulation with serotonin (5-HT), thrombin and the direct PKC activator, PMA. In addition, we examined 5-HT-, thrombin- and PMA-elicited translocations of PKC isozymes from cytosol to the membrane in platelets of control subjects. RESULTS: in the basal state, manic subjects demonstrated higher membrane PKC activity than depressive and control subjects. The ratio of membrane to cytosol PKC activity was significantly higher in manic (1.10), as compared to control (0.84), depressed (0.93) or schizophrenic (0.93) subjects. Stimulation of platelets with 5-HT in vitro, resulted in greater membrane to cytosol ratio in the manic subjects compared to the three other groups. The responsiveness of platelets to PMA and thrombin was greater for manic subjects than for depressed and schizophrenic subjects, but not greater than the controls. In this measure both the schizophrenic and depressive groups were less active than controls. The results also demonstrate that platelets contain alpha-, beta-, delta- and zeta-PKC isozymes. While alpha- and beta-PKC isoforms were translocated from cytosol to membrane in response to serotonin, PMA and thrombin, serotonin also elicited the redistribution of delta-PKC and thrombin also activated zeta-PKC. CONCLUSION: the results demonstrate that a heightened PKC-mediated signal transduction is associated with acute mania and suggest a decreased transduction in patients with unipolar depression or schizophrenia.     

Decreased plasma serotonin in melancholic patients: a study with clomipramine

Eighteen unmedicated patients suffering from major depressive disorder with melancholia (DSM-III) were examined for abnormalities in peripheral serotonin (5-HT) and related metabolites. Serotonin in platelet-free plasma and in platelets from melancholics was significantly reduced to 30% and 60% of their respective control values. Plasma 5-hydroxyindoleacetic acid was also found to be reduced, but not significantly. Other plasma compounds related to 5-HT (indoleacetic acid, total tryptophan, and free tryptophan) were found to be unchanged in these patients. Of all variables, only platelet 5-HT was affected while patients were on clomipramine (CIM) treatment. After 2 weeks on CIM (100-150 mg/day, orally), platelet 5-HT was reduced to 8% of pretreatment values, but plasma 5-HT did not change and continued to be reduced upon clinical recovery. The existence of a distinct pool of plasma 5-HT that is clearly independent of the platelet pool is indicated by the differences observed in plasma and platelet 5-HT during CIM treatment, as well as by previous data from this laboratory. The very marked decrease in plasma 5-HT levels may be in accord with the central nervous system changes reported in depression and suggests the possibility of using plasma 5-HT as a peripheral indicator of abnormal serotonin function in melancholia.     

Platelet [3H]imipramine binding in psychiatric disorders

The Bmax and Kd values for [3H]imipramine binding were measured in platelets from drug-free normal controls and schizophrenic and depressive patients. No differences among groups were found. Exacerbated and remitted patients with either schizophrenia or depression did not differ in platelet [3H]imipramine binding parameters. No correlations were observed between platelet [3H]imipramine binding parameters and measures of symptom severity among actively ill patients with either schizophrenia or depression.