Cerebrospinal fluid monoamine and monoamine metabolite concentrations in melancholia

Roy, Alec; Pickar, David; Linnoila, Markku; Doran, Allen R.; Ninan, Philip T.; Paul, Steven M.

doi:10.1016/0165-1781(85)90065-4

Cited by 113 publications

(44 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lower dopamine concentrations were measured in CSF of depressed patients. 6 Dopamine transporter affinity measured with SPECT in the basal ganglia was higher in depressed patients than in healthy controls, indicating a diminished synaptic dopamine concentration. 7 Dopamine transporter (DAT1) activities were also found to be modulated by selective serotonin reuptake inhibitors (SSRIs), and extracellular striatal dopamine concentrations were reduced during medication with SSRIs.…”

Section: Introductionmentioning

confidence: 99%

A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment

et al. 2006

View full text Add to dashboard Cite

Finding predictors of the response to antidepressant therapy is a major goal of molecular psychiatry. The genes encoding the serotonin (SERT) and dopamine (DAT1) transporters are among the possible candidate genes modulating an individual's antidepressant response. In a naturalistic prospective cohort study with a total of 190 fully assessed patients, improvement of depression symptoms during the 3 weeks following initiation of antidepressant therapy was recorded using the 21-item Hamilton Depression Rating Scale (HDRS). The SLC6A3 3 0 UTR 40-bp variable number of tandem repeats (VNTR) and the SLC6A4 5 0 44-bp insertion/deletion polymorphism were analyzed by polymerase chain reaction. There was a significantly smaller number of rapid responders among homozygous carriers of the DAT1 9-repeat allele (9/9) than among heterozygous (9/10) and homozygous (10/10) carriers of the 10-repeat allele (19 versus 37 versus 52%, respectively, P ¼ 0.0037). Median decline in HDRS score was 35, 40, and 52% in patients with the 9/9, 9/10, and 10/10 genotypes, respectively (P ¼ 0.013). The effect was found in all classes of medications (selective serotonin reuptake inhibitors (SSRIs), tricyclics, mirtazapine, venlafaxine) and statistically significant also within the subgroup of patients having received SSRIs. The serotonin promoter insertion/deletion genotype had no effect in the entire study group, but there was an insignificant trend of better response in the l/l and l/s carriers who received SSRIs or mirtazapine. In conclusion, the dopamine transporter VNTR polymorphism influenced rapid response to antidepressant therapy. Compared with homozygous carriers of the 10-repeat allele, carriers of the 9/10 genotype had an odds ratio (OR) calculated by logistic regression analysis of 1.6 (95% CI 0.8-3.2) and carriers of the 9/9 genotype had an OR of 6.0 (1.5-24.4) for no or poor response. Further studies are required to confirm this clinical association and to elucidate the underlying mechanisms.

show abstract

Section: Introductionmentioning

confidence: 99%

A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The mesocorticolimbic DA system projects from the ventral tegmental area of the midbrain to the nucleus accumbens and plays a critical role in the control of reward and motivation, mechanisms which are disrupted in depression [17][18][19][20][21] . Previous studies have shown a reduced level of the DA metabolite homovanillic acid in the cerebrospinal fluid in depressed patients [22][23][24] . Furthermore, D2 or mixed D2/D3 receptor agonists exert antidepressant-like effects in diverse depression models [25,26] and appear to be effective in treatment-resistant depressed patients [27][28][29] .…”

Section: Introductionmentioning

confidence: 99%

Behavioral Actions of Intranasal Application of Dopamine: Effects on Forced Swimming, Elevated Plus-Maze and Open Field Parameters

et al. 2008

View full text Add to dashboard Cite

Background: Recently, we found evidence that intra-nasally administered dopamine (DA), can enter the brain, leading to an immediate increase in extracellular DA levels in striatal subregions. This offers a potential alternative approach to target the brain with exogenous DA, which otherwise cannot cross the blood-brain barrier. Here, we examined whether intra-nasally applied DA also exerts behavioral activity on mesocortical and nigrostriatal dopaminergic functions. Method: Male Wistar rats (3–4 months) were tested for potential behavioral effects of intra-nasally applied DA (0.03, 0.3 or 3.0 mg/kg) in the forced swimming test (FST) for antidepressant-like activity, elevated plus-maze for anxiety-related behavior, and on motor activity in a novel and familiar environment. Results: Intra-nasally administered dopamine in a dose of 0.3 mg/kg exerted antidepressant-like activity in the FST, but had neither anxiolytic-like nor anxiogenic-like effects in the elevated plus-maze. Furthermore, intra-nasal dopamine stimulated locomotor activity in a familiar, but not novel, open field. Conclusions: These results support the view that intra-nasally applied DA can act on the central nervous system by entering the brain via the nose-brain pathway, making this kind of application procedure a promising alternative for targeting the brain, and thus treating disorders involving mesocortical and/or nigrostriatal dopaminergic disturbances.

show abstract

“…See Table 1 for a summary (Malone and Mann 1993;Owens and Nemeroff 1994;Stoff and Mann 1997;Mann 1998). In major depression there are fewer platelet serotonin transporters (5-HTT), lower CSF 5-HIAA (Mendels et al 1972;Sjöström and Roos 1972;Ashcroft et al 1973aAshcroft et al , 1973bPost and Goodwin 1974;Bowers 1974;Goodwin and Post 1977;van Praag and de Haan 1979;Koslow et al 1983;Åsberg et al 1984;Gerner et al 1984;Roy et al 1985;Redmond et al 1986), as well as a reduced growth hormone (GH) response to 5-hydroxytryptophan (5-HTP) (Upadhyaya et al 1991) and a blunted prolactin (PRL) response to oral fenfluramine (Siever et al 1984;Coccaro et al 1989;O'Keane and Dinan 1991;Mann et al 1992) and to intravenous L-tryptophan (Heninger et al 1984;Cowen et al 1990;Price et al 1991;Upadhyaya et al 1991). The antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) suggests the abnormality in depression probably includes impaired serotonergic function, because selective enhancement of serotonergic activity is therapeutic (Åsberg et al 1986a).…”

mentioning

confidence: 99%

The Neurobiology and Genetics of Suicide and Attempted Suicide: A Focus on the Serotonergic System

Mann

2001

Neuropsychopharmacology

356

208

View full text Add to dashboard Cite

Neuro-receptors Major depression and suicidal behavior are independently related to altered serotonergic function (Mann and Stanley 1986). See Table 1 for a summary (Malone and Mann 1993;Owens and Nemeroff 1994;Stoff and Mann 1997;Mann 1998). In major depression there are fewer platelet serotonin transporters (5-HTT), lower CSF 5-HIAA (Mendels et al. 1972;Sjöström and Roos 1972; Ashcroft et al. 1973a Ashcroft et al. , 1973bPost and Goodwin 1974; Bowers 1974; Goodwin and Post 1977;van Praag and de Haan 1979;Koslow et al. 1983; Åsberg et al. 1984; Gerner et al. 1984;Roy et al. 1985;Redmond et al. 1986), as well as a reduced growth hormone (GH) response to 5-hydroxytryptophan (5-HTP) (Upadhyaya et al. 1991) and a blunted prolactin (PRL) response to oral fenfluramine (Siever et al. 1984; Coccaro et al. 1989;O'Keane and Dinan 1991;Mann et al. 1992) and to intravenous L-tryptophan (Heninger et al. 1984; Cowen et al. 1990;Price et al. 1991;Upadhyaya et al. 1991). The antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) suggests the abnormality in depression probably includes impaired serotonergic function, because selective enhancement of serotonergic activity is therapeutic (Åsberg et al. 1986a). Depletion of serotonin by parachlorophenylalanine (PCPA) (Shopsin et al. 1976) or by reduction of brain tryptophan (Delgado et al. 1990), quickly reverses the antidepressant effect of serotonergic medication in patients (Åsberg et al. 1986a), suggesting that sustained enhancement of serotonergic function is a necessary requirement to sustain this SSRI-mediated antidepressant effect. It seems that the abnormality in serotonergic function may be a biochemical trait, because a blunted prolactin response to fenfluramine and a vulnerability to depression in response to tryptophan depletion are present during the 24 , NO . 5 period of remission between episodes (Flory et al. 1998). An intermorbid biological abnormality or trait implies a genetic or developmental origin, although enduring illness or treatment effects cannot be ruled out.Lower serotonergic activity is also independently associated with suicidal behavior. We have hypothesized that there is a serotonergic abnormality contributing to the diathesis or vulnerability for suicidal acts (Mann 1998). Lower levels of CSF 5-HIAA (Åsberg et al. 1986b) and a blunted prolactin response to fenfluramine (Mann et al. 1992) correlate with the presence and lethality of past suicide attempts in patients with major depression and can predict future suicide or suicide attempts (Roy et al. 1989;Träskman-Bendz et al. 1992;Nordström et al. 1994). The association between suicide attempts and low CSF 5-HIAA has also been reported in schizophrenia and personality disorders, indicating that this association is independent of diagnosis. Lower brainstem serotonin (5-HT) and/or 5-hydroxyindoleacetic acid (5-HIAA) levels, and alterations in binding kinetics of a number of serotonin receptor subtypes are reported postmortem in the brain of suicide victims compared...

show abstract

Cerebrospinal fluid monoamine and monoamine metabolite concentrations in melancholia

Cited by 113 publications

References 48 publications

A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment

A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment

Behavioral Actions of Intranasal Application of Dopamine: Effects on Forced Swimming, Elevated Plus-Maze and Open Field Parameters

The Neurobiology and Genetics of Suicide and Attempted Suicide: A Focus on the Serotonergic System

Contact Info

Product

Resources

About