Attention serotonin

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

Traditionally, most affective disorders have been treated with compounds that resemble the neurotransmitters that are deficient or in excess in specific brain regions. The aberrant levels of neurotransmitters (or their receptors), such as norepinephrine, dopamine, acetylcholine, and serotonin, have correlated with behavioral symptoms of schizophrenia, depression, anxiety, sleep disorders, motor dysfunctions, attention difficulties, and cognitive disorders. Most drugs discovered for these disorders resulted from screening compounds directly in rodent behavioral models that mimic the behavior of the disease. In these cases, the molecular target" or mechanism of action was assumed to be the deficiency or excess of a neurotransmitter. 

SSRI = selective serotonin reuptake inhibitor SNRI = serotonin norepinephrine reuptake inhibitor ARB = angiotensin receptor blocker ACE = angiotensin converting enzyme COX-2 = cyclooxygenase 2 ADHD = attention deficit hyperactivity disorder. 

Levitan, R. D., Masellis, M., Basile, V. S., et al. (2002) Polymorphism of the serotonin-2A receptor gene (HTR2A) associated with childhood attention deficit hyperactivity disorder (ADHD) in adult women with seasonal affective disorder. J. Ajfect. Disord. 71, 229-233. 

Ickowicz, A., Feng, Y., Wigg, K., et al. (2007) The serotonin receptor HTRIB Gene polymorphisms in attention deficit hyperactivity disorder. Am. J. Med. 144B, 121-125. 

Serotonin-Boosting Antidepressants. Antidepressants that enhance serotonin activity in the brain have also been studied in ADHD. In particular, fluoxetine (Prozac) and the serotonin-selective TCA clomipramine (Anafranil) have been the most extensively evaluated, with mixed success. They provide some benefit for aggression and impulsivity but don t significantly improve the poor attention of ADHD. As a result, the SSRls and other serotonin-boosting antidepressants do not appear to be effective first-line treatments for ADHD. Conversely, depressed patients without ADHD often show improvements in symptoms of concentration and attention when treated with a SSRI. Although SSRls are not widely used in the treatment of ADHD, they may be worthy of consideration in ADHD patients whose impulsivity is not controlled by stimulants alone. Those with comorbid conduct disorder or ODD who are prone to agitation and at times violent outbursts may be helped by the addition of a SSRI. 

SAD, is possibly linked to a decreased serotonin turnover. Such a hypothesis is supported by the fact that the serotonin releasing agent D-fen luramine is effective in treating SAD. Chronobiology is clearly an important area of research for the psychopharmacologist which needs more attention. 

Since no consistent differences in serotonergic catabolism or metabolism have been identified in autism, yet a substantial proportion of autistic people have increased concentrations of platelet serotonin, attention has turned to the platelets themselves. Platelet irregularities may include increased platelet exposure, increased platelet volume or enhanced platelet uptake and storage, of serotonin. By measuring the concentration of plasma free levels of serotonin, it is possible to assess whether the platelet is exposed to elevated lev-... 

The peptide, melatonin, has been implicated in autism. Excess melatonin is thought to decrease learning, memory, attention, emotionality, motivation and pain responses (reviewed Chamberlain Herman, 1990)—all behaviours that are abnormal in autism. Melatonin, released from the pineal gland, is implicated in controlling serotonin and POMC (proopiomelanocortin) peptides, such as beta-endorphin, and an elevation may contribute to, or cause, the serotonin and opioid abnormalities (Chamberlain Herman, 1990). 

The interaction of SSRI agents with other drugs administered breast-feeding women warrants clinical attention. The degree to which SSRI medications are present in breast milk or in infant plasma remains poorly understood (Yoshida et ak, 1999 Burt et ah, 2001). For example, sertraline does not appear at high enough levels in breast-fed infants (n = 11) to alter their platelet serotonin levels (Epperson et ah, 2001). 

A more common approach in difficult to treat cases would be the combination of clomipramine with a SSRI several reports lend support to this practice (Simeon and Thatte, 1990 Figueroa et al., 1998). In this situation, careful attention to the potential pharmacokinetic interactions discussed above are recommended. Sertraline and citalopram are least likely to elevate tricyclic levels due to less potential GYP interactions. By expert consensus, second- (venlafaxine) and third-line (nefazadone and gabapentin) agents may be used when clinical response is inadequate despite a lack of controlled data. Venlafaxine may be substituted for a more typical SSRI while nefazadone or gabapentin may be added to either clomipramine or a SSRI. The combination of venlafaxine with other SSRIs is not generally recommended as it may increase the risk of a serotonin syndrome. The addition of nefazadone to SSRIs presents a lesser risk. 

The mechanism of deprenyl s action is unclear. In addition to enhancing dopaminergic activity in the brain by inhibiting dopamine degradation, deprenyl is metabolized into various stimulant metabolites. In spontaneously hyperactive rats used in an animal model of ADHD, chronic deprenyl administration improved im-pulsivity (but not hyperactivity or attention) along with altering levels of noradrenaline, dopamine, and serotonin and their metabolites (Boix et ah, 1998). 

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