Platelet research in psychiatry

Wirz‐Justice, Anna

doi:10.1007/bf01952199

Cited by 70 publications

(25 citation statements)

References 105 publications

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“…Still, platelets are traditionally used as a peripheral model for neurons and have been shown to reflect brain insults in several neuropsychiatric disorders. 21,22 For example, parallel alterations in brain and platelets were found in imipramine binding of depressed patients and patients who committed suicide, 23 and in complexes I and IV activities in patients with Parkinson's and Alzheimer's diseases, respectively. 24,25 Furthermore, mitochondria have an additional advantage, since they are partly independent organelles containing their own DNA, and their respiratory system is highly preserved along evolution and in different tissues.…”

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confidence: 99%

State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia

et al. 2002

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Keywords: schizophrenia; mitochondrial complex I; human 24-, 51-and 75-kDa subunits of complex I; platelets; biological marker Schizophrenia, the most severe psychiatric disorder, is characterized by heterogeneity of clinical signs, often categorized into positive and negative symptoms. Among a wide array of competing biological mechanisms, altered cerebral energy metabolism and mitochondrial dysfunction have been suggested to play an important role in the pathophysiology of schizophrenia. In this study we investigated mitochondrial complex I in platelets of 113 schizophrenic patients divided into three groups (acute psychotic episode, chronic active state and residual schizophrenia) and 37 control subjects. Complex I was analysed at the level of enzymatic activity, mRNA and protein levels by enzyme kinetics, RT-PCR and Western blot analyses, respectively. Complex I activity in platelets of schizophrenic patients altered with disease state presenting high specificity and sensitivity. Thus, increased activity was associated with psychotic symptomology, while its decrease was observed in patients with residual schizophrenia. The relationship between the clinical state and complex I activity in schizophrenia was further supported by its positive correlation with the severity of patients' positive symptoms assessed by clinical ratings. In addition, similar alterations were observed at the levels of mRNA and protein of the 24-and 51-kDa iron-sulfur flavoprotein subunits of the complex. Taken together these results point to the potential of platelet complex I to turn into a reliable novel marker for schizophrenia. At present, definitive diagnosis depends only on descriptive behavioral and symptomatic information, therefore a peripheral measurable specific marker will contribute to diagnosis and monitoring of the disease. Schizophrenia, is associated with cognitive and emotional decline and a severe reduction in functioning and coping abilities. 1 The heterogeneity and comorbidity with other mental disorders frequently renders schizophrenia difficult to diagnose. 2 Indeed, at present, definitive diagnosis depends only on descriptive behavioral and symptomatic information. Therefore, it is important to develop a biological test for the diagnosis and follow-up of the disorder. The etiology of schizophrenia is still unknown but recent advances in neuroscience have suggested a wide array of competing mechanisms that may be involved in the disorder, 3-6 among them altered cerebral energy metabolism 7 and mitochondria dysfunction. [8][9][10][11][12][13][14] Recently, we have shown that platelet mitochondrial complex I, which is the first complex of the mitochondrial electron transport system, is significantly increased in schizophrenic patients in the acute state, and not in patients with affective disorders. 15 In the present study we further demonstrate that complex I activity is altered with disease state presenting high specificity and sensitivity. In addition, similar alterations were also expressed at the levels of mRN...

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confidence: 99%

State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia

et al. 2002

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“…In addition, alterations in platelet SERT have been observed in many psychiatric disorders and vascular diseases in which 5-HT has been implicated (Meltzer et al, 1981). Therefore, platelets have been widely used as a peripheral indicator of central 5-HT metabolism and SERT function (Wirz-Justice, 1988).Based on a previous study using human embryonic kidney (HEK-293) cells stably transfected with human SERT (hSERT), we reported that activation of PKC and/or inhibi- …”

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confidence: 99%

Evidence for Biphasic Effects of Protein Kinase C on Serotonin Transporter Function, Endocytosis, and Phosphorylation

Jayanthi

Samuvel

Blakely³

et al. 2005

Mol Pharmacol

110

131

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The serotonin transporter (SERT) regulates 5-hydroxytryptamine (serotonin) (5-HT) neurotransmission and is a high-affinity target for antidepressants and psychostimulants. In the present study, we investigated the mechanisms that contribute to a previously unidentified biphasic regulation of endogenous SERTs expressed in the platelets. Treatment of rat platelets with ␤-phorbol 12-myristate 13-acetate (PMA) for 5 min or less resulted in a rapid inhibition of SERT involving changes in intrinsic activity of the transporter (increased K m and decreased V max ). ␤-PMA treatment for 30 min or more produced a sustained inhibition of SERT with a decrease only in the V max . Whereas inhibition of SERT activity was detected from 1 to 45 min after phorbol ester addition, the decrease in surface SERT required at least 30 min of phorbol ester incubation. Increased endocytosis of SERT accounted for the decrease in surface SERT at the later point. Protein kinase C (PKC)-mediated phosphorylation of SERT occurs on the plasma membrane during the initial phase of rapid transporter inhibition, and later, the phosphorylated SERT enters the intracellular pool. ␤-PMA-induced phosphorylation of SERT occurs initially on serine residues(s) and then on threonine residue(s). The initial serine phosphorylation corresponded to the first phase of rapid inhibition mediated by changes in intrinsic activity and/or silencing of SERT. The later phosphorylation on threonine residue(s) corresponded to the later phase of sustained inhibition mediated by an enhanced endocytosis of SERT. Together, these data reveal that in platelets, SERT function is regulated by PKC in a biphasic manner involving both trafficking-dependent and independent mechanisms and that these two events occur at distinct phases of transporter phosphorylation.5-Hydroxytryptamine (serotonin; 5-HT) controls many behavioral and physiological functions (Jacobs and Fornal, 1995). 5-HT uptake via the cocaine-and antidepressantsensitive serotonin transporter (SERT) is essential for serotonergic neurotransmission termination (Barker and Blakely, 1995). Altered SERT expression and two polymorphic regions in SERT promoter have been implicated in multiple forms of psychopathology, including depression, suicide, anxiety, aggression, schizophrenia, alcoholism, and drug addiction (Murphy et al., 2004). Although clearance of synaptic and extrasynaptic 5-HT seems to be the principal function of SERTs, certain cells, notably platelets, use SERTs to acquire 5-HT from the extracellular environment for subsequent release, involving in the processes of platelet activation (Cirillo et al., 1999). Platelets and 5-HT neurons share many common properties, including vesicular monoamine transporters, 5-HT release, biochemistry, identical SERT sequences, and 5-HT receptors (Owens and Nemeroff, 1994). In addition, alterations in platelet SERT have been observed in many psychiatric disorders and vascular diseases in which 5-HT has been implicated (Meltzer et al., 1981). Therefore, platelets have been w...

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“…A significant reduction in neuronal membrane viscosity should thus lead to a commensurate reduction of serotonin. This would explain similarities between neurons and platelets in major depression (Takahashi, 1976;Edwards, 1978;Marangos, 1979;Kim, 1982;Rotman, 1983;Dreux, 1985;Wirz-Justice, 1988;Camacho, 2000;Plein, 2001;MaurerSpurej, 2007).…”

Section: Quantitative and Quantum Approaches To Psychopathologymentioning

confidence: 99%

Consciousness and Hallucinations: Molecular Considerations and Theoretical Questions

et al. 2011

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This paper focuses on aspects of quantitative and quantum approaches to the phenomenon of hallucination. Consideration is given to the molecular hypothesis of consciousness, to consciousness as perception of the self, and to hallucinatory perception as consciousness detached from reality. The possible transitional sequence viscosity of membrane / GS-alpha protein / tubulin in altered states of consciousness is explored.

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Platelet research in psychiatry

Cited by 70 publications

References 105 publications

State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia

State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia

Evidence for Biphasic Effects of Protein Kinase C on Serotonin Transporter Function, Endocytosis, and Phosphorylation

Consciousness and Hallucinations: Molecular Considerations and Theoretical Questions

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