[Biological markers in schizophrenia]

Based on a review of the literature, the article deals with the major biological markers of schizophrenia. Recent developments in molecular biology have shown a possible association between schizophrenia and various HLA markers (A1, A2, A9, A10, A28, B27, BW16), and a linkage--in several families--between the disease and some polymorphisms of chromosome 5. On the other hand, chromosome X might also be involved. Neuropathological abnormalities have often been found in the brains of schizophrenics, such as cellular alterations in the basal ganglia and the limbic structures. Investigations by means of CT-scan and Magnetic Resonance Imaging have pointed out an enlargement of cerebral ventricles and/or an atrophy of frontal areas, especially amongst patients with prominent negative symptoms. The dopaminergic hypothesis of schizophrenia reposes on the major following facts: the therapeutic efficiency of neuroleptics (dopaminergic antagonists); a positive correlation between plasma homovanillic acid (metabolite of dopamine) concentration and the severity of schizophrenic illness; a higher density of dopaminergic D2-receptors (revealed by Positron Emission Tomography thanks to specific radioligands), particularly in the striatum; and an abnormal plasmatic growth-hormone response to apomorphine (dopaminergic agonist). Central noradrenergic dysfunctions might also occur in paranoid schizophrenia, as underlined by higher cerebrospinal fluid levels of norepinephrine, and a lack of decrease of plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG, metabolite of norepinephrine) after clonidine (alpha-2-adrenergic agonist) dispensation. Nevertheless, in patients with predominating negative symptoms, this is a trouble in serotoninergic functions which has been suggested. In the field of immunology, some findings such as alteration in lymphocytes populations (T4/T8, CD5), anti-cerebral auto-antibodies, abnormal lymphocytes responses to mitogens, decreased production of interleukin-2, have lead to two main hypotheses: autoimmunity and immunologic incompetence. On the other hand, electrophysiological studies have shown a hypovariability of alpha-rythm on the EEG; a lower amplitude of the component P300 from visual evoked potentials; sleep disorders such as a shorter rapid eye movement sleep latency and a decreased total slow-wave sleep percent; irregular smooth pursuit eyes-movements; an electrodermal response according to either the hyper-responder either the non-responder type. At last, troubles in sensory integration, motor coordination and attention have also been demonstrated. All those many findings outline the heterogeneity of schizophrenic disorders.