Role of cortical interneurons in pathogenesis of schizophrenia

Shizofrenija je psihijatrijska bolest koja se manifestira raznim simptomima poput deluzija, halucinacija i socijalnog udaljavanja. Iako je istraživački interes oko shizofrenije velik, te se u zadnjih nekoliko godina javio velik napredak u znanosti i tehnikama proučavanja mozga, znanstvenici i dalje nisu uspjeli definirati točne mehanizme nastanka shizofrenije. Jedan od potencijalnih mehanizama patogeneze shizofrenije je disfunkcija kortikalnih interneurona, odnosno disfunkcija sustava glavnog interneurona kojeg oni luče – gama-aminomaslačne kiseline (GABA-e). Studije rađene na osobama oboljelim od shizofrenije pružaju razne nalaze koji bi podupirali hipotezu da disfunkcija kortikalnih interneurona vodi raznim mehanizmima do razvoja shizofrenije. Nađen je smanjen broj sinapsi na tijelima kortikalnih interneurona (smanjen je input), nađena je manja količina enzima koji sintetiziraju GABA-u kao i njihove kodirajuće mRNA. Također su nađene i promijenjene količine GABA receptora u sinapsama koje kortikalni interneuroni čine (smanjen im je output). Slikovne metode prikaza mozga također ukazuju na određene abnormalnosti što se tiče morfologije, ali i funkcije određenih moždanih regija kod osoba oboljelih od shizofrenije. Takva saznanja bi jednog dana mogla imati klinički značaj u smislu detekcije patološki promijenjenih regija mozga koje bi trebale biti mjesto ciljane terapije.Schizophrenia is a psychiatric disease that manifests with various symptoms, such as delusions, hallucinations and social withdrawal. Although research interest in schizophrenia is high, scientists are still unable to define exact mechanisms that lead to the development of the disease, in spite of breakthroughs in scientific methods. One of the potential pathogenetic mechanisms involves dysfunction of cortical inter-neurons, more precisely dysfunction of their main neurotransmitter – gamma-aminobutyric acid (GABA). Studies performed on patients suffering from schizophrenia offer some evidence that support the hypothesis that dysfunction of cortical interneurons leads to development of schizophrenia through various mechanisms. Decreased number of synapses on the membrane of cortical interneurons was found (lower input), followed with the decreased number of enzymes that lead to the GABA production as well as their encoding mRNA. Moreover, a decrease in GABA receptor density was found in synapses involving cortical interneurons (decreased output). Imaging methods also provide findings of abnormalities in both morphology and function of several regions of the brain in patients suffering schizophrenia. Such findings could potentially have therapeutic value in the future in means of highlighting pathological regions of the brain that should be a therapeutic target

Role of cortical interneurons in pathogenesis of schizophrenia

Shizofrenija je psihijatrijska bolest koja se manifestira raznim simptomima poput deluzija, halucinacija i socijalnog udaljavanja. Iako je istraživački interes oko shizofrenije velik, te se u zadnjih nekoliko godina javio velik napredak u znanosti i tehnikama proučavanja mozga, znanstvenici i dalje nisu uspjeli definirati točne mehanizme nastanka shizofrenije. Jedan od potencijalnih mehanizama patogeneze shizofrenije je disfunkcija kortikalnih interneurona, odnosno disfunkcija sustava glavnog interneurona kojeg oni luče – gama-aminomaslačne kiseline (GABA-e). Studije rađene na osobama oboljelim od shizofrenije pružaju razne nalaze koji bi podupirali hipotezu da disfunkcija kortikalnih interneurona vodi raznim mehanizmima do razvoja shizofrenije. Nađen je smanjen broj sinapsi na tijelima kortikalnih interneurona (smanjen je input), nađena je manja količina enzima koji sintetiziraju GABA-u kao i njihove kodirajuće mRNA. Također su nađene i promijenjene količine GABA receptora u sinapsama koje kortikalni interneuroni čine (smanjen im je output). Slikovne metode prikaza mozga također ukazuju na određene abnormalnosti što se tiče morfologije, ali i funkcije određenih moždanih regija kod osoba oboljelih od shizofrenije. Takva saznanja bi jednog dana mogla imati klinički značaj u smislu detekcije patološki promijenjenih regija mozga koje bi trebale biti mjesto ciljane terapije.Schizophrenia is a psychiatric disease that manifests with various symptoms, such as delusions, hallucinations and social withdrawal. Although research interest in schizophrenia is high, scientists are still unable to define exact mechanisms that lead to the development of the disease, in spite of breakthroughs in scientific methods. One of the potential pathogenetic mechanisms involves dysfunction of cortical inter-neurons, more precisely dysfunction of their main neurotransmitter – gamma-aminobutyric acid (GABA). Studies performed on patients suffering from schizophrenia offer some evidence that support the hypothesis that dysfunction of cortical interneurons leads to development of schizophrenia through various mechanisms. Decreased number of synapses on the membrane of cortical interneurons was found (lower input), followed with the decreased number of enzymes that lead to the GABA production as well as their encoding mRNA. Moreover, a decrease in GABA receptor density was found in synapses involving cortical interneurons (decreased output). Imaging methods also provide findings of abnormalities in both morphology and function of several regions of the brain in patients suffering schizophrenia. Such findings could potentially have therapeutic value in the future in means of highlighting pathological regions of the brain that should be a therapeutic target

Cortical interneurons in schizophrenia – cause or effect?

GABAergic cortical interneurons are important components of cortical microcircuits. Their alterations are associated with a number of neurological and psychiatric disorders, and are thought to be especially important in the pathogenesis of schizophrenia. Here, we reviewed neuroanatomical and histological studies that analyzed different populations of cortical interneurons in postmortem human tissue from patients with schizophrenia and adequately matched controls. The data strongly suggests that in schizophrenia only selective interneuron populations are affected, with alterations of somatostatin and parvalbumin neurons being the most convincing. The most prominent changes are found in the prefrontal cortex, which is consistent with the impairment of higher cognitive functions characteristic of schizophrenia. In contrast, calretinin neurons, the most numerous interneuron population in primates, seem to be largely unaffected. The selective alterations of cortical interneurons are in line with the neurodevelopmental model and the multiple-hit hypothesis of schizophrenia. Nevertheless, a large number of data on interneurons in schizophrenia is still inconclusive, with different studies yielding opposing findings. Furthermore, no studies found a clear link between interneuron alterations and clinical outcomes. Future research should focus on the causes of changes in the cortical microcircuitry in order to identify potential therapeutic targets