The researchers quantified the transcript levels of GAD67, parvalbumin, somastatin, and Lhx6 in the prefrontal cortex.
GABA or γ (gamma) amino butyric acid is the inhibitory neurotransmitter in our nervous system. That is, it reduces the activity of neurons to which it binds. Interestingly enough, benzodiazepines also bind to GABA receptors, therefore it is believed that GABA’s reducing neuronal activity also reduces anxiety! Hmmmm, will have to look into this! There are also excitatory neurotransmitters in our nervous systems, eg. glutamate, will have to steer well clear of those! Except if in catatonic depression! But seriously…
The study below finds that there are deficits in GABA related molecules such as the GABA synthesizing enzyme GAD67, the calcium binding protein Parvalbumin, the neuropeptide Somatostatin, and the transcription factor Lhx6.
These deficits are most pronounced in a subset of Schizophrenia patients identified as ‘low GABA marker’ or LGM molecular phenotype.
Schizophrenia shares clinical features, possibly genetics, and abnormal cortical circuitry with schizoaffective disorder and bipolar disorder. Therefore they determined to what extent the LGM molecular phenotype was present in these other disorders.
Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype.
They concluded that these findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.
All this research is fascinating, and advances in the field are being made daily. I just can’t wait till some of it is put in to practice for us, the people who have these disorders.
Patients diagnosed with schizophrenia share certain genetic risk factors, as well as clinical features including psychosis and cognitive impairment, with patients diagnosed with either schizoaffective disorder or bipolar disorder.
New evidence indicates that patients diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder can successfully be identified based on their cortical ‘low GABA marker’ (LGM) molecular phenotype. Researchers affiliated with University of Pittsburgh conducted the study, and their findings were published in Psychological Medicine journal.
Postmortem analyses of brain tissue in patients diagnosed with schizophrenia consistently show disturbances in gamma aminobutyric acid (GABA) nerve cells in the prefrontal cortex (PFC). These findings have repeatedly been replicated, and deficits in GABA neuron-related mRNAs cannot be attributed to the use of antipsychotic medications.
“Alterations in inhibitory neurotransmission have been reported to contribute to cognitive impairments that are present in schizophrenia, schizoaffective disorder, and bipolar disorder,” the authors noted in their publication.
In the current study, researchers quantified the transcript levels of GAD67, parvalbumin, somastatin, and Lhx6 in the PFC to identify the cortical phenotype across these 3 severe psychiatric disorders. In line with previous reports, the investigators show that only 5% of typical, healthy control participants (n=87) present with a LGM molecular phenotype, compared with 49% of patients with schizophrenia, 48% of patients with schizoaffective disorder, and 29% of patients with bipolar disorder.
GAD67 is an enzyme that catalyzes the decarboxylation of glutamate to the inhibitory neurotransmitter GABA, and the ablation of GAD67 results in an almost complete reduction in basal GABA levels in the brain. Parvalbumin is a calcium-binding protein present at high levels in GABAergic neurons, and is an important modulator of intracellular calcium dynamics in nerve cells. Somastatin is a cyclic polypeptide that is colocalized and sometimes co-released with GABA, and has been implicated in various cognitive and affective functions. Lhx6 is a transcription factor that is expressed in GABAergic cells and its silencing impedes migration of interneurons into the cortex.
“The presence of the LGM molecular phenotype may represent a substrate for cognitive impairment in subsets of these subjects…. and individuals with [this] phenotype may potentially benefit from pharmacological treatments that focus on GABA-related disturbances,” the authors concluded.
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