Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding

Abstract

Objectives-Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil ( 123 I Iomazenil). Methods-Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of 123 I Iomazenil. To exclude potential eVects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT. Results-Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no diVerences in r-CBF between groups were found. Catatonic motor and aVective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF. Conclusions-Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations. (J Neurol Neurosurg Psychiatry 1999;67:445-450)

Catatonia in Patients with Autism: Prevalence and Management

“…According to this suggestion, the motor symptoms of catatonia might be caused by a deficiency of cortical gamma-aminobutyric acid (GABA), which acts as the prime inhibitor neurotransmitter. Consequently, this hypothesis can explain the therapeutic effects of benzodiazepines and electroconvulsive therapy (ECT), which cause an increase in GABA activity [9,39,40]. Moreover, it has also been proposed that catatonia and autism may share a common genetic linkage, and, specifically, a common susceptibility region, 15q15-q21, supposed to encode for the c-GABA receptors B3, A5, and G3, in line with the therapeutic effects documented for benzodiazepines in catatonia as well as the role of GABA in ECT [41].…”

Motor Symptoms and Schizophrenia

“…The GABAergic tone within the basal ganglion system further suggests that some motor symptoms may be the result of GABAergic dysfunction in schizophrenia. Dysfunctional GABA transmission has been suggested as a putative cause of some catatonic symptoms such as stupor [128,129,130]. …”

GABAergic dysfunction in mood disorders

“…Neuroimaging studies A recent SPECT study reported abnormally decreased GABA A receptor density in the prefrontal cortex of mood disorder patients, mainly bipolar, with or without akinetic catatonia, 152 a psychomotor syndrome that can be seen in mood disorders and responsive to lorazepam. Recently, a controlled MRS study found abnormally reduced GABA levels in occipital cortex of drug-free depressed patients, without correlation with severity of depression, 153 with a possible normalization after 2 months of selective serotonin reuptake inhibitor (SSRI) treatment.…”

“…This reaction is sensitive to tricyclic antidepressants and electroconvulsive shock therapy (ECST), but not to anxiolytic or major GABA plasma levels kin 40% of depressed, manic, and euthymic mood disorder patients 98,[116][117][118][119][120] 2 in depressed patients 132 GABA enzyme activities kplatelet GABA-T and plasma GAD activities in unipolar and bipolar patients 127,128 Post-mortem studies kGAD activity 130 and mGABA A receptors 141 in the brain of depressed patients k GABA cortical levels with m depression severity in mood disorder patients 151 kexpression of GAD 65 and GAD 67 in prefrontal cortex 148 [141][142][143][144][145][146] Neuroimaging studies kGABA A receptors in the sensory motor cortex of mood disorder patients with akinetic catatonia 152 kGABA occipital cortex levels in depressed patients 153 Neuroendocrine studies (GH response to baclofen ) k in depressed patients 163,164 m in manic patients 161 2 in depressed patients, 162,165,166 Genetic studies Bipolar disorder: association with GABA A receptor a5 (GABRA5) 178 and a3 subunits (GABRA3) 180 possible linkage of GABRA5 and GABA A receptor b1 subunit (GABRB1) loci 181 no association with GABRA1, 179,181,186,188 70,71 Reduced GABA levels in rat nucleus accumbens, brain stem, and cortex have been reported after a session of forced swimming test. 72 Also, muscimol, a GABA agonist, reduced the immobility,...…”