Prepulse inhibition in psychiatric disorders – Apart from schizophrenia

Kohl, Sina; Heekeren, Karsten; Klosterkötter, Joachim; Kuhn, Jens

doi:10.1016/j.jpsychires.2012.11.018

Cited by 273 publications

(218 citation statements)

References 87 publications

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“…Future studies could include more sensitive and sophisticated cognitive function tests. Sensory-motor gating as tested by PPI, strongly associated with schizophrenia but less consistently observed in bipolar patients (28,48), was normal in cKO mice. There was dramatic response of key behaviors to lithium and VPA, the classic drugs for human mania.…”

Section: Discussionmentioning

confidence: 85%

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Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder

Zhu

Cordner²,

Xiong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS).We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to "depressionlike" behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.B ipolar disorder and schizophrenia are major psychiatric disorders. Bipolar patients experience both mania, with elevated mood and activity, and depression (often triggered by stress), with low mood and activity. Bipolar disorder is often uniquely responsive to lithium (Li). Many loci have been identified by genome-wide association studies (GWASs) for schizophrenia (1). By contrast, fewer loci with genome-wide significance have been identified for bipolar disorder (2), with some overlap, suggesting some shared mechanisms.In a recent large GWAS of bipolar disorder (3), the most significant signal was detected at the ANK3 locus. This finding has been replicated in many (if not all) GWASs of bipolar disorder (3-5). The ANK3 locus is also found to be associated, to a lesser extent, with schizophrenia (6, 7).The ANK3 gene encodes ankyrin-G, a large scaffold protein highly expressed in neurons in the brain (8). Three main brainspecific splice variants encode 190, 270, and 480 kDa polypeptides. The 480-kDa peptide is the major isoform responsible for organization of the components of the axon initial segment (AIS), including the clustering of voltage-gated sodium and potassium channels important for generation of the action potential (9, 10). The 190-kDa isoform is present at dendritic spines (11,12). Many of the risk alleles for ANK3 are in the five-prime upstream region, suggestive of changes of expression (13, 14). Ankyrin-G protein expression was reduced in pyramidal AISs in superficial layers of schizophrenia cortex (15). These data suggest that ANK3 risk alleles can cause ankyrin-G loss of function.In cortex, the AISs of pyramidal n...

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Section: Discussionmentioning

confidence: 85%

“…PPI deficit is thought to be characteristic of schizophrenia, but less consistently observed in bipolar patients (28). Animal models of schizophrenia typically show deficits in PPI (29).…”

Section: Ank-g Cko Mouse Cortical Pyramidal Neurons Lose Ion Channel mentioning

confidence: 99%

Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder

Zhu

Cordner²,

Xiong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Also, the number and sensitivity of taste papillae is reduced with aging (Morley 1997). Reduced fat intake (and consequently reduced amount of body fat) in the elderly may be partly explained by the fact that fat affects the hedonic qualities of food to a lesser degree compared to younger adults (Kohl et al 2013).…”

Section: Decline Of Sensesmentioning

confidence: 99%

Mechanisms of the anorexia of aging—a review

Wysokiński

Sobów

Kłoszewska

et al. 2015

AGE

189

148

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Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the lack of hunger have been termed as the anorexia of aging. The etiology of the anorexia of aging is multi-factorial and includes a combination of physiological changes associated with aging (decline in smell and taste, reduced central and peripheral drive to eat, delayed gastric emptying), pathological conditions (depression, dementia, somatic diseases, medications and iatrogenic interventions, oral-health status), and social factors (poverty, loneliness). However, exact mechanisms of the anorexia of aging remain to be elucidated. Many neurobiological mechanisms may be secondary to age-related changes in body composition and not associated with anorexia per se. Therefore, further studies on pathophysiological mechanisms of the anorexia of aging should employ accurate measurement of body fat and lean mass. The anorexia of aging is associated with protein-energy malnutrition, sarcopenia, frailty, functional deterioration, morbidity, and mortality. Since this symptom can lead to dramatic consequences, early identification and effective interventions are needed. One of the most important goals in the geriatric care is to optimize nutritional status of the elderly.

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“…In OCD, impaired sensorimotor gating is postulated to cause cortical hyperexcitability and deteriorate inhibitory control, resulting in the inability to inhibit undesired thoughts and images (obsessions) and repetitive acts or reactions to uncontrollable obsessive thoughts (compulsions) (Ahmari et al, 2012;Kohl et al, 2013). CBT improves prepulse inhibition (PPI), an operational index of sensorimotor gating, in other psychiatric conditions (Ahmari et al, 2012;Kumari et al, 2012).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study

Feng

Zhang

Zhu

et al. 2016

Journal of Psychiatric Research

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Background: Transcutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD).Objective: The purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD.Methods: In this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).Results: OCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001).Group B experienced fewer adverse events than the other two groups.Conclusions: TEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD.

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Prepulse inhibition in psychiatric disorders – Apart from schizophrenia

Cited by 273 publications

References 87 publications

Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder

Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder

Mechanisms of the anorexia of aging—a review

Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study

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