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Anantha Shekhar

Publications and source records attributed to Anantha Shekhar.

32 records · Page 2Linked to original sources
PubMed2004

Neural synchronization deficits to auditory stimulation in bipolar disorder.

Patients with bipolar disorder show cognitive deficits and disorganized behavior, which may reflect a disturbance in neural synchronization. We tested whether EEG measures of auditory neural synchronization were abnormal in bipolar disorder. Nineteen symptomatic patients with bipolar disorder and 32 non-psychiatric control subjects were evaluated. Click trains (500 ms duration) presented at 20, 30, 40 and 50 Hz were used to evoke EEG synchronization. Patients with bipolar disorder showed reduced power across the frequencies of stimulation. Phase-locking across trials was also disturbed in bipolar disorder, consistent with poor phase synchronization between the stimulus and EEG. Abnormal high frequency neural synchronization may contribute to cognitive deficits in bipolar disorder.

Acoustic Stimulation↗
PubMed2004

Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders.

The amygdala is involved in the associative processes for both appetitive and aversive emotions, and its function is modulated by stress hormones. The neuropeptide corticotrophin releasing factor (CRF) is released during stress and has been linked to many stress-related behavioral, autonomic, and endocrine responses. In the present study, nonanxiety-inducing doses of a potent CRF type 1 and 2 receptor agonist, urocortin (Ucn), was infused locally into the basolateral amygdala (BLA) of rats. After 5 daily injections of Ucn, the animals developed anxiety-like responses in behavioral tests. Intravenous administration of the anxiogenic agent sodium lactate elicited robust increases in blood pressure, respiratory rate, and heart rate. Furthermore, in the absence of any additional Ucn treatment, these behavioral and autonomic responses persisted for >30 d. Whole-cell patch-clamp recordings from BLA neurons of these hyper-reactive animals revealed a pronounced reduction in both spontaneous and stimulation-evoked IPSPs, leading to a hyperexcitability of the BLA network. This Ucn-induced plasticity appears to be dependent on NMDA receptor and subsequent calcium-calmodulin-dependent protein kinase II (CaMKII) activation, because it is blocked by pretreatment with NMDA receptor antagonists and by coadministration of CaMKII inhibitors. Our results show for the first time a stress peptide-induced behavioral syndrome that can be correlated with cellular mechanisms of neural plasticity, a novel mechanism that may explain the etiological role of stress in several chronic psychiatric and medical disorders.

Affective Symptoms↗
PubMed2004

Interactions between NPY and CRF in the amygdala to regulate emotionality.

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system and currently there are four known receptor subtypes Y1, Y2, Y4 and Y5. Central NPY and its receptors have been implicated in a variety of physiological processes such as epilepsy, sleep, obesity, learning and memory, gastrointestinal regulation, alcoholism, depression and anxiety. The localization of these receptors within the brain is consistent with the roles mentioned, as they are found in varying density within the limbic structures, such as the hippocampal formation, amygdala, hypothalamus and septum. It is well understood that NPY produces anxiolytic responses following central administration under stressful or anxiety-provoking situations. In contrast, central administration of the neuropeptide corticotropin-releasing factor (CRF) produces anxiogenic behaviors. It has been proposed that NPY counteracts the effects of CRF to maintain no net change in emotional state, e.g., emotional homeostasis. In this article, we review the scientific literature describing the NPY-CRF relationship, specifically as it relates to the modulation of the CRF-mediated stress responses via the amygdala, a key forebrain structure involved in the regulation of emotional states.

Amygdala↗
PubMed2004

Different effects of subchronic doses of 17-beta estradiol in two ethologically based models of anxiety utilizing female rats.

Estrogen may have differing effects on 'anxiety' responses under different conditions. The current study tested the effects of estrogen on anxiety-like behavior when administered for 6-7 days in ovariectomized (OVX) female rats. Two animal paradigms were utilized; the elevated plus maze (EPM), measuring changes in innate fear of exploration of open spaces; and the social interaction test (SIT), measuring the exploration of a novel, same gender partner. In the EPM, estradiol-treated OVX females both entered and spent more time in the open arms than control OVX females, indicating an anxiolytic-like action of estradiol. In contrast, estradiol treated OVX females interacted less with the partner animal in the SIT compared with controls suggesting anxiogenic-like effects. The possible anxiogenic effect of estradiol in the SIT is supported by two findings: (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did not affect locomotion and therefore, the reduced social interaction is not due to reduced activity. Acute administration of progesterone (5 mg/kg), which has anxiolytic properties, did not reverse estradiol-induced social interaction deficits, suggesting that lack of progesterone did not account for estradiol's anxiogenic effects. These results, while seemingly contradictory when interpreted within a unified concept of anxiety, may well reflect the ethological roles of reproductive hormones and their effects on different types of exploratory anxiety.

Alprazolam↗
PubMed2004

Rhabdomyolysis and compartment syndrome with coadministration of risperidone and simvastatin.

We report a case of rhabdomyolysis and acute compartment syndrome of the lower extremity in a schizophrenic patient taking risperidone following the addition of simvastatin to treat hyperlipidemia. We suspect that disrupted drug metabolism, resulting from interactions with cytochrome P450 enzymes, rapidly elevated drug plasma levels, which then led to muscle toxicity. Clinicians who pharmacologically treat medical comorbidities in patients receiving atypical antipsychotics must be proactive in anticipating potential drug-drug interactions.

Acute Disease↗
PubMed2003

The amygdala, panic disorder, and cardiovascular responses.

The amygdala is implicated in a number of emotional responses including conditioned fear and anxiety, and it appears to regulate the behavioral and autonomic responses associated with such emotional responses. The basolateral nucleus of the amygdala (BLA) is under tonic GABAergic inhibition, and acutely blocking this inhibition results in increased anxiety-like behavior, conditioned avoidance, and sympathetically mediated cardiovascular activation. By contrast, activation of the BLA with the stress-related neuropeptide corticotropin-releasing factor results in anxiety-like behavior, but not cardiovascular activation. Furthermore, repeated activation of this region with subthreshold GABA blockade or corticotropin-releasing factor-mediated excitation (priming) results in a chronic anxiety-like state, with susceptibility to panic-like arousal following intravenous lactate infusions. The chronic anxiety state appears to result from a loss of basal inhibitory drive in the BLA as a result of NMDA-dependent synaptic plasticity involving cyclic AMP and calcium calmodulin kinase II (CAM KII)-mediated changes. The lactate-induced panic-like response appears to involve angiotensin-II mediated activation of the BLA. These results suggest that the BLA has a significant role in regulating anxiety, autonomic responses, and the development of anxiety disorders.

Amygdala↗
PubMed2003

Brain imaging studies in mood and anxiety disorders: special emphasis on the amygdala.

Human studies attempting to elucidate brain functioning in health and disease are crucial for our understanding of neuropsychiatric disorders. In the past, scientists relied heavily on neurological lesion studies to understand the functional roles of brain areas. In the last few decades, brain imaging research has made it possible to investigate the molecular and synaptic neuronal events as well as the functioning of neuronal networks in vivo, in patients with neuropsychiatric illnesses. In this context, the functional role of the amygdala has been a focus of neuroimaging studies by leading researchers. Several of these researchers presented papers at a conference, entitled The Amygdala in Brain Function: Basic and Clinical Approaches, that provided the basis for this volume. These papers follow this review in the current volume. The present paper briefly summarizes the highlights of the different presentations, focusing on the functional diversity of the amygdala and its role in different neuropsychiatric disorders; reviews the various brain imaging technologies currently available; and discusses the major findings on the pathophysiology and treatment of depression, bipolar disorder, and anxiety disorders.

Amygdala↗
PubMed2002

Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats.

Disinhibition of neurons in the dorsomedial hypothalamus (DMH) by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) elicits a range of autonomic and endocrine changes resembling those seen in experimental paradigms for emotional stress. Stress in rats is also known to provoke increases in body temperature resulting in part from sympathetically mediated activation of brown fat. The purpose of the present study was to examine the effect of microinjection of BMI into the DMH on core body temperature and temperature of brown fat in rats. In anesthetized preparations, microinjection of BMI 10 pmol/50 nl into the DMH and adjoining posterior hypothalamus elicited marked and rapid increases in temperature in interscapular brown adipose tissue (IBAT) and lesser delayed elevations in rectal temperature. Similar injections into the paraventricular nucleus or ventromedial hypothalamus had no effect on either parameter. Peak increases in IBAT were significantly correlated with both peak increases in core temperature and maximal increases in heart rate that accompanied these changes, and all of these effects were abolished by systemic treatment with propranolol 1 mg/kg. In conscious rats instrumented for telemetry, microinjection of BMI 10 pmol/100 nl into the DMH evoked marked increases in core temperature as well as heart rate, locomotor activity, and plasma ACTH. The increase in core temperature occurred with a delayed time course similar to that seen in anesthetized preparations. These results indicate that activation of neurons in the DMH provokes increases in body temperature resulting in large part from sympathoadrenally-mediated activation of brown fat.

Adipose Tissue, Brown↗
PubMed2002

Amygdala priming results in conditioned place avoidance.

Priming involves daily stimulation of the basolateral nucleus of the amygdala (BLA) for 5 days using a dose of the GABA(A) receptor antagonist, bicuculline methiodide (BMI), that is subthreshold to generate anxiogenic-like responses. The coordinated physiological and behavioral response of the primed rat is similar to the symptoms of human panic disorder and has been used as a model to study panic attacks. If the priming procedure is indeed similar to human panic disorder, then the context in which priming occurs should become associated with aversive conditioning and avoidance as seen in secondary agoraphobia following panic attacks in humans. Therefore, the purpose of this study was to further characterize the behavioral response of priming using the conditioned place avoidance (CPA) task that utilizes distinct tactile cues of a grid floor (Grid+) or hole floor (Grid-). Male Wistar rats (275-300 g) were implanted bilaterally with guide cannulae positioned 1 mm above the BLA. Grid+ animals were placed in the conditioning chamber containing grid floors immediately after a 6-pmol (in 250 nl) BMI injection into the BLA and on hole floors following a sham (250 nl vehicle) injection. Grid animals were placed in the chamber containing hole floors after the BMI injection and on grid floors following the sham injection. Animals were placed in the chamber for 20 min following each injection and injections were separated by 4 h. After 5 days of this treatment, the animals were primed. Two days later, during avoidance testing, each animal was placed in the chamber containing both floors for 30 min. Priming with daily 6-pmol BMI injections into the BLA results in CPA or an aversion to the floor paired with the BMI injection. These results suggest that priming may result in phobic-like responses, similar to the avoidance behavior exhibited by panic disorder patients.

Amygdala↗
PubMed2002

The amygdala and related structures in the pathophysiology of autism.

Autism is a neurodevelopmental disorder that is defined behaviorally by severe deficiencies in reciprocal social interaction, verbal and nonverbal communication, and restricted interests. The amygdala is involved in the regulation of social behaviors and may be an important site of pathology for the social dysfunction seen in autism. This review focuses on lesion, postmortem, and neuroimaging studies that investigate the amygdala and related structures in this disorder. Other brain regions potentially involved in the neuropathology of autism are also briefly discussed. Although supportive evidence exists for amygdala dysfunction in autism, the currently available data are inconsistent and additional research is needed.

Amygdala↗
PubMedDate not supplied

A psychobiological approach to personality: examination within anxious outpatients.

OBJECTIVE: To examine Cloninger's psychobiological personality model among different anxiety and depressive outpatients as well as normal healthy comparisons. In addition, the relationship between the underlying temperament dimensions and behavioral coping strategies was also studied using the tri-axial model of coping. METHODS: Subjects were 120 outpatients presenting to an anxiety disorders specialty clinic and 17 normal comparisons. They underwent a semi-structured clinical interview and completed a battery of questionnaires, including the Temperament and Character Inventory and the Strategic Approach to Coping Scale. RESULTS: On the temperament dimensions, the patients were elevated on the harm avoidance scale relative to the normal comparisons; the temperament substrate was not differentiated by the anxiety or affective diagnostic types nor was there differences between groups on the other temperament dimensions. Both severity of illness and the presence of a comorbid depressive disorder each contributed independently to harm avoidance scores. Hypotheses regarding the association between underlying temperament and behavioral coping strategies were supported for the dimensions of reward dependence and harm avoidance, but not for novelty seeking. CONCLUSIONS: Cloninger's psychobiological model is supported with the temperament of harm avoidance being the relevant dimension for anxiety and affective disorders. The underlying temperament structure also has clinical relevance for the type of coping strategies that are utilized by an individual.

Adult↗
PubMedDate not supplied

Haloperidol impairs learning and error-related negativity in humans.

Humans are able to monitor their actions for behavioral conflicts and performance errors. Growing evidence suggests that the error-related negativity (ERN) of the event-related cortical brain potential (ERP) may index the functioning of this response monitoring system and that the ERN may depend on dopaminergic mechanisms. We examined the role of dopamine in ERN and behavioral indices of learning by administering either 3 mg of the dopamine antagonist (DA) haloperidol (n = 17); 25 mg of diphenhydramine (n = 16), which has a similar CNS profile but without DA properties; or placebo (n = 18) in a randomized, double-blind manner to healthy volunteers. Three hours after drug administration, participants performed a go/no-go Continuous Performance Task, the Eriksen Flanker Task, and a learning-dependent Time Estimation Task. Haloperidol significantly attenuated ERN amplitudes recorded during the flanker task, impaired learning of time intervals, and tended to cause more errors of commission, compared to placebo, which did not significantly differ from diphenhydramine. Drugs had no significant effects on the stimulus-locked P1 and N2 ERPs or on behavioral response latencies, but tended to affect post-error reaction time (RT) latencies in opposite ways (haloperidol decreased and diphenhydramine increased RTs). These findings support the hypothesis that the DA system is involved in learning and the generation of the ERN.

Adult↗